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Los Angeles, CA, United States

The University of Southern California is a private, not-for-profit, nonsectarian, research university founded in 1880 with its main campus in the city area of Los Angeles, California. As California's oldest private research university, USC has historically educated a large number of the region's business leaders and professionals. In recent decades, the university has also leveraged its location in Los Angeles to establish relationships with research and cultural institutions throughout Asia and the Pacific Rim. In 2011, USC was named among the Top 10 Dream Colleges in the nation. It holds a vast array of trademarks and wordmarks to the term "USC."For the 2012-2013 academic year, there were 18,316 students enrolled in four-year undergraduate programs. USC is also home to 21,642 graduate and professional students in a number of different programs, including business, law, social work, and medicine. The university has a "very high" level of research activity and received $560.9 million in sponsored research from 2009 to 2010. USC sponsors a variety of intercollegiate sports and competes in the National Collegiate Athletic Association as a member of the Pacific-12 Conference. Members of the sports teams, the Trojans, have won 100 NCAA team championships, ranking them third in the nation, and 378 NCAA individual championships, ranking them second in the nation. Trojan athletes have won 287 medals at the Olympic games , more than any other university in the world. If USC were a country, it would rank 12th in most Olympic gold medals. Wikipedia.


Boyd P.W.,University of Otago | Hutchins D.A.,University of Southern California
Marine Ecology Progress Series | Year: 2012

Oceanic conditions are changing at an unprecedented rate, and these anthropogenically driven changes will intensify into the future. The marine biota will encounter a complex shifting matrix of simultaneous environmental changes - including temperature, pH/pCO2, nutrients, light, and oxygen - which will be further compounded by concurrent regional and local anthropogenic impacts, such as altered freshwater runoff regimes or biomass harvesting. We are only beginning to grasp the complexity of these interactive changes on ocean biota. To understand the pronounced and/or nonlinear effects of cumulative environmental stresses on organismal fitness and ecosystem functioning, the marine global-change research community can profit from the large body of existing evidence from freshwater lakes or polluted aquatic systems. We explore how the complex environmental changes will affect the biota from primary producers to higher trophic levels in both nearshore and open ocean waters, and conclude by proposing new approaches to address the formidable challenges of this research field. This Theme Section on 'Biological responses in an anthropogenically modified ocean' presents a set of papers that highlights the multiplicity of factors that will alter major biogeochemical and ecological frameworks, and raises awareness of the complexities involved in disentangling the combined effects of global, regional and local anthropogenic change on marine food webs. © Inter-Research 2012.


Lane B.R.,Michigan State University | Campbell S.C.,Cleveland Clinic | Gill I.S.,University of Southern California
Journal of Urology | Year: 2013

Purpose: Open partial nephrectomy has proven long-term oncologic efficacy. Laparoscopic partial nephrectomy outcomes at 5 to 7 years of followup appear comparable to those of the open approach. We present the 10-year outcomes of patients who underwent laparoscopic or open partial nephrectomy for a single clinical stage cT1 7 cm or less renal cortical tumor. Materials and Methods: Of 1,541 patients treated with partial nephrectomy for a single cT1 tumor between 1999 and 2007 with a minimum 5-year followup, an actual followup of 10 years or greater was available in 45 and 254 after laparoscopic and open partial nephrectomy, respectively. Results: Median followup after laparoscopic and open surgery was 6.6 and 7.8 years, respectively. At 10 years the overall survival rate was 77.2%. The metastasis-free survival rate was 95.2% and 90.0% after partial nephrectomy for clinical T1a and T1b renal cell carcinoma, respectively (p <0.0001). Baseline differences between patients treated with laparoscopic and open partial nephrectomy accounted for most observed differences between the cohorts. The median glomerular filtration rate decrease was 16.9% after the laparoscopic approach and 14.1% after the open approach (p = 0.5). On multivariable analysis predictors of all cause mortality included advancing age (HR 1.52/10 years, p <0.0001), comorbidity (HR 1.33/1 U, p <0.0001), absolute indication (HR 2.25, p = 0.003) and predicted recurrence-free survival (HR 1.58/10% increased risk, p = 0.004) but not laparoscopic vs open operative approach (p = 0.13). Similarly, predictors of metastasis included absolute indication (HR 4.35, p <0.0001) and predicted recurrence-free survival (HR 2.67, p <0.0001) but not operative approach (p = 0.42). Conclusions: The 10-year outcomes of laparoscopic nephrectomy and open partial nephrectomy are excellent in carefully selected patients with limited risk of recurrence for cT1 renal cortical tumors. Overall survival at 10 years is mediated by patient factors such as age, comorbidity and operative indication, and by cancer factors such as predicted recurrence-free survival but not by the choice of operative technique, which depends on surgeon preference and experience. © 2013 American Urological Association Education and Research, Inc.


Kim H.,University of Southern California
Nature communications | Year: 2013

Wnt/β-catenin signalling has a variety of roles in regulating stem cell fates. Its specific role in mouse epiblast stem cell self-renewal, however, remains poorly understood. Here we show that Wnt/β-catenin functions in both self-renewal and differentiation in mouse epiblast stem cells. Stabilization and nuclear translocation of β-catenin and its subsequent binding to T-cell factors induces differentiation. Conversely, retention of stabilized β-catenin in the cytoplasm maintains self-renewal. Cytoplasmic retention of β-catenin is effected by stabilization of Axin2, a downstream target of β-catenin, or by genetic modifications to β-catenin that prevent its nuclear translocation. We also find that human embryonic stem cell and mouse epiblast stem cell fates are regulated by β-catenin through similar mechanisms. Our results elucidate a new role for β-catenin in stem cell self-renewal that is independent of its transcriptional activity and will have broad implications in understanding the molecular regulation of stem cell fate.


Lin W.,Nanyang Technological University | Jay Kuo C.-C.,University of Southern California
Journal of Visual Communication and Image Representation | Year: 2011

Visual quality evaluation has numerous uses in practice, and also plays a central role in shaping many visual processing algorithms and systems, as well as their implementation, optimization and testing. In this paper, we give a systematic, comprehensive and up-to-date review of perceptual visual quality metrics (PVQMs) to predict picture quality according to human perception. Several frequently used computational modules (building blocks of PVQMs) are discussed. These include signal decomposition, just-noticeable distortion, visual attention, and common feature and artifact detection. Afterwards, different types of existing PVQMs are presented, and further discussion is given toward feature pooling, viewing condition, computer-generated signal and visual attention. Six often-used image metrics (namely SSIM, VSNR, IFC, VIF, MSVD and PSNR) are also compared with seven public image databases (totally 3832 test images). We highlight the most significant research work for each topic and provide the links to the extensive relevant literature. © 2011 Elsevier Inc. All rights reserved.


Background: As quality-adjusted life years have become the standard metric in health economic evaluations, mapping health-profile or disease-specific measures onto preference-based measures to obtain quality-adjusted life years has become a solution when health utilities are not directly available. However, current mapping methods are limited due to their predictive validity, reliability, and/or other methodological issues. Objectives: We employ probability theory together with a graphical model, called a Bayesian network, to convert health-profile measures into preference-based measures and to compare the results to those estimated with current mapping methods. Methods: A sample of 19,678 adults who completed both the 12-item Short Form Health Survey (SF-12v2) and EuroQoL 5D (EQ-5D) questionnaires from the 2003 Medical Expenditure Panel Survey was split into training and validation sets. Bayesian networks were constructed to explore the probabilistic relationships between each EQ-5D domain and 12 items of the SF-12v2. The EQ-5D utility scores were estimated on the basis of the predicted probability of each response level of the 5 EQ-5D domains obtained from the Bayesian inference process using the following Methods: Monte Carlo simulation, expected utility, and most-likely probability. Results were then compared with current mapping methods including multinomial logistic regression, ordinary least squares, and censored least absolute deviations. Results: The Bayesian networks consistently outperformed other mapping models in the overall sample (mean absolute error=0.077, mean square error=0.013, and R overall=0.802), in different age groups, number of chronic conditions, and ranges of the EQ-5D index. Conclusion: Bayesian networks provide a new robust and natural approach to map health status responses into health utility measures for health economic evaluations. © 2011 Lippincott Williams & Wilkins.


Schonthal A.H.,University of Southern California
Anti-Cancer Agents in Medicinal Chemistry | Year: 2010

Cyclooxygenase 2 (COX-2) is frequently found up-regulated during pathological conditions and in cancer, where it is thought to support carcinogenesis and tumor angiogenesis. The development of newer-generation non-steroidal anti-inflammatory drugs (NSAIDs) able to more selectively inhibit cyclooxygenase 2 (COX-2) raised expectations that these agents might be beneficial for cancer prevention and therapy. However, while chemopreventive effects of some selective COX-2 inhibitors have been established, it has remained unpersuasive whether these new NSAIDs, such as celecoxib, rofecoxib or etoricoxib, are able to exert cancer therapeutic effects*i.e., whether they would be beneficial for the treatment of advanced cancers that are already grown and established. This issue was further complicated by findings that celecoxib was able to exert pronounced pro-apoptotic effects in vitro and in vivo in the absence of any apparent involvement of COX-2. In fact, newly synthesized close structural analogs of the celecoxib molecule revealed that it was possible to separate COX-2 inhibitory function from the ability to trigger apoptosis; for example, the analog 2,5-dimethyl-celecoxib (DMC) has lost COX-2 inhibitory function, yet exerts increased cytotoxic potency. This review will summarize pertinent results from the exploratory therapeutic use of NSAIDs, in particular celecoxib, in preclinical and clinical studies of malignant glioma. Several COX-2 independent targets will be presented, and it will be discussed how DMC has helped to delineate their relevance for the surmised COX-2 independent tumoricidal effects of celecoxib. © 2010 Bentham Science Publishers Ltd.


Powers C.M.,University of Southern California
The Journal of orthopaedic and sports physical therapy | Year: 2012

Patellofemoral pain (PFP) is one of the most common lower extremity conditions seen in orthopaedic practice. The mission of the second International Patellofemoral Pain Research Retreat was to bring together scientists and clinicians from around the world who are conducting research aimed at understanding the factors that contribute to the development and, consequently, the treatment of PFP. The format of the 2.5-day retreat included 2 keynote presentations, interspersed with 6 podium and 4 poster sessions. An important element of the retreat was the development of consensus statements that summarized the state of the research in each of the 4 presentation categories. In this supplement, you will find the consensus documents from the meeting, as well as the keynote addresses, schedule, and platform and poster presentation abstracts.


Ailshire J.A.,University of Southern California | Burgard S.A.,University of Michigan
Journal of Health and Social Behavior | Year: 2012

Sleep is essential for health and daily functioning, and social relationships may be a key social factor influencing sleep, yet sleep has been understudied in the literature on social relationships and health. This study used data from the National Survey of Midlife Development in the United States to examine associations between troubled sleep and family contact, social support, and strain. Results show that having strained family relationships is associated with more troubled sleep, while supportive family relationships are associated with less troubled sleep. Family strain is more consequential for sleep than support, and sleep troubles are greatest when family relationships are highly strained and provide inadequate emotional support. Family strain is also more harmful to sleep among individuals who are in frequent contact with family members. These findings underscore the importance of focusing on both negative and positive aspects of relationships and highlight the significance of family relationships for sleep. © American Sociological Association 2012.


Staurenghi G.,University of Milan | Sadda S.,University of Southern California | Chakravarthy U.,Queens University of Belfast | Spaide R.F.,Vitreous Retina Macula Consultants of New York
Ophthalmology | Year: 2014

Purpose To develop a consensus nomenclature for the classification of retinal and choroidal layers and bands visible on spectral-domain optical coherence tomography (SD-OCT) images of a normal eye. Design An international panel with expertise in retinal imaging (International Nomenclature for Optical Coherence Tomography [IN•OCT] Panel) was assembled to define a consensus for OCT imaging terminology. Participants A panel of retina specialists. Methods A set of 3 B-scan images from a normal eye was circulated to the panel before the meeting for independent assignment of nomenclature to anatomic landmarks in the vitreous, retina, and choroid. The outputs were scrutinized, tabulated, and used as the starting point for discussions at a roundtable panel meeting. The history of anatomic landmark designations over time was reviewed for the various cellular layers of the ocular structures that are visible by SD-OCT. A process of open discussion and negotiation was undertaken until a unanimous consensus name was adopted for each feature. Main Outcome Measures Definitions of normal eye features showed by SD-OCT. Results Definitions for various layers changed frequently in the literature and were often inconsistent with retinal anatomy and histology. The panel introduced the term "zone" for OCT features that seem to localize to a particular anatomic region that lacks definitely proven evidence for a specific reflective structure. Such zones include the myoid, ellipsoid, and the interdigitation zones. Conclusions A nomenclature system for normal anatomic landmarks seen on SD-OCT outputs has been proposed and adopted by the IN•OCT Panel. The panel recommends this standardized nomenclature for use in future publications. The proposed harmonizing of terminology serves as a basis for future OCT research studies. © 2014 by the American Academy of Ophthalmology.


Neely M.J.,University of Southern California
Proceedings - IEEE INFOCOM | Year: 2011

We first consider a multi-user, single-hop wireless network with arbitrarily varying (and possibly non-ergodic) arrivals and channels. We design an opportunistic scheduling algorithm that guarantees all sessions have a bounded worst case delay. The algorithm has no knowledge of the future, but yields throughput-utility that is close to (or better than) that of a T-slot lookahead policy that makes "ideal" decisions based on perfect knowledge up to T slots into the future. We then extend the algorithm to treat worst case delay guarantees in multi-hop networks. Our analysis uses a sample-path version of Lyapunov optimization together with a novel virtual queue structure. © 2011 IEEE.


Young G.,University of Southern California
Haemophilia | Year: 2012

Haemophilia is a life-long genetic disorder most often diagnosed in early childhood which results in bleeding into deep tissues and can result in arthropathy and, rarely, other serious complications. As a result of the natural physical and cognitive development in children, combined with the manner in which haemophilia is treated, there is a continuous process of changes in the approach to patient management, which collectively are called transitional issues. It is important to point out that while some traditional definitions of transition are limited to the stage when an adolescent becomes an adult and how the mode and delivery of care change during this time, a broader definition incorporating all the changes that occur from birth through adulthood will be described in this article. As such, transition should be thought of as a continuous process, though for the sake of clarity and practicality, we will divide the process into several phases. The transition issues to be discussed will be divided into medical issues and psychosocial issues, though there is clearly overlap between the two. A well-developed transition plan from birth to adulthood for patients with haemophilia facilitates the necessary change from total dependence on caregivers to complete independence by the time one reaches 18years of age. © 2012 Blackwell Publishing Ltd.


West J.R.,HRL Laboratories | Fong B.H.,HRL Laboratories | Lidar D.A.,University of Southern California
Physical Review Letters | Year: 2010

We present a near-optimal quantum dynamical decoupling scheme that eliminates general decoherence of a qubit to order n using O(n2) pulses, an exponential decrease in pulses over all previous decoupling methods. Numerical simulations of a qubit coupled to a spin bath demonstrate the superior performance of the new pulse sequences. © 2010 The American Physical Society.


Tilson J.K.,University of Southern California
BMC Medical Education | Year: 2010

Background: Health care educators need valid and reliable tools to assess evidence based practice (EBP) knowledge and skills. Such instruments have yet to be developed for use among physical therapists. The Fresno Test (FT) has been validated only among general practitioners and occupational therapists and does not assess integration of research evidence with patient perspectives and clinical expertise. The purpose of this study was to develop and validate a modified FT to assess EBP knowledge and skills relevant to physical therapist (PT) practice. Methods: The FT was modified to include PT-specific content and two new questions to assess integration of patient perspectives and clinical expertise with research evidence. An expert panel reviewed the test for content validity. A cross-sectional cohort representing three training levels (EBP-novice students, EBP-trained students, EBP-expert faculty) completed the test. Two blinded raters, not involved in test development, independently scored each test. Construct validity was assessed through analysis of variance for linear trends among known groups. Inter and intra-rater reliability, internal consistency, item discrimination index, item total correlation, and difficulty were analyzed. Results: Among 108 participants (31 EBP-novice students, 50 EBP-trained students, and 27 EBP-expert faculty), there was a statistically significant (p < 0.0001) difference in total score corresponding to training level. Total score reliability and psychometric properties of items modified for discipline-specific content were excellent [inter-rater (ICC (2,1)] = 0.91); intra-rater (ICC (2,1)] = 0.95, 0.96)]. Cronbach's was 0.78. Of the two new items, only one had strong psychometric properties. Conclusions: The 13-item modified FT presented here is a valid, reliable assessment of physical therapists' EBP knowledge and skills. One new item assesses integration of patient perspective as part of the EBP model. Educators and researchers may use the 13-item modified FT to evaluate PT EBP curricula and physical therapists' EBP knowledge and skills. © 2010 Tilson; licensee BioMed Central Ltd.


Sleight A.,University of Southern California
Disability and Rehabilitation | Year: 2016

Purpose: Cancer-related cognitive dysfunction (CRCD) impacts memory, attention, concentration, language, multi-tasking, and organizational skills and decreases participation and quality of life for cancer survivors. The objectives of this article are: (1) to outline the neuroscience of CRCD, its risk factors, and its effect on participation; and (2) to identify and summarize the literature on rehabilitation interventions and coping techniques for CRCD in cancer survivors. Methods: A scoping review of articles cited in PubMed, MEDLINE, PsychINFO, and CINAHL was performed. To be included, articles must have been published in a peer-reviewed scientific journal between 1996 and 2014, written in English, and included a quantitative or qualitative non-pharmacological study of interventions and/or coping strategies for adult cancer survivors experiencing CRCD. Results: Ten articles met the inclusion criteria for final review. Six studies tested the efficacy of rehabilitation treatments on CRCD. Three involved cognitive-behavioral therapy (CBT), while three tested neuropsychological and/or cognitive training interventions. Four qualitative studies investigated coping strategies used by survivors with CRCD. Conclusions: CBT-based treatments and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most commonly-reported coping strategy is utilization of assistive technology and memory aids. Further research is needed about efficacious rehabilitation techniques for this population.Implications for RehabilitationCancer-related cognitive dysfunction (CRCD) may impact up to 50% of cancer survivors.CRCD can significantly decrease participation and quality of life during survivorship.Cognitive-behavioral therapy (CBT) and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD.The most common coping strategy reported by cancer survivors with CRCD is the use of assistive technology and memory aids. © 2015 Informa UK Ltd.


Wood J.N.,University of Southern California
Psychological Science | Year: 2014

For an organism to perceive coherent and unified objects, its visual system must bind color and shape features into integrated color-shape representations in memory. However, the origins of this ability have not yet been established. To examine whether newborns can build an integrated representation of the first object they see, I raised newly hatched chicks (Gallus gallus) in controlled-rearing chambers that contained a single virtual object. This object rotated continuously, revealing a different color and shape combination on each of its two faces. Chicks were able to build an integrated representation of this object. For example, they reliably distinguished an object defined by a purple circle and yellow triangle from an object defined by a purple triangle and yellow circle. This result shows that newborns can begin binding color and shape features into integrated representations at the onset of their experience with visual objects. © The Author(s) 2014.


BACKGROUND:: This study was designed to evaluate SERI Surgical Scaffold (SERI), a silk-derived bioresorbable scaffold, in an ovine model of two-stage breast reconstruction.METHODS:: Sheep were bilaterally implanted with either SERI or sham [sutures] during the stage 1 procedure. The SERI group underwent an exchange procedure for a breast implant at 3 months; animals in the sham group were sacrificed at 3 months.RESULTS:: The sham samples were significantly weaker than the SERI+tissue samples by 3 months. At all endpoints, SERI+tissue samples were ≥ 150% of native ovine fascial strength. Histological evaluation of SERI samples showed evidence of bioresorption through 12 months.CONCLUSIONS:: SERI provided adequate soft tissue support with progressive bioresorption. By 12 months, newly formed tissue had assumed the majority of load-bearing responsibility.LEVEL OF EVIDENCE:: N/A – animal study. ©2014American Society of Plastic Surgeons


Miller M.S.,University of Southern California | Eaton D.W.,University of Calgary
Geophysical Research Letters | Year: 2010

Delineating mantle interfaces can provide important clues for understanding the formation of continents. We use S-wave receiver functions to investigate lithospheric structure along a transect extending from Vancouver Island to Baffin Island. Observed Sp converted waves allow for interpretation of boundaries in the depth range expected for tectonic plates. Receiver functions show a distinct negative amplitude feature, interpreted as the lithosphere-asthenosphere boundary, at shallow depths beneath British Columbia (∼85km), deepening abruptly at the eastern edge of the Cordillera to ∼260km beneath the Canadian Shield. Dipping mid-lithospheric discontinuities extend beneath several giant ca. 1.8 Ga epicontinental magmatic arcs, consistent with formation of cratonic lithosphere by arc accretion. This model provides a plausible explanation for global mid-lithospheric discontinuities within cratons and aids in understanding their formation. © 2010 by the American Geophysical Union.


Mendel J.M.,University of Southern California
IEEE Transactions on Fuzzy Systems | Year: 2014

The purpose of this tutorial paper is to make general type-2 fuzzy logic systems (GT2 FLSs) more accessible to fuzzy logic researchers and practitioners, and to expedite their research, designs, and use. To accomplish this, the paper 1) explains four different mathematical representations for general type-2 fuzzy sets (GT2 FSs); 2) demonstrates that for the optimal design of a GT2 FLS, one should use the vertical-slice representation of its GT2 FSs because it is the only one of the four mathematical representations that is parsimonious; 3) shows how to obtain set theoretic and other operations for GT2 FSs using type-1 (T1) FS mathematics (α - cuts play a central role); 4) reviews Mamdani and TSK interval type-2 (IT2) FLSs so that their mathematical operations can be easily used in a GT2 FLS; 5) provides all of the formulas that describe both Mamdani and TSK GT2 FLSs; 6) explains why center-of sets type-reduction should be favored for a GT2 FLS over centroid type-reduction; 7) provides three simplified GT2 FLSs (two are for Mamdani GT2 FLSs and one is for a TSKGT2 FLS), all of which bypass type reduction and are generalizations from their IT2 FLS counterparts to GT2 FLSs; 8) explains why gradient-based optimization should not be used to optimally design a GT2 FLS; 9) explains how derivative-free optimization algorithms can be used to optimally design a GT2 FLS; and 10) provides a three-step approach for optimally designing FLSs in a progressive manner, from T1 to IT2 to GT2, each of which uses a quantum particle swarm optimization algorithm, by virtue of which the performance for the IT2 FLS cannot be worse than that of the T1 FLS, and the performance for the GT2 FLS cannot be worse than that of the IT2 FLS. © 2013 IEEE.


Huang L.,Tsinghua University | Neely M.J.,University of Southern California
IEEE/ACM Transactions on Networking | Year: 2013

In this paper, we show how to achieve close-to-optimal utility performance in energy-harvesting networks with only finite capacity energy storage devices. In these networks, nodes are capable of harvesting energy from the environment. The amount of energy that can be harvested is time-varying and evolves according to some probability law. We develop an online algorithm, called the Energy-limited Scheduling Algorithm (ESA), which jointly manages the energy and makes power allocation decisions for packet transmissions. ESA only has to keep track of the amount of energy left at the network nodes and does not require any knowledge of the harvestable energy process. We show that ESA achieves a utility that is within O(ε) of the optimal, for any ε>0, while ensuring that the network congestion and the required capacity of the energy storage devices are deterministically upper-bounded by bounds of size O(1/ε). We then also develop the Modified-ESA (MESA) algorithm to achieve the same O(ε) close-to-utility performance, with the average network congestion and the required capacity of the energy storage devices being only O(log (1/ε)]2) , which is close to the theoretical lower bound O(log (1/ε)). © 1993-2012 IEEE.


Neely M.J.,University of Southern California
IEEE Transactions on Automatic Control | Year: 2013

This paper considers optimization of time averages in systems with variable length renewal frames. Applications include power-aware and profit-aware scheduling in wireless networks, peer-to-peer networks, and transportation systems. Every frame, a new policy is implemented that affects the frame size and that creates a vector of attributes. The policy can be a single decision in response to a random event observed on the frame, or a sequence of such decisions. The goal is to choose policies on each frame in order to maximize a time average of one attribute, subject to additional time average constraints on the others. Two algorithms are developed, both based on Lyapunov optimization concepts. The first makes decisions to minimize a 'drift-plus-penalty' ratio over each frame. The second is similar but does not involve a ratio. For systems that make only a single decision on each frame, both algorithms are shown to learn efficient behavior without a-priori statistical knowledge. The framework is also applicable to large classes of constrained Markov decision problems. Such problems are reduced to finding an approximate solution to a simpler unconstrained stochastic shortest path problem on each frame. Approximations for the simpler problem may still suffer from a curse of dimensionality for systems with large state space. However, our results are compatible with any approximation method, and demonstrate an explicit tradeoff between performance and convergence time. © 2012 IEEE.


Neely M.J.,University of Southern California
IEEE/ACM Transactions on Networking | Year: 2013

It is well known that max-weight policies based on a queue backlog index can be used to stabilize stochastic networks, and that similar stability results hold if a delay index is used. Using Lyapunov optimization, we extend this analysis to design a utility maximizing algorithm that uses explicit delay information from the head-of-line packet at each user. The resulting policy is shown to ensure deterministic worst-case delay guarantees and to yield a throughput utility that differs from the optimally fair value by an amount that is inversely proportional to the delay guarantee. Our results hold for a general class of 1-hop networks, including packet switches and multiuser wireless systems with time-varying reliability. © 1993-2012 IEEE.


Link P.E.,University of California at Los Angeles | Palinkas L.A.,University of Southern California
Clinical Child and Family Psychology Review | Year: 2013

The deployment of US military personnel to recent conflicts has been a significant stressor for their families; yet, we know relatively little about the long-term family effects of these deployments. Using data from prior military service eras, we review our current understanding of the long-term functioning and needs of military families. These data suggest that overseas deployment, exposure to combat, experiencing or participating in violence during war deployment, service member injury or disability, and combat-related post-traumatic stress disorder (PTSD) all have profound impacts on the functioning of military families. We offer several recommendations to address these impacts such as the provision of family-centered, trauma-informed resources to families of veterans with PTSD and veterans who experienced high levels of combat and war violence. Recent efforts to address the needs of caregivers of veterans should be evaluated and expanded, as necessary. We should also help military families plan for predictable life events likely to challenge their resilience and coping capacities. Future research should focus on the following: factors that mediate the relationship between PTSD, war atrocities, caregiver burden, and family dysfunction; effective family-centered interventions that can be scaled-up to meet the needs of a dispersed population; and system-level innovations necessary to ensure adequate access to these interventions. © 2013 Springer Science+Business Media New York.


Weitz I.C.,University of Southern California
Seminars in Thrombosis and Hemostasis | Year: 2011

Paroxysmal nocturnal hemoglobinuria is a disorder associated with hemolysis, pancytopenia, and thrombosis due to the loss of the glycosylphosphatidylinositol (GPI) anchored complement regulatory proteins. The mechanism of thrombosis is multifactorial. Although intravascular hemolysis has been implicated as the etiology, the effect of complement on GPI anchor-deficient platelets, granulocytes, monocytes, and endothelial cells contributes significantly to the risk of thrombosis. Moreover, there appears to be an underlying inflammatory state that is linked to hemostatic activation that may induce thrombosis through a pathway independent of hemolysis. Copyright © 2011 by Thieme Medical Publishers, Inc.


Ginat D.T.,Harvard University | Schatz C.J.,University of Southern California
American Journal of Neuroradiology | Year: 2013

SUMMARY: Injectable fillers are increasingly used for midface augmentation, which can be performed for facial rejuvenation and treatment of HIV facial lipoatrophy. A variety of temporary and permanent filler agents has been developed, including calcium hydroxylapatite, collagen, liquid silicone, polytetrafluoroethylene, hyaluronic acid, poly-L-lactic acid, and polyacrylamide gel. Facial fillers are sometimes encountered on radiologic imaging incidentally and should not be mistaken for pathology. Alternatively, patients with facial fillers may undergo imaging specifically to evaluate associated complications, such as infection, overfilling, migration, foreign-body reaction, and scarring. Therefore, it is important to be familiar with the imaging appearances of the various filler materials and their complications.


Pandya A.,University of Southern California
Canadian Journal of Psychiatry | Year: 2013

Objective: Various mental health services were provided in New York City in the response to the September 11 attacks. This article describes these services and the subsequent research in disaster psychiatry to identify recommended practices for future disasters. Method: A PubMed search identified 198 articles since the 9/11 attacks that included "New York City," and either "9/11" or "disaster," and either "psychiatry" or "mental health." The abstracts of all of these articles were reviewed to identify articles that described clinical services and those articles were then reviewed in detail. Additional reports on 9/11-related services were identified through book chapters. Results: Acute services included debriefings and other single-time outreach interventions. Postacute phase interventions included community outreach with the goal of addressing normative psychological sequelae, multisession interventions based on evidence-based treatments, and hospital-based psychiatric services provided in the context of general health screenings for response workers. Conclusions: Many programs integrated medical and nonmedical services. The professional literature in the decade since this disaster has shifted recommended practices away from psychological debriefings in the acute phase to the implementation of psychological first aid (PFA). Many of the acute 9/11-related services actually closely resembled PFA. In the postacute phase, resources need to be made available for more resource-intensive psychiatric treatment for the fraction of survivors who develop psychiatric illness.


Baydur A.,University of Southern California
Current Opinion in Pulmonary Medicine | Year: 2012

PURPOSE OF REVIEW: This review emphasizes key findings in physiologic research of sarcoidosis reported over the past year. RECENT FINDINGS: Sarcoidosis, a multiorgan disease involving the formation of epithelioid-cell granulomas, is characterized by reduced lung volumes, compliance, and diffusion capacity (DLCO), and, in a small number of cases, by airflow limitation. Recent studies do not show a close relationship between changes in lung volume and radiographic stage. Fatigue and exercise limitation are characteristic of this condition, and can be assessed by health-related quality of life (HRQOL) instruments. Recent investigations have focused on the evaluation of the extent of parenchymal and nodal inflammatory activity by PET using 18F- fluorodeoxyglucose (FDG-PET imaging). Pulmonary hypertension in advanced cases of sarcoidosis contributes to increased physical impairment, and decreased HRQOL and survival. It is best associated with ambulatory desaturation, reduced DLCO, and abnormal cardiopulmonary exercise testing findings indicative of pulmonary vascular disease. If pulmonary hypertension is suspected, it should be screened for by echocardiography and confirmed by right heart catheterization. Selected patients with progressive disease unresponsive to medical therapy or with severe pulmonary hypertension should be considered for lung transplantation. Current criteria for lung transplantation include New York Heart Association functional class III-IV, pulmonary hypertension, and/or right atrial pressure at least 15mmHg. SUMMARY: Periodic assessment of HRQOL measures, exercise-induced hypoxemia, and right-sided cardiac pressures for pulmonary hypertension provides, to date, the best insight into the magnitude of physiologic impairment, serving as guideposts for management (including lung transplantation) and prognosis. Copyright © 2012 Lippincott Williams & Wilkins.


Johnson K.A.,University of Southern California
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Economic evaluation in health care is increasingly used to assist policy makers in their difficult task of allocating limited resources. The high cost of care, including that for clotting factor concentrates, makes hemophilia a potential target for cost-cutting efforts by health care payers. Although the appropriate management of hemophilia is key to minimizing and preventing long-term morbidity, comparative effectiveness studies regarding the relative benefit of different treatment options are lacking. Cost-of-illness (COI) analysis, which includes direct and indirect costs from a societal perspective, can provide information to be used in cost-effectiveness and other economic analyses. Quality-of-life assessment provides another methodology with which to measure outcomes and benefits of appropriate disease management. Health care reform has implications for individuals with hemophilia and their families through changes in payment, insurance coverage expansion, and health care delivery system changes that reward quality and stimulate cooperative, team-based care. Providers will benefit from the expansion of insurance coverage and some financial benefits in rural areas, and from the expansion of coverage for preventive services. Accountable care organizations will potentially change the way providers are paid and financial incentives under reform will reward high quality of care.


Sokol R.Z.,University of Southern California
Fertility and Sterility | Year: 2012

Important medical conditions associated with Klinefelter syndrome (KS) are categorized as: 1) motor, cognitive, and behavioral dysfunction; 2) tumors; 3) vascular disease; and 4) endocrine/metabolic and autoimmune diseases. Earlier diagnosis of KS may lead to earlier intervention with effective treatment. Copyright © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.


Medeiros D.M.,University of Colorado at Boulder | Crump J.G.,University of Southern California
Developmental Biology | Year: 2012

Patterning of the vertebrate facial skeleton involves the progressive partitioning of neural-crest-derived skeletal precursors into distinct subpopulations along the anteroposterior (AP) and dorsoventral (DV) axes. Recent evidence suggests that complex interactions between multiple signaling pathways, in particular Endothelin-1 (Edn1), Bone Morphogenetic Protein (BMP), and Jagged-Notch, are needed to pattern skeletal precursors along the DV axis. Rather than directly determining the morphology of individual skeletal elements, these signals appear to act through several families of transcription factors, including Dlx, Msx, and Hand, to establish dynamic zones of skeletal differentiation. Provocatively, this patterning mechanism is largely conserved from mouse and zebrafish to the jawless vertebrate, lamprey. This implies that the diversification of the vertebrate facial skeleton, including the evolution of the jaw, was driven largely by modifications downstream of a conversed pharyngeal DV patterning program. © 2012 Elsevier Inc.


Wein A.,U.S. Geological Survey | Rose A.,University of Southern California
Earthquake Spectra | Year: 2011

Following a damaging earthquake, "business interruption" (BI)-reduced production of goods and services-begins and continues long after the ground shaking stops. Economic resilience reduces BI losses by making the best use of the resources available at a given point in time (static resilience) or by speeding recovery through repair and reconstruction (dynamic resilience), in contrast to mitigation that prevents damage in the first place. Economic resilience is an important concept to incorporate into economic loss modeling and in recovery and contingency planning. Economic resilience framework includes the applicability of resilience strategies to production inputs and output, demand- and supplyside effects, inherent and adaptive abilities, and levels of the economy. We use our resilience framework to organize and share strategies that enhance economic resilience, identify overlooked resilience strategies, and present evidence and structure of resilience strategies for economic loss modelers. Numerous resilience strategies are compiled from stakeholder discussions about the ShakeOut Scenario (Jones et al. 2008). Modeled results of ShakeOut BI sector losses reveal variable effectiveness of resilience strategies for lengthy disruptions caused by fire-damaged buildings and water service outages. Resilience is a complement to mitigation and may, infact, have cost and all-hazards advantages. © 2011 Earthquake Engineering Research Institute.


Unger J.B.,University of Southern California
Child Development Perspectives | Year: 2014

Hispanic adolescents represent a growing segment of the U.S. population. In addition to the typical stressors encountered during adolescence, Hispanic adolescents may experience acculturative stress, perceived discrimination, and conflicts with parents about acculturation, which can lead to maladaptive behaviors such as substance use. Personal cultural resources may help Hispanic youth cope with cultural stressors and avoid substance use, but little is known about how such factors affect decisions about substance use. In 2005, my research group began studying a group of Hispanic adolescents in Los Angeles. The participants completed surveys annually about cultural issues such as acculturation, ethnic identity, and perceived discrimination; family and peer relationships; and use of alcohol, tobacco, and marijuana. We found that Hispanic adolescents' perceptions that they were discriminated against put them at greater risk for substance use, and that Hispanic orientation protected the youth from substance use. The findings can inform the development of culturally relevant prevention interventions for Hispanic adolescents and emerging adults. © 2014 The Author. Child Development Perspectives © 2014 The Society for Research in Child Development.


Raza H.,University of Southern California
IEEE Communications Magazine | Year: 2013

In part I of this article we presented the design alternatives, issues, and challenges for designing backhaul for 2G (GSM, CDMA) and 3G (UMTS, CDMA2000) radio access networks (RANs). Part II extends the survey of backhaul technologies to address LTE-based RANs. We present various alternatives to deal with the specific requirements imposed by Evolved Packet System architecture on the backhaul design. In particular, we address handling of the X2 interface, network security through IPSec, distribution of frequency and phase synchronization, the impact of small cell design, self-organizing networks, and endend QoS management within backhaul. We also present a brief overview of active debates with respect to some of these design options as open issues, in particular the impact of LTE-Advanced requirements on LTE backhaul design. © 2013 IEEE.


Shammas H.J.,University of Southern California
Journal of Cataract and Refractive Surgery | Year: 2010

Purpose: To evaluate the precision of the axial length (AL), keratometry (K), anterior chamber depth (ACD), astigmatism, and minus astigmatic cylinder axis measurements by a partial coherence interferometry (PCI)-keratometry device. Setting: Private practice, Lynwood, California. Methods: This prospective comparative observational study analyzed measurements in the second eye to have cataract surgery. Before surgery in the first eye, AL, K, ACD, astigmatism, and cylinder axis in both eyes were measured with an IOLMaster PCI device. The measurements were repeated approximately 1 month later, before second eye-surgery. The 2 sets of measurements were compared. Results: The study evaluated 121 eyes of 121 patients. The interclass correlation coefficient (ICC) for AL was 0.999 in all 3 signal-to-noise ratio (SNR) categories; the highest difference range was with an SNR below 100. Astigmatism, K, and cylinder axis had a high correlation in flat corneas (K reading <42.0 diopters [D]) (ICC = 0.994, 0.978, and 0.918, respectively) and a poorer correlation with K readings between 42.0 D and 44.0 D (ICC = 0.905, 0.774, and 0.456, respectively) and K readings above 44.0 D (ICC = 0.988, 0.729 and 0.446, respectively). Conclusions: The precision of the PCI measurements was extremely high for AL with low fluctuations (95% limits of agreement [LoA], 0.06 mm) and was relatively high for K readings with higher fluctuations (95% LoA, 0.55 D) and for ACD (95% LoA, 0.2 mm). The precision of astigmatism and cylinder axis was high in flat corneas and relatively low in steeper corneas. Financial Disclosure: Neither author has a financial or proprietary interest in any material or method mentioned. © 2010 ASCRS and ESCRS.


A series of experiments have been carried out on gravity currents released from locks of various dimensions into a sloping, open channel. Initially all the driving heads of the gravity currents grew by addition of heavier material from a following down-slope flow and by entrainment of ambient fluid, as in Maxworthy & Nokes (J. Fluid Mech., vol. 584, 2007, pp. 433-453). After propagating a distance of the order of 5-10 lock lengths the inflow into the rear stopped, and the head began to lose buoyancy-containing fluid from its rear by the detachment of large, weakly vortical structures. At the same time it was still entraining fluid over the majority of its surface so that its mean density was reduced. Measurements using a semi-direct method, in which dye concentration was used as a surrogate for density, have shown that the buoyancy in the current head increased during the first phase and decreased during the second. At no stage was the buoyancy constant except, of course, at the location and time at which the buoyancy was maximum with a magnitude significantly smaller than the initial value in the lock. Despite this the constant buoyancy theory of Beghin, Hopfinger & Britter (J. Fluid Mech., vol. 107, 1981, pp. 407-422), in which the head location x varies with time t as t2/3 during the later velocity-decay stage of the evolution, was found to be remarkably robust as a description of the evolution over both the latter part of the increasing-buoyancy stage and all of the decreasing-buoyancy phase. Critically, however, the multiplying coefficient had to be smaller than presented by them in order to track the experimental data with precision. This was due principally to the observation that the buoyancy at the beginning of the decay phase was considerably smaller than the initial buoyancy in the lock. © 2010 Cambridge University Press.


Edwards K.J.,University of Southern California | Becker K.,University of Miami | Colwell F.,Oregon State University
Annual Review of Earth and Planetary Sciences | Year: 2012

Most ecosystems on Earth exist in permanent darkness, one or more steps removed from the light-driven surface world. This collection of dark habitats is the most poorly understood on Earth, in particular the size, function, and activity of these ecosystems and what influence they have on global biogeochemical processes. The vastest of these ecosystems constitute the "deep biosphere"-habitats physically located below the surface of continents and the bottom of the ocean. The deep biosphere has been the subject of considerable-and increasing-study and scrutiny in recent years. New deep biosphere realms are being explored from deep in mines in South Africa, to sediments in the middle of oceanic gyres-and beyond. New technologies are emerging, permitting researchers to do active, manipulable experimentation in situ within the subsurface. This review highlights recent history of the research and the exciting new directions this field of research is going in, and discusses some of the most active and interesting field realms currently under scrutiny by researchers examining this deep, dark, intraterrestrial life. © 2012 by Annual Reviews. All rights reserved.


Lie D.A.,University of Southern California
Medical education online | Year: 2013

The validated 19-item Readiness for Interprofessional Learning Scale (RIPLS) is often used for assessing attitudes toward interprofessional education (IPE). The 12-item Interdisciplinary Education Perception Scale (IEPS), also used for this purpose, has not been validated among the professions of medicine, pharmacy, and physician assistants (PAs). The discriminatory ability of the two scales has not been directly compared. Comparison of the two will aid educators in selecting the optimal scale. To compare psychometric properties of the RIPLS and IEPS and to examine the ability of each scale to discriminate mean scores among student subgroups (gender, profession, seniority, and prior IPE exposure). We conducted a cross-sectional (Qualtrics(©)) survey (RIPLS and IEPS) of junior and senior students in medicine (n=360), pharmacy (n=360), and the PA profession (n=106). Descriptive statistics were used to report aggregate mean scores of subgroups. The internal consistency of each scale was assessed using Cronbach's α. Concurrent validity was measured by Pearson's correlation coefficients. Independent-sample t-tests and analysis of variances (ANOVAs) were performed to assess the discriminatory ability of each scale. Cohen's d effect sizes were calculated for all significant pair-wise comparisons. Response rate was 82%. Cronbach's α was 0.85 (RIPLS) and 0.91 (IEPS). The RIPLS discriminated scores by gender among junior students only, and scores by IPE exposure among all students. The IEPS distinguished score differences for the three professions among junior students and by prior IPE exposure for all three professions. Neither scale detected differences in mean scores by profession among all students or by level of training among the three professions. Neither the RIPLS nor the IEPS has greater discriminatory ability for detecting attitude differences among the student subgroups. Reason for differences may be explained by slightly different scale constructs. The RIPLS is designed to assess students' own attitude toward interprofessional learning, while the IEPS discerns perceived attitudes about team collaboration for students' own professions and may be more appropriate for more advanced students.


Duffy D.M.,University of Southern California
Dermatologic Surgery | Year: 2010

BACKGROUND Sclerotherapy is popular for the treatment of lower extremity telangiectasias and varicose and reticular veins. Although a large number of sclerosants are commonly employed, there are few data that directly compare their advantages and drawbacks. OBJECTIVES To analyze and present the differences between sclerosants that make them more or less suitable agents in specific clinical applications. MATERIALS AND METHODS A systemic review of published medical literature that compares and contrasts different classes of sclerosants is presented. RESULTS There is no perfect sclerosant that is complication free and 100% effective. The ability to match the sclerosant to the clinical problem being approached makes the availability of more Food and Drug Administration-approved sclerosants appealing. CONCLUSION Modern sclerosants that have been subjected to rigorous experimental and clinical trials will provide even more efficacious and safer patient treatments. David M. Duffy, MD, received a grant from Bioform for support of this article. © 2010 by the American Society for Dermatologic Surgery, Inc.


McDonough A.A.,University of Southern California
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2010

One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na+ and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na+/H+ exchanger isoform 3 (NHE3) and the Na +-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na + transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS. Copyright © 2010 the American Physiological Society.


Griffin J.H.,Scripps Research Institute | Zlokovic B.V.,University of California at San Diego | Mosnier L.O.,University of Southern California
Blood | Year: 2015

The homeostatic blood protease, activated protein C (APC), can function as (1) an antithrombotic on the basis of inactivation of clotting factors Va and VIIIa; (2) a cytoprotective on the basis of endothelial barrier stabilization and anti-inflammatory and antiapoptotic actions; and (3) a regenerative on the basis of stimulation of neurogenesis, angiogenesis, and wound healing. Pharmacologic therapies using recombinant human and murine APCs indicate that APC provides effective acute or chronic therapies for a strikingly diverse range of preclinical injury models. APC reduces the damage caused by the following: ischemia/reperfusion in brain, heart, and kidney; pulmonary, kidney, and gastrointestinal inflammation; sepsis; Ebola virus; diabetes; and total lethal body radiation. For these beneficial effects, APC alters cell signaling networks and gene expression profiles by activating protease-activated receptors 1 and 3. APC's activation of these G protein-coupled receptors differs completely from thrombin's activation mechanism due to biased signaling via either G proteins or β-arrestin-2. To reduce APC-associated bleeding risk, APC variants were engineered to lack >90% anticoagulant activity but retain normal cell signaling. Such a neuroprotective variant, 3K3A-APC (Lys191-193Ala), has advanced to clinical trials for ischemic stroke. A rich data set of preclinical knowledge provides a solid foundation for potential translation of APC variants to future novel therapies. © 2015 by The American Society of Hematology.


Yap L.P.,University of Southern California
Methods in enzymology | Year: 2010

GSNO is an important intermediate in nitric oxide metabolism and mediates many ()NO-mediated signaling pathways through the post-translational modification of redox-sensitive proteins. The detection of GSNO in biological samples has been hampered by a lack of sensitive and simple assays. In this work, we describe the utilization of HPLC with electrochemical detection for the identification and quantification of GSNO in biological samples. GSNO requires a high potential (>700 mV) for its electrochemical detection, similar to that of GSSG. A simple isocratic HPLC system can be used to separate and simultaneously detect GSH, GSSG, and GSNO electrochemically. This HPLC system can be utilized to measure the redox profile of biological samples and applied for the measurement of GSNO reductase activity in cells. Proper sample preparation is essential in GSNO measurements, because artifactual formation of GSNO occurs in acidic conditions due to the reaction between GSH and nitrite. Treatment of samples with ammonium sulfamate or N-ethylmaleimide (NEM) can prevent the artifactual formation of GSNO and accurately detect GSNO in biological samples. Overall, the HPLC with electrochemical detection is a powerful tool to measure redox status in cells and tissues. Copyright (c) 2010 Elsevier Inc. All rights reserved.


Lieber M.R.,University of Southern California
Annual Review of Biochemistry | Year: 2010

Double-strand DNA breaks are common events in eukaryotic cells, and there are two major pathways for repairing them: homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). The various causes of double-strand breaks (DSBs) result in a diverse chemistry of DNA ends that must be repaired. Across NHEJ evolution, the enzymes of the NHEJ pathway exhibit a remarkable degree of structural tolerance in the range of DNA end substrate configurations upon which they can act. In vertebrate cells, the nuclease, DNA polymerases, and ligase of NHEJ are the most mechanistically flexible and multifunctional enzymes in each of their classes. Unlike repair pathways for more defined lesions, NHEJ repair enzymes act iteratively, act in any order, and can function independently of one another at each of the two DNA ends being joined. NHEJ is critical not only for the repair of pathologic DSBs as in chromosomal translocations, but also for the repair of physiologic DSBs created during variable (diversity) joining [V(D)J] recombination and class switch recombination (CSR). Therefore, patients lacking normal NHEJ are not only sensitive to ionizing radiation (IR), but also severely immunodeficient. © 2010 by Annual Reviews. All rights reserved.


Mi H.,University of Southern California
Nature protocols | Year: 2013

The PANTHER (protein annotation through evolutionary relationship) classification system (http://www.pantherdb.org/) is a comprehensive system that combines gene function, ontology, pathways and statistical analysis tools that enable biologists to analyze large-scale, genome-wide data from sequencing, proteomics or gene expression experiments. The system is built with 82 complete genomes organized into gene families and subfamilies, and their evolutionary relationships are captured in phylogenetic trees, multiple sequence alignments and statistical models (hidden Markov models or HMMs). Genes are classified according to their function in several different ways: families and subfamilies are annotated with ontology terms (Gene Ontology (GO) and PANTHER protein class), and sequences are assigned to PANTHER pathways. The PANTHER website includes a suite of tools that enable users to browse and query gene functions, and to analyze large-scale experimental data with a number of statistical tests. It is widely used by bench scientists, bioinformaticians, computer scientists and systems biologists. In the 2013 release of PANTHER (v.8.0), in addition to an update of the data content, we redesigned the website interface to improve both user experience and the system's analytical capability. This protocol provides a detailed description of how to analyze genome-wide experimental data with the PANTHER classification system.


Jena A.B.,Harvard University | Seabury S.,RAND | Lakdawalla D.,University of Southern California | Chandra A.,Harvard University
New England Journal of Medicine | Year: 2011

BACKGROUND: Data are lacking on the proportion of physicians who face malpractice claims in a year, the size of those claims, and the cumulative career malpractice risk according to specialty. METHODS: We analyzed malpractice data from 1991 through 2005 for all physicians who were covered by a large professional liability insurer with a nationwide client base (40,916 physicians and 233,738 physician-years of coverage). For 25 specialties, we reported the proportion of physicians who had malpractice claims in a year, the proportion of claims leading to an indemnity payment (compensation paid to a plaintiff), and the size of indemnity payments. We estimated the cumulative risk of ever being sued among physicians in high- and low-risk specialties. RESULTS: Each year during the study period, 7.4% of all physicians had a malpractice claim, with 1.6% having a claim leading to a payment (i.e., 78% of all claims did not result in payments to claimants). The proportion of physicians facing a claim each year ranged from 19.1% in neurosurgery, 18.9% in thoracic-cardiovascular surgery, and 15.3% in general surgery to 5.2% in family medicine, 3.1% in pediatrics, and 2.6% in psychiatry. The mean indemnity payment was $274,887, and the median was $111,749. Mean payments ranged from $117,832 for dermatology to $520,923 for pediatrics. It was estimated that by the age of 65 years, 75% of physicians in lowrisk specialties had faced a malpractice claim, as compared with 99% of physicians in high-risk specialties. CONCLUSIONS: There is substantial variation in the likelihood of malpractice suits and the size of indemnity payments across specialties. The cumulative risk of facing a malpractice claim is high in all specialties, although most claims do not lead to payments to plaintiffs. (Funded by the RAND Institute for Civil Justice and the National Institute on Aging.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Fujimoto K.,University of Houston | Valente T.W.,University of Southern California
Journal of Adolescent Health | Year: 2012

Purpose: Friendship networks are an important source of peer influence. However, existing network studies vary in terms of how they operationalize friendship and friend's influence on adolescent substance use. This study uses social network analysis to characterize three types of friendship relations: (1) mutual or reciprocated, (2) directional, and (3) intimate friends. We then examine the relative effects of each friendship type on adolescent drinking and smoking behavior. Methods: Using a saturated sample from the Add Health data, a nationally representative sample of high school adolescents (N = 2,533 nested in 12 schools), we computed the level of exposure to drinking and smoking of friends using a network exposure model, and their association with individual drinking and smoking using fixed effect models. Results: Results indicated that the influence from mutual or reciprocated type of friendship relations is stronger on adolescent substance use than directional, especially for smoking. Regarding the directionality of directional type of friendship relations, adolescents are equally influenced by both nominating and nominated friends on their drinking and smoking behavior. Results for intimate friends friendship relations indicated that the influence from "best friends" was weaker than the one from non - "best friends," which indicates that the order of friend nomination may not matter as much as nomination reciprocation. Conclusions: This study demonstrates that considering different features of friendship relationships is important in evaluating friends' influence on adolescent substance use. Related policy implications are discussed. © 2012 Society for Adolescent Health and Medicine. All rights reserved.


Solomon O.,University of Southern California
Culture, Medicine and Psychiatry | Year: 2015

‘Being autistic’ or ‘having Autism Spectrum Disorder’ implies a limited range of ‘being social,’ but the in situ organization of interaction, what Maynard and Marlaire (Qual Soc 15(2):177–202, 1992) call the ‘interactional substrate,’ within which this delimitation enfolds is usually hidden from sight. Analysis of processes constituting different ‘interactional substrates’ provides a view of how one comes to be known by and to self and others as a certain kind of being who is available (or not) for acting and feeling in certain ways. People diagnosed with Autism Spectrum Disorder (American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013) are often described as ‘being’ impaired in intersubjective understanding of others. But the story of ASD as an impairment of sociality and intersubjectivity becomes more complicated when animals enter into the picture. I consider two interactional substrates: a psychological interview in a mental health clinic, and an animal-assisted activity in a child’s neighborhood. I aim to elucidate the practical problems of ‘being social’ encountered by two children with ASD, both nine-year-old girls, within these two very differently organized interactional substrates. I consider ways in which ‘being with’ therapy animals provides a way of ‘being social’ through “sensory modalities of knowing” (Haraway, When species meet, 2008:371). © 2015, Springer Science+Business Media New York.


McKemy D.D.,University of Southern California
ACS Chemical Neuroscience | Year: 2013

Of somatosensory modalities, cold is one of the more ambiguous percepts, evoking the pleasant sensation of cooling, the stinging bite of cold pain, and welcome relief from chronic pain. Moreover, unlike the precipitous thermal thresholds for heat activation of thermosensitive afferent neurons, thresholds for cold fibers are across a range of cool to cold temperatures that spans over 30 C. Until recently, how cold produces this myriad of biological effects has been poorly studied, yet new advances in our understanding of cold mechanisms may portend a better understanding of sensory perception as well as provide novel therapeutic approaches. Chief among these was the identification of a number of ion channels that either serve as the initial detectors of cold as a stimulus in the peripheral nervous system, or are part of rather sophisticated differential expression patterns of channels that conduct electrical signals, thereby endowing select neurons with properties that are amenable to electrical signaling in the cold. This review highlights the current understanding of the channels involved in cold transduction as well as presents a hypothetical model to account for the broad range of cold thermal thresholds and distinct functions of cold fibers in perception, pain, and analgesia. © 2012 American Chemical Society.


Hofer U.,University of Southern California
The Journal of infectious diseases | Year: 2013

Genetic strategies to block expression of CCR5, the major co-receptor of human immunodeficiency virus type 1 (HIV-1), are being developed as anti-HIV therapies. For example, human hematopoietic stem/precursor cells (HSPC) can be modified by the transient expression of CCR5-targeted zinc finger nucleases (ZFNs) to generate CCR5-negative cells, which could then give rise to HIV-resistant mature CD4(+) T cells following transplantation into patients. The safety and anti-HIV effects of such treatments can be evaluated by transplanting ZFN-treated HSPC into immunodeficient mice, where the extent of human cell engraftment, lineage differentiation and anti-HIV activity arising from the engineered HSPC can be examined. In this way, humanized mice are providing a powerful small animal model for pre-clinical studies of novel anti-HIV therapies.


Mehta V.A.,University of Southern California
Neurosurgery | Year: 2012

The relation of the pelvis to the spine has previously been overlooked as a contributor to sagittal balance. However, it is now recognized that spinopelvic alignment is important to maintain an energy-efficient posture in normal and disease states. The pelvis is characterized by an important anatomic landmark, the pelvic incidence (PI). The PI does not change after adolescence, and it directly influences pelvic alignment, including the parameters of pelvic tilt (PT) and sacral slope (SS) (PI = PT + SS), [corrected] overall sagittal spinal balance, and lumbar lordosis. In the setting of an elevated PI, the spineadapts with increased lumbar lordosis. To prevent or limit sagittal imbalance, the spine may also compensate with increased PT or pelvic retroversion to attempt to maintain anupright posture. Abnormal spinopelvic parameters contribute to multiple spinal conditions including isthmic spondylolysis, degenerative spondylolisthesis, deformity, and impact outcome after spinal fusion. Sagittal balance, pelvic incidence, and all spinopelvic parameters are easily and reliably measured on standing, full-spine (lateral) radiographs, and it is essential to accurately assess and measure these sagittal values to understand their potential role in the disease process, and to promote spinopelvic balance at surgery. In this article, we provide a comprehensive review of the literature regarding the implications of abnormal spinopelvic parameters and discuss surgical strategies for correction of sagittal balance. Additionally, the authors rate and critique the quality of the literature cited in a systematic review approach to give the reader an estimate of the veracity of the conclusions reached from these reports.


Guerrero E.G.,University of Southern California
Journal of Substance Abuse Treatment | Year: 2010

The field of cultural competence is shifting its primary emphasis from enhancement of counselors' skills to management, organizational policy, and processes of care. This study examined managers' characteristics associated with adoption of culturally competent practices in the nation's outpatient substance abuse treatment field. Findings indicate that in 1995, supervisors' cultural sensitivity played the most significant role in adopting practices, such as matching counselors and clients based on race and offering bilingual services. Staff's exposure to cross-cultural training increased from 1995 to 2005. In this period, positive associations were found between managers' cultural sensitivity and connection with the community and staff receiving cross-cultural training and the number of training hours completed. However, exposure to and investment in this training were negatively correlated with managers' formal education. Health administration policy should consider the extent to which the decision makers' education, community involvement, and cultural sensitivity contribute to building culturally responsive systems of care. © 2010 Elsevier Inc.


Zada G.,University of Southern California
Neurosurgical Focus | Year: 2011

The aim of this paper is to provide a comprehensive review of clinical, imaging, and histopathological features, as well as operative and nonoperative management strategies in patients with Rathke cleft cysts (RCCs). A literature review was performed to identify previous articles that reported surgical and nonsurgical management of RCCs. Rathke cleft cysts are often incidental lesions found in the sellar and suprasellar regions and do not require surgical intervention in the majority of cases. In symptomatic RCCs, the typical clinical presentation includes headache, visual loss, and/or endocrine dysfunction. Visual field testing and endocrine laboratory studies may reveal more subtle deficiencies associated with RCCs. When indicated, the transsphenoidal approach typically offers the least invasive and safest method for treating these lesions. Various surgical strategies including cyst wall resection, intralesional alcohol injection, and sellar floor reconstruction are discussed. Although headache and visual symptoms frequently improve after surgical drainage of RCCs, hypopituitarism and diabetes insipidus are less likely to do so. A subset of more aggressive, atypical RCCs associated with pronounced clinical symptoms and higher recurrence rates is discussed, as well as the possible relationship of these lesions to craniopharyngiomas. Rathke cleft cysts are typically benign, asymptomatic lesions that can be monitored. In selected patients, transsphenoidal surgery provides excellent rates of improvement in clinical symptoms and long-term cyst resolution. Complete cyst wall resection, intraoperative alcohol cauterization, and sellar floor reconstruction in the absence of a CSF leak are not routinely recommended.


Jain R.,University of Southern California
IEEE Communications Magazine | Year: 2012

Markets for network resources have become increasingly important. Such resources include bandwidth in wireline networks to wireless spectrum. It is clear that if the markets are not properly designed, they can function rather poorly, even leading to market failure. This then leads to suboptimal use of network resources. In this article, we present the game theoretic framework behind the market design principles for network resources. We present some of the extant work on network market mechanisms in the context of wireline networks in part I. Part II [1] relates to network market design in the context of wireless systems. We also discuss some of the key challenges for the future. © 2012 IEEE.


Urgaonkar R.,Raytheon Co. | Neely M.J.,University of Southern California
IEEE Journal on Selected Areas in Communications | Year: 2012

We investigate optimal routing and scheduling strategies for multi-hop wireless networks with rateless codes. Rateless codes allow each node of the network to accumulate mutual information with every packet transmission. This enables a significant performance gain over conventional shortest path routing. Further, it also outperforms cooperative communication techniques that are based on energy accumulation. However, it creates complex and combinatorial networking decisions concerning which nodes participate in transmission, and which decode ordering to use. We formulate three problems of interest in this setting: (i) minimum delay routing, (ii) minimum energy routing subject to delay constraint, and (iii) minimum delay broadcast. All of these are hard combinatorial optimization problems and we make use of several structural properties of their optimal solutions to simplify the problems and derive optimal greedy algorithms. Although the reduced problems still have exponential complexity, unlike prior works on such problems, our greedy algorithms are simple to use and do not require solving any linear programs. Further, using the insight obtained from the optimal solution to a linear network, we propose two simple heuristics that can be implemented in polynomial time in a distributed fashion and compare them with the optimal solution. Simulations suggest that both heuristics perform very close to the optimal solution over random network topologies. © 2012 IEEE.


Jurow M.J.,University of Southern California
Nature Materials | Year: 2015

Controlling the alignment of the emitting molecules used as dopants in organic light-emitting diodes is an effective strategy to improve the outcoupling efficiency of these devices. To explore the mechanism behind the orientation of dopants in films of organic host materials, we synthesized a coumarin-based ligand that was cyclometalated onto an iridium core to form three phosphorescent heteroleptic molecules, (bppo)2Ir(acac), (bppo)2Ir(ppy) and (ppy)2Ir(bppo) (bppo represents benzopyranopyridinone, ppy represents 2-phenylpyridinate, and acac represents acetylacetonate). Each emitter was doped into a 4,4′-bis(N-carbazolyl)-1,1′-biphenyl host layer, and the resultant orientation of their transition dipole moment vectors was measured by angle-dependent p-polarized photoluminescent emission spectroscopy. In solid films, (bppo)2Ir(acac) is found to have a largely horizontal transition dipole vector orientation relative to the substrate, whereas (ppy)2Ir(bppo) and (bppo)2Ir(ppy) are isotropic. We propose that the inherent asymmetry at the surface of the growing film promotes dopant alignment in these otherwise amorphous films. Modelling the net orientation of the transition dipole moments of these materials yields general design rules for further improving horizontal orientation. © 2015 Nature Publishing Group


Schrenk M.O.,East Carolina University | Huber J.A.,Josephine Bay Paul Center | Edwards K.J.,University of Southern California
Annual Review of Marine Science | Year: 2010

The rocks and sediments of the oceanic subsurface represent a diverse mosaic of environments potentially inhabited by microorganisms. Understanding microbial ecosystems in subseafloor environments confounds standard ecological descriptions in part because we have difficulty elucidating and describing the scale of relevant processes. Habitat characteristics impact microbial activities and growth, which in turn affect microbial diversity, net production, and global biogeochemical cycles. Herein we provide descriptions of subseafloor microbial provinces, broadly defined as geologically and geographically coherent regions of the subseafloor that may serve as potential microbial habitats. The purpose of this review is to summarize and refine criteria for the definition and delineation of distinct subseafloor microbial habitats to aid in their exploration. This review and the criteria we outline aim to develop a unified framework to improve our understanding of subseafloor microbial ecology, enable quantification of geomicrobial processes, and facilitate their accurate assimilation into biogeochemical models. © 2010 by Annual Reviews.


Goldman D.P.,University of Southern California | Philipson T.,University of Chicago
Health Affairs | Year: 2014

In this commentary we debunk a number of the most common misconceptions about cancer treatment, such as claims that the war on cancer has been a failure and that treatment costs are unsustainable. In addition, there is good evidence that patients value these treatments more highly than traditional cost-effectiveness analysis would indicate. We argue that coverage policies placing undue burden on patients are socially wasteful and will likely discourage further innovation. © 2014 Project HOPE-The People-to-People Health Foundation, Inc.


Setiawan V.W.,University of Southern California
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.


Zhang H.F.,University of Southern California
Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye | Year: 2011

Photoacoustic ophthalmoscopy (PAOM) is a new retinal imaging technology that offers the unique capability to measure optical absorption in the retina. Because PAOM is compatible with optical coherence tomography, scanning laser ophthalmoscopy, and autofluorescence imaging, registered multimodal images can be acquired from a single device at comparable resolution for comprehensive anatomic and functional retinal characterizations. Therefore, PAOM is anticipated to have applications in both research and clinical diagnosis of many blinding diseases. The authors explain the basic principles of the photoacoustic effect and imaging. Then, different types of photoacoustic microscopy are introduced and compared. Finally, the current status of photoacoustic imaging in animal eyes is presented and the prospects of future development of PAOM are suggested. Copyright 2011, SLACK Incorporated.


Gruntman M.,University of Southern California
Journal of Geophysical Research A: Space Physics | Year: 2015

The expanding solar wind plasma undergoes a shock transition at the interstellar boundary of the solar system and fills the inner heliosheath, the region between the termination shock and the heliopause. The nonequilibrium heliosheath plasma is a main source of energetic neutral atoms that allow remote probing of the heliospheric interface region. Global models of the heliosphere interaction with the interstellar medium often disregard solar photoionization and electron impact ionization of interstellar gas in the heliosheath. When ionization is included, it is commonly treated in a simplified manner and complexity of heliospheric interactions obscures its effect on the properties of the plasma. This work concentrates on physical estimates of ionization and shows that it may lead to significant mass loading of plasma flows in the heliosheath. In turn, mass loading would slow down plasma flows and deplete populations of nonthermal energetic protons. The magnitude of the effect depends on poorly understood and largely unknown energy transfer to electrons at the termination shock and beyond. The presented estimates show that inclusion of ionization is indispensable for global heliospheric modeling and for interpretation of heliosphere imaging in fluxes of energetic neutral atoms. ©2015. American Geophysical Union. All Rights Reserved.


Slaymaker I.M.,University of Southern California
Sub-cellular biochemistry | Year: 2012

Minichromosome maintenance (MCM) complexes have been identified as the primary replicative helicases responsible for unwinding DNA for genome replication. The focus of this chapter is to discuss the current structural and functional understanding of MCMs and their role at origins of replication, which are based mostly on the studies of MCM proteins and MCM complexes from archaeal genomes.


Sadhal S.S.,University of Southern California
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

In Part 15 of the tutorial series " Acoustofluidics - exploiting ultrasonic standing waves forces and acoustic streaming in microfluidic systems for cell and particle manipulation," we examine the interaction of acoustic fields with solid particles. The main focus here is the interaction of standing waves with spherical particles leading to streaming, together with some discussion on one non-spherical case. We begin with the classical problem of a particle at the velocity antinode of a standing wave, and then treat the problem of a sphere at the velocity node, followed by the intermediate situation of a particle between nodes. Finally, we discuss the effect of deviation from sphericity which brings about interesting fluid mechanics. The entire Focus article is devoted to the analysis of the nonlinear fluid mechanics by singular perturbation methods, and the study of the streaming phenomenon that ensues from the nonlinear interaction. With the intention of being instructive material, this tutorial cannot by any means be considered 'complete and comprehensive' owing to the complexity of the class of problems being covered herein. © The Royal Society of Chemistry 2012.


McKemy D.D.,University of Southern California
EMBO Journal | Year: 2011

In the current issue, Mishra and colleagues demonstrate that mice lacking somatosensory neurons in the TRPV1 lineage are completely insensitive to thermal stimuli of any quality or modality, including both hot and cold temperatures. TRPV1 is a heat-gated ion channel expressed in most heat-sensitive nociceptive neurons and is the receptor for capsaicin, the pungent ingredient in 'hot' chili peppers (Caterina et al, 1997). In the adult mouse, TRPV1 neurons are molecularly heterogeneous, but channel expression is absent in the majority of coldsensitive neurons labelled with the menthol receptor TRPM8 and all presumptive mechanosensory neurons expressing the Mas-related G protein-coupled receptor D (Mrgprd). However, using a molecular genetic approach to label TRPV1 neurons from the inception of channel expression, the authors find that TRPV1 is a broad developmental marker for the majority of somatosensory neurons, including those expressing Mrgprd and TRPM8. Moreover, genetically targeted ablation of neurons within the TRPV1 lineage eliminates a broad range of mouse behaviours including thermosensation, thermoregulation, nociception, and pruriception, yet these animals retain normal mechanosensation. These results demonstrate that TRPV1 expression predominates embryonically, but is refined over postnatal development. Moreover, other thermosensitive and nociceptive molecules, such as TRPM8, are derived from the TRPV1 lineage even though they are not entirely co-expressed in adults. These findings expand the role of TRPV1 and show the channel has a patriarchal role as a molecular indicator of thermal and nociceptive afferent circuits. © 2011 European Molecular Biology Organization | All Rights Reserved.


Loeb G.E.,University of Southern California
Biological Cybernetics | Year: 2012

The notion that biological systems come to embody optimal solutions seems consistent with the competitive drive of evolution. It has been used to interpret many examples of sensorimotor behavior. It is attractive from the viewpoint of control engineers because it solves the redundancy problem by identifying the one optimal motor strategy out of many similarly acceptable possibilities. This perspective examines whether there is sufficient basis to apply the formal engineering tools of optimal control to a reductionist understanding of biological systems. For an experimental biologist, this translates into whether the theory of optimal control generates nontrivial and testable hypotheses that accurately predict novel phenomena, ideally at deeper levels of structure than the observable behavior. The methodology of optimal control is applicable when there is (i) a single, known cost function to be optimized, (ii) an invertible model of the plant, and (iii) simple noise interfering with optimal performance. None of these is likely to be true for biological organisms. Furthermore, their motivation is usually good-enough rather than globally optimal behavior. Even then, the performance of a biological organism is often much farther from optimal than the physical limits of its hardware because the brain is continuously testing the acceptable limits of performance as well as just performing the task. This perspective considers an alternative strategy called “good-enough” control, in which the organism uses trial-and-error learning to acquire a repertoire of sensorimotor behaviors that are known to be useful, but not necessarily optimal. This leads to a diversity of solutions that tends to confer robustness on the individual organism and its evolution. It is also more consistent with the capabilities of higher sensorimotor structures, such as cerebral cortex, which seems to be designed to classify and recall complex sets of information, thereby allowing the organism to learn from experience, rather than to compute new strategies online. Optimal control has been a useful metaphor for understanding some superficial aspects of motor psychophysics. Reductionists who want to understand the underlying neural mechanisms need to move on. © 2012, Springer-Verlag.


Warshel A.,University of Southern California
Angewandte Chemie - International Edition | Year: 2014

A detailed understanding of the action of biological molecules is a pre-requisite for rational advances in health sciences and related fields. Here, the challenge is to move from available structural information to a clear understanding of the underlying function of the system. In light of the complexity of macromolecular complexes, it is essential to use computer simulations to describe how the molecular forces are related to a given function. However, using a full and reliable quantum mechanical representation of large molecular systems has been practically impossible. The solution to this (and related) problems has emerged from the realization that large systems can be spatially divided into a region where the quantum mechanical description is essential (e.g. a region where bonds are being broken), with the remainder of the system being represented on a simpler level by empirical force fields. This idea has been particularly effective in the development of the combined quantum mechanics/molecular mechanics (QM/MM) models. Here, the coupling between the electrostatic effects of the quantum and classical subsystems has been a key to the advances in describing the functions of enzymes and other biological molecules. The same idea of representing complex systems in different resolutions in both time and length scales has been found to be very useful in modeling the action of complex systems. In such cases, starting with coarse grained (CG) representations that were originally found to be very useful in simulating protein folding, and augmenting them with a focus on electrostatic energies, has led to models that are particularly effective in probing the action of molecular machines. The same multiscale idea is likely to play a major role in modeling of even more complex systems, including cells and collections of cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Hoge C.W.,U.S. Army | Castro C.A.,University of Southern California
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Whether traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD) has been difficult to determine because of the prevalence of comorbid conditions, overlapping symptoms, and cross-sectional samples.OBJECTIVE: To examine the extent to which self-reported predeployment and deployment-related TBI confers increased risk of PTSD when accounting for combat intensity and predeployment mental health symptoms.DESIGN, SETTING, AND PARTICIPANTS: As part of the prospective, longitudinal Marine Resiliency Study (June 2008 to May 2012), structured clinical interviews and self-report assessments were administered approximately 1 month before a 7-month deployment to Iraq or Afghanistan and again 3 to 6 months after deployment. The study was conducted at training areas on a Marine Corps base in southern California or at Veterans Affairs San Diego Medical Center. Participants for the final analytic sample were 1648 active-duty Marine and Navyservicemen who completed predeployment and postdeployment assessments. Reasons for exclusions were nondeployment (n = 34), missing data (n = 181), and rank of noncommissioned and commissioned officers (n = 66).MAIN OUTCOMES AND MEASURES: The primary outcome was the total score on the Clinician-Administered PTSD Scale (CAPS) 3 months after deployment.RESULTS: At the predeployment assessment, 56.8% of the participants reported prior TBI; at postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments (ie, deployment-related TBI). Approximately 87.2% of deployment-related TBIs were mild; 250 of 287 participants (87.1%) who reported posttraumatic amnesia reported less than 24 hours of posttraumatic amnesia (37 reported >24 hours), and 111 of 117 of those who lost consciousness (94.9%) reported less than 30 minutes of unconsciousness. Predeployment CAPS score and combat intensity score raised predicted 3-month postdeployment CAPS scores by factors of 1.02 (P<.001; 95% CI, 1.02-1.02) and 1.02 (P <.001; 95% CI, 1.01-1.02) per unit increase, respectively. Deployment-related mild TBI raised predicted CAPS scores by a factor of 1.23 (P <.001; 95% CI, 1.11-1.36), and moderate/severe TBI raised predicted scores by a factor of 1.71 (P<.001; 95% CI, 1.37-2.12). Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. Traumatic brain injury doubled or nearly doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.CONCLUSIONS AND RELEVANCE: Even when accountingfor predeployment symptoms, prior TBI, and combat intensity, TBI during the most recent deployment is the strongest predictor of postdeployment PTSD symptoms. © 2014 American Medical Association. All rights reserved.


Neely M.J.,University of Southern California
Synthesis Lectures on Communication Networks | Year: 2010

This text presents a modern theory of analysis, control, and optimization for dynamic networks. Mathematical techniques of Lyapunov drift and Lyapunov optimization are developed and shown to enable constrained optimization of time averages in general stochastic systems. The focus is on communication and queueing systems, including wireless networks with time-varying channels, mobility, and randomly arriving traffic. A simple drift-plus-penalty framework is used to optimize time averages such as throughput, throughput-utility, power, and distortion. Explicit performance-delay tradeoffs are provided to illustrate the cost of approaching optimality. This theory is also applicable to problems in operations research and economics, where energy-efficient and profit-maximizing decisions must be made without knowing the future. Topics in the text include the following: • Queue stability theory • Backpressure, max-weight, and virtual queue methods • Primal-dual methods for non-convex stochastic utility maximization • Universal scheduling theory for arbitrary sample paths • Approximate and randomized scheduling theory • Optimization of renewal systems and Markov decision systems Detailed examples and numerous problem set questions are provided to reinforce the main concepts. Copyright © 2010 by Morgan & Claypool.


Tower J.,University of Southern California
Ageing Research Reviews | Year: 2015

Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction. © 2015 Elsevier B.V.


Sarwate A.D.,Toyota USA | Dimakis A.G.,University of Southern California
IEEE Transactions on Information Theory | Year: 2012

The influence of node mobility on the convergence time of averaging gossip algorithms in networks is studied. It is shown that a small number of fully mobile nodes can yield a significant decrease in convergence time. A method is developed for deriving lower bounds on the convergence time by merging nodes according to their mobility pattern. This method is used to show that if the agents have 1-D mobility in the same direction, the convergence time is improved by at most a constant. Upper bounds on the convergence time are obtained using techniques from the theory of Markov chains and show that simple models of mobility can dramatically accelerate gossip as long as the mobility paths overlap significantly. Simulations verify that different mobility patterns can have significantly different effects on the convergence of distributed algorithms. © 2012 IEEE.


Zhang J.,University of Southern California
Genetic epidemiology | Year: 2014

Association analysis using admixed populations imposes challenges and opportunities for disease mapping. By developing some explicit results for the variance of an allele of interest conditional on either local or global ancestry and by simulation of recently admixed genomes we evaluate power and false-positive rates under a variety of scenarios concerning linkage disequilibrium (LD) and the presence of unmeasured variants. Pairwise LD patterns were compared between admixed and nonadmixed populations using the HapMap phase 3 data. Based on the above, we showed that as follows: For causal variants with similar effect size in all populations, power is generally higher in a study using admixed population than using nonadmixed population, especially for highly differentiated SNPs. This gain of power is achieved with adjustment of global ancestry, which completely removes any cross-chromosome inflation of type I error rates, and addresses much of the intrachromosome inflation. If reliably estimated, adjusting for local ancestry precisely recovers the localization that could have been achieved in a stratified analysis of source populations. Improved localization is most evident for highly differentiated SNPs; however, the advantage of higher power is lost on exactly the same differentiated SNPs. In the real admixed populations such as African Americans and Latinos, the expansion of LD is not as dramatic as in our simulation. While adjustment for global ancestry is required prior to announcing a novel association seen in an admixed population, local ancestry adjustment may best be regarded as a localization tool not strictly required for discovery purposes. © 2014 WILEY PERIODICALS, INC.


Hora S.C.,University of Southern California
Operations Research | Year: 2010

It is shown how infinite sequences of densities with defined properties can be used to evaluate the expected performance of mathematical aggregation rules for elicited densities. The performance of these rules is measured through the average variance, calibration, and average Brier score of the aggregates. A general result for the calibration of the arithmetic average of densities from well-calibrated independent experts is given. Arithmetic and geometric aggregation rules are compared using sequences of normal densities. Sequences are developed that exhibit dependence among experts and lack of calibration. The impact of correlation, number of experts, and degree of calibration on the performance of the aggregation is demonstrated.©2010 INFORMS.


Zhang H.,University of Southern California
Operations Research | Year: 2010

This paper presents a novel framework for studying partially observable Markov decision processes (POMDPs) with finite state, action, observation sets, and discounted rewards. The new framework is solely based on future-reward vectors associated with future policies, which is more parsimonious than the traditional framework based on belief vectors. It reveals the connection between the POMDP problem and two computational geometry problems, i.e., finding the vertices of a convex hull and finding the Minkowski sum of convex polytopes, which can help solve the POMDP problem more efficiently. The new framework can clarify some existing algorithms over both finite and infinite horizons and shed new light on them. It also facilitates the comparison of POMDPs with respect to their degree of observability, as a useful structural result. © 2010 INFORMS.


Pang R.D.,University of Southern California
Experimental and clinical psychopharmacology | Year: 2013

Heightened negative affect during acute tobacco abstinence in women relative to men could be an important factor underlying sex differences in smoking motivation. However, little controlled experimental work addresses this hypothesis. The current study investigated sex differences in withdrawal-related negative affect, time to start smoking on a lab analogue smoking lapse task, and the interrelation between sex, withdrawal-related negative affect, and smoking lapse behavior. Following a baseline session, current smokers (women: n = 68, men: n = 131) attended two counterbalanced lab sessions (16 hours smoking abstinence and ad libitum smoking) during which they completed self-report measures of mood and withdrawal symptoms followed by a laboratory analogue smoking lapse task. In this task participants are monetarily rewarded for delaying smoking. Performance on this task serves as an analogue model of smoking lapse behavior by measuring smoker's capability to resist temptation to smoke under conditions where abstinence is advantageous. Females showed greater abstinence induced increases in composite negative affect as well as several particular negative affect states (i.e., POMS Anger, Anxiety, Depression, and Confusion, ps < .05) but no differences in abstinence induced changes in other forms of affect or craving. Females also exhibited marginally greater abstinence induced decreases in their willingness to delay smoking for money (p = .10), which was mediated by abstinence induced increases in anger (p < .05). These results suggest that differential sensitivity to abstinence induced negative affect, particularly anger, could underlie sex specific smoking patterns. Negative affect during tobacco abstinence may be an important factor for understanding and treating nicotine addiction in women. PsycINFO Database Record (c) 2013 APA, all rights reserved


Laird P.W.,University of Southern California
Nature Reviews Genetics | Year: 2010

Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. Therefore, profiling DNA methylation across the genome is vital to understanding the influence of epigenetics. There has been a revolution in DNA methylation analysis technology over the past decade: analyses that previously were restricted to specific loci can now be performed on a genome-scale and entire methylomes can be characterized at single-base-pair resolution. However, there is such a diversity of DNA methylation profiling techniques that it can be challenging to select one. This Review discusses the different approaches and their relative merits and introduces considerations for data analysis. © 2010 Macmillan Publishers Limited. All rights reserved.


Thomas D.,University of Southern California
Nature Reviews Genetics | Year: 2010

Despite the yield of recent genome-wide association (GWA) studies, the identified variants explain only a small proportion of the heritability of most complex diseases. This unexplained heritability could be partly due to geneĝ€"environment (GÃ-E) interactions or more complex pathways involving multiple genes and exposures. This Review provides a tutorial on the available epidemiological designs and statistical analysis approaches for studying specific GÃ-E interactions and choosing the most appropriate methods. I discuss the approaches that are being developed for studying entire pathways and available techniques for mining interactions in GWA data. I also explore methods for marrying hypothesis-driven pathway-based approaches with 'agnostic' GWA studies. © 2010 Macmillan Publishers Limited. All rights reserved.


Ailshire J.A.,University of Southern California | Clarke P.,University of Michigan
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2015

Objectives. There is growing interest in understanding how exposures in the residential environment relate to cognitive function in older adults. The goal of this study is to determine if neighborhood-level exposure to fine particulate matter air pollution (PM2.5) is associated with cognitive function in a diverse, national sample of older U.S. adults. Methods. We use cross-sectional data on non-Hispanic black and white men and women aged 55 and older from the 2001/2002 Americans' Changing Lives Study (N = 780). EPA air monitoring data were linked to respondents using census tract identifiers. Cognitive function was assessed with tests of working memory and orientation. Negative binomial regression models were used to examine the association between PM2.5 and the number of errors on the cognitive assessment. Results. Older adults living in areas with high concentrations of PM2.5 had an error rate 1.5 times greater than those exposed to lower concentrations, net of individual and neighborhood-level demographic and socioeconomic characteristics. Discussion. This study adds to a growing body of research demonstrating the importance of air pollution to cognitive function in older adults. Improvements to air quality may be an important mechanism for reducing age-related cognitive decline. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.


Zhu L.,Saint Louis University | Ben-Zion Y.,University of Southern California
Geophysical Journal International | Year: 2013

We decompose a general seismic potency tensor into isotropic tensor, double-couple tensor and compensated linear vector dipole using the eigenvectors and eigenvalues of the full tensor. Two dimensionless parameters are used to quantify the size of the isotropic and compensated linear vector dipole components. The parameters have well-defined finite ranges and are suited for non-linear inversions of source tensors from seismic waveform data. The decomposition and parametrization for the potency tensor are used to obtain corresponding results for a general seismic moment tensor. The relations between different parameters of the potency and moment tensors in isotropic media are derived. We also discuss appropriate specification of the relative size of different source components in inversions of seismic data. © The Authors 2013.


Heller M.M.,University of Southern California
Skin therapy letter | Year: 2011

Emotional stress may influence the development and exacerbation of psoriasis. The proportion of psoriasis patients who believe stress affects their skin condition (i.e., "stress responders") is considerably high, ranging from 37% to 78%. Stress may worsen psoriasis severity and may even lengthen the time to disease clearance. Although a pathogenic association appears likely, additional well-controlled studies are necessary to confirm such a causal relationship. Dysregulation of the hypothalamus-pituitary-adrenal and sympathetic adrenomedullary systems has been proposed as one possible underlying cause of stress-induced flares of psoriasis. While stress may be an exacerbating factor, psoriasis itself may contribute to significant adverse psychological sequelae. Breaking this stress cycle may be an important part of any therapeutic approach. Thus, stress reduction through psychotherapy and pharmacotherapy may be useful in treating psoriatic patients who are stress responders.


Nuzhdin S.V.,University of Southern California | Turner T.L.,University of California at Santa Barbara
Current Opinion in Genetics and Development | Year: 2013

Building the connection between genetic and phenotypic variation is an important 'work in progress', and one that will enable proactive diagnosis and treatment in medicine, promote development of environment-targeted varieties in agriculture, and clarify the limits of species adaptation to changing environments in conservation. Quantitative trait loci (QTL) mapping and genome wide association (GWA) studies have recently been allied to an additional focus on 'hitchhiking' (HH) mapping - using changes in allele frequency due to artificial or natural selection. This older technique has been popularized by the falling costs of high throughput sequencing. Initial HH-resequensing experiments seem to have found many thousands of polymorphisms responding to selection. We argue that this interpretation appears too optimistic, and that the data might in fact be more consistent with dozens, rather than thousands, of loci under selection. We propose several developments required for sensible data analyses that will fully realize the great power of the HH technique, and outline ways of moving forward. © 2013 Elsevier Ltd.


Brutchey R.L.,University of Southern California
Accounts of Chemical Research | Year: 2015

The ability to synthesize colloidal semiconductor nanocrystals in a well-controlled manner (i.e., with fine control over size, shape, size dispersion, and composition) has been mastered over the past 15 years. Much of this success stems from careful studies of precursor conversion and nanocrystal growth with respect to phosphine chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals. Despite the high level of success that has been achieved with phosphine chalcogenides, there has been a longstanding interest in exploring alternate chalcogenide precursors because of issues associated with phosphine chalcogenide cost, purity, toxicity, etc. This has resulted in a large body of literature on the use of sulfur and selenium dissolved in octadecene or amines, thio- and selenoureas, and silyl chalcogenides as alternate chalcogenide precursors for metal chalcogenide nanocrystal synthesis.In this Account, emerging work on the use of diorganyl dichalcogenides (R-E-E-R, where E = S, Se, or Te and R = alkyl, allyl, benzyl, or aryl) as alternate chalcogenide precursors for the synthesis of metal chalcogenide nanocrystals is summarized. Among the benefits of these dichalcogenide synthons are the following: (i) they represent the first and only common precursor type that can function as chalcogen transfer reagents for each of the group VI elements (i.e., to make metal oxide, metal sulfide, metal selenide, and metal telluride nanocrystals); (ii) they possess relatively weak E-E bonds that can be readily cleaved under mild thermolytic or photolytic conditions; and (iii) the organic substituents can be tuned to affect the reactivity. These combined attributes have allowed dichalcogenide precursors to be employed for a wide range of metal chalcogenide nanocrystal syntheses, including those for In2S3, SnxGe1-xSe, SnTe, Cu2-xSySe1-y, ZnSe, CdS, CdSe, MoSe2, WSe2, BiSe, and CuFeS2. Interestingly, a number of metastable phases of compositionally complex semiconductors can be kinetically accessed through syntheses utilizing dichalcogenide precursors, likely as a result of their ability to convert at relatively low temperatures. These include the hexagonal wurtzite phases of CuInS2, CuInSe2, Cu2ZnSn(S1-xSex)4, and Cu2SnSe3 nanocrystals. The discovery of crystal phases on the nanoscale that do not exist in their bulk analogues is a developing area of nanocrystal chemistry, and dichalcogenides are proving to be a useful synthetic tool in this regard.The most recent application of dichalcogenide synthons for semiconductor nanocrystals is their use as precursors for surface ligands. While there is a rich history of using thiol ligands for semiconductor nanocrystals, the analogous selenol and tellurol ligands have not been studied, likely because of their oxidative instability. Dichalcogenides have proven useful in this regard, as they can be reduced in situ with diphenylphosphine to give the corresponding selenol or tellurol ligand that binds to the nanocrystal surface. This chemistry has been applied to the in situ synthesis and ligand binding of selenols to PbSe nanocrystals and both selenols and tellurols to CdSe nanocrystals. These initial studies have allowed the photophysics of these nanocrystal-ligand constructs to be investigated; in both cases, it appears that the selenol and tellurol ligands act as hole traps that quench the photoluminescence of the semiconductor nanocrystals. © 2015 American Chemical Society.


Tahmasebi P.,Stanford University | Sahimi M.,University of Southern California
Physical Review Letters | Year: 2013

Porous media, heterogeneous materials, and biological tissues are examples of ubiquitous disordered systems, the understanding of which and any physical phenomenon in them entails having an accurate model. We show that a new reconstruction method based on a cross-correlation function and a one-dimensional raster path provides an accurate description of a wide variety of such materials and media. The reconstruction uses a single 2D slice of data to reconstruct an entire 3D medium. Seventeen examples are reconstructed accurately, as indicated by two connectivity functions that we compute for them. The reconstruction method may be used for both unconditioned and conditioned problems, and is highly efficient computationally. © 2013 American Physical Society.


Hunt H.K.,University of Missouri | Armani A.M.,University of Southern California
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2014

Whispering gallery mode optical microcavities have significantly impacted the field of label-free optical biodetection. By combining the evanescent field generated by the microcavity with biomimetic surface chemistries, it is now possible to use the microcavities as not only biosensors, but as analytical tools to explore fundamental chemical and physical interactions of biomolecules and biomaterials. Here, we review the recent advancements of these applications from a surface chemistry perspective. For example, surface chemistries can be generated from a standard coating perspective, where active molecules, such as laser or fluorescent dyes can be embedded in a biomaterial matrix. Alternatively, direct and reverse grafting techniques can be used to tether biomolecules of interest to the surface to tune the surface properties (hydrophobicity/hydrophilicity, protein adsorption, cell adhesion, etc.). Finally, we discuss how to apply advancements in biomimetic chemistry from other sensor approaches to these devices to continue the development of new analytical tools. All of these developments rely on a firm understanding of how proper surface chemistries can be merged with whispering gallery mode optical microcavities to achieve not just a platform, but a precisely defined tool for a given application. © 2013 IEEE.


O'Leary D.E.,University of Southern California
IEEE Intelligent Systems | Year: 2013

AI has been used in several different ways to facilitate capturing and structuring big data, and AI has been used to analyze big data for key insights. Some of the basic concerns and uses are examined here, while future articles will present case studies that analyze emerging issues and approaches integrating AI and big data. © 2001-2011 IEEE.


Cannon P.,University of Southern California | June C.,University of Pennsylvania
Current Opinion in HIV and AIDS | Year: 2011

CCR5 gene knockout in T cells or HSCs by ZFNs effectively suppresses the replication of CCR5-tropic strains of HIV-1 in animal models. ZFNs are currently being evaluated in a phase I clinical trials using ex vivo expanded T cells and HSCs targeted therapies are under development. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Crimmins E.M.,University of Southern California
Gerontologist | Year: 2015

The past century was a period of increasing life expectancy throughout the age range. This resulted in more people living to old age and to spending more years at the older ages. It is likely that increases in life expectancy at older ages will continue, but life expectancy at birth is unlikely to reach levels above 95 unless there is a fundamental change in our ability to delay the aging process. We have yet to experience much compression of morbidity as the age of onset of most health problems has not increased markedly. In recent decades, there have been some reductions in the prevalence of physical disability and dementia. At the same time, the prevalence of disease has increased markedly, in large part due to treatment which extends life for those with disease. Compressing morbidity or increasing the relative healthspan will require "delaying aging" or delaying the physiological change that results in disease and disability. While moving to life expectancies above age 95 and compressing morbidity substantially may require significant scientific breakthroughs; significant improvement in health and increases in life expectancy in the United States could be achieved with behavioral, life style, and policy changes that reduce socioeconomic disparities and allow us to reach the levels of health and life expectancy achieved in peer societies. © The Author 2015.


Yen J.T.,University of Southern California
Journal of the Acoustical Society of America | Year: 2013

Fully-sampled two-dimensional (2D) arrays can have two-way focusing of the ultrasound beam in both lateral directions leading to high quality, real-time three-dimensional (3D) imaging. However, fully-sampled 2D arrays with very large element counts (>16 000) are difficult to manufacture due to interconnect density and large element electrical impedance. As an alternative, row-column or crossed electrode arrays have been proposed to simplify transducer fabrication and system integration. These types of arrays consist of two one-dimensional arrays oriented perpendicular to each other. Using conventional delay-and-sum beamforming, each array performs one-way focusing in perpendicular lateral directions which yield higher sidelobe and acoustic clutter levels compared to fully-sampled 2D arrays with two-way focusing. In this paper, the use of spatial matched filters to improve focusing of row-column arrays is investigated. On receive, data from each element are first spatial match filtered in the elevation direction. After summation, the data are filtered again in the azimuth direction. Beam widths comparable to one-way focusing are seen in azimuth and beam widths comparable to two-way focusing are achieved in elevation. 3D beam patterns from computer simulation results using a 7.5 MHz 128 × 128 row-column array are shown with comparison to a fully sampled 2D array. © 2013 Acoustical Society of America.


Hoh D.J.,University of Southern California
Neurosurgery | Year: 2010

BACKGROUND: Intermuscular approaches can expose the lumbar spine and minimize muscular trauma and injury. The segmental anatomy of the posterior lumbar musculature allows surgical access through separation of muscle groups and fascicles and provides one to develop intermuscular working channels while preserving the integrity of the muscles and their function. In addition, preservation of the accompanying neurovascular bundles minimizes blood loss, tissue atrophy, and pain. With these approaches, a variety of procedures for decompression, discectomy, interbody fusion, or pedicle screw fixation can be achieved for single or multiple levels without subperiosteal stripping or muscle transection. OBJECTIVE: A detailed description of the relevant surgical anatomy for the muscle-sparing approach to the lumbar spine.


Varma R.,University of Southern California
Neurology | Year: 2013

Vision is a sensation that is created from complex processes and provides us with a representation of the world around us. There are many important aspects of vision, but visual acuity was judged to be the most appropriate vision assessment for the NIH Toolbox for Assessment of Neurological and Behavioral Function, both because of its central role in visual health and because acuity testing is common and relatively inexpensive to implement broadly. The impact of visual impairments on health-related quality of life also was viewed as important to assess, in order to gain a broad view of one's visual function. To test visual acuity, an easy-to-use software program was developed, based on the protocol used by the E-ETDRS. Children younger than 7 years were administered a version with only the letters H, O, T, and V. Reliability and validity of the Toolbox visual acuity test were very good. A 53-item vision-targeted, health-related quality of life survey was also developed.


Long M.D.,Yale University | Becker T.W.,University of Southern California
Earth and Planetary Science Letters | Year: 2010

Observations of seismic anisotropy yield some of the most direct constraints available on both past and present-day deformation in the Earth's mantle. Insight into the character of mantle flow can also be gained from the geodynamical modeling of mantle processes on both global and regional scales. We highlight recent progress toward understanding mantle flow from both observations and modeling and discuss outstanding problems and avenues for progress, particularly in the integration of seismological and geodynamical constraints to understand seismic anisotropy and the deformation that produces it. To first order, the predictions of upper mantle anisotropy made by global mantle circulation models match seismological observations well beneath the ocean basins, but the fit is poorer in regions of greater tectonic complexity, such as beneath continental interiors and within subduction systems. In many regions of the upper mantle, models of anisotropy derived from surface waves are seemingly inconsistent with shear wave splitting observations, which suggests that our understanding of complex anisotropic regions remains incomplete. Observations of anisotropy in the D" layer hold promise for improving our understanding of dynamic processes in the deep Earth but much progress remains to be made in characterizing anisotropic structure and relating it to the geometry of flow, geochemical heterogeneity, or phase transitions. Major outstanding problems related to understanding mantle anisotropy remain, particularly regarding the deformation and evolution of continents, the nature of the asthenosphere, subduction zone geodynamics, and the thermo-chemical state of the lowermost mantle. However, we expect that new seismological deployments and closer integration of observations with geodynamical models will yield rapid progress in these areas. © 2010 Elsevier B.V.


Watanabe R.M.,University of Southern California
Genome Medicine | Year: 2011

Despite years of investigation, very little is known about the genetic predisposition for gestational diabetes mellitus (GDM). However, the advent of genome-wide association and identification of loci contributing to susceptibility to type 2 diabetes mellitus has opened a small window into the genetics of GDM. More importantly, the study of the genetics of GDM has not only illuminated potential new biology underlying diabetes in pregnancy, but has also provided insights into fetal outcomes. Here, I review some of the insights into GDM and fetal outcomes gained through the study of both rare and common genetic variation. I also discuss whether recent testing of type 2 diabetes mellitus susceptibility loci in GDM case-control samples changes views of whether GDM is a distinct form of diabetes. Finally, I examine how the study of susceptibility loci can be used to influence clinical care, one of the great promises of the new era of human genome analysis. © 2011 BioMed Central Ltd.


Becker T.W.,University of Southern California | Faccenna C.,Third University of Rome
Earth and Planetary Science Letters | Year: 2011

Collisional belts are generated by the arrival of continental lithosphere into a subduction zone. The Tethyan suture from the Bitlis to the Himalayas is a prime example where the Arabian and Indian plates collided with Eurasia during the Cenozoic. While the kinematics of this process are well established, its dynamics are more uncertain. India and Arabia intriguingly keep advancing, in spite of large collisional resisting forces, and in the absence of a substantial, upper mantle slab driving force at present-day. We perform global mantle circulation computations to test the role of deep mantle flow as a driving force for the kinematics of the Tethyan collisional belt, evaluating different boundary conditions and mantle density distributions as inferred from seismic tomography or slab models. Our results show that mantle drag exerted on the base of the lithosphere by a large-scale, convective "conveyor belt" with an active upwelling component is likely the main cause for the ongoing indentation of the Indian and Arabian plates into Eurasia. © 2011 Elsevier B.V.


Recent years have seen an increased interest in developing culturally and linguistically responsive systems of care in substance abuse treatment in the United States. This study examines the extent to which external and internal organizational pressures contributed to the degree of adoption of culturally and linguistically responsive practices in the nation's outpatient substance abuse treatment system early in the period of development of this system of care. Findings show that a higher degree of adoption of culturally competent practices was most likely in treatment programs with high dependence on external funding and regulation. Internally, programs with a larger number of professionals were associated with the lowest degree of adoption, while managers' cultural sensitivity contributed significantly to a high degree of adoption of these responsive practices. Considering the passage of recent legislation enforcing the use of cultural and linguistic competence in health care, implications of these baseline findings on early adoption patterns are discussed for future research and health care policy evaluation. © 2011 Elsevier Ltd.


Arany Z.,University of Pennsylvania | Elkayam U.,University of Southern California
Circulation | Year: 2016

Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period and is marked by left ventricular dysfunction and heart failure. The disease is relatively uncommon, but its incidence is rising. Women often recover cardiac function, but long-lasting morbidity and mortality are not infrequent. Management of peripartum cardiomyopathy is largely limited to the same neurohormonal antagonists used in other forms of cardiomyopathy, and no proven disease-specific therapies exist yet. Research in the past decade has suggested that peripartum cardiomyopathy is caused by vascular dysfunction, triggered by late-gestational maternal hormones. Most recently, information has also indicated that many cases of peripartum cardiomyopathy have genetic underpinnings. We review here the known epidemiology, clinical presentation, and management of peripartum cardiomyopathy, as well as the current knowledge of the pathophysiology of the disease. © 2016 American Heart Association, Inc.


Kloner R.A.,University of Southern California
Journal of Cardiovascular Pharmacology and Therapeutics | Year: 2011

The no-reflow phenomenon relates to the inability to reperfuse regions of the myocardium after ischemia, despite removal of the large epicardial coronary artery occlusion. The mechanism involves microvascular obstruction. In experimental studies, using markers for flow (thioflavin S, carbon black, microspheres), perfusion defects associated with no-reflow demonstrated ultrastructural evidence of localized endothelial swelling and blebs that appeared to obstruct flow. In humans no-reflow is more complicated due to the microemboli of atherosclerotic debris and thrombi generated by percutaneous coronary intervention. The no-reflow zone expands during the first few hours of reperfusion suggesting an element of reperfusion injury. In animal models, extensive no-reflow was associated with worse infarct expansion. The phenomenon of no-reflow following reperfusion therapy for myocardial infarction in humans has been demonstrated by magnetic resonance imaging, echo contrast agents, thallium, technecium-99m-labeled albumin microspheres, Thrombolysis In Myocardial Infarction (TIMI) scores, and myocardial blush grade. Patients exhibiting no-reflow following reperfusion therapy for myocardial infarction have greater left ventricular dilation and remodeling, more congestive heart failure, shock, and reduced survival. Certain vasodilators (adenosine, nitroprusside, nicorandil, and calcium blockers) are used acutely in the catheterization laboratory and appear to improve no-reflow, but systematic studies on therapy for no-reflow are needed. There is now clinical evidence that no-reflow is a strong predictor of long-term mortality that is independent of and beyond that provided by infarct size. Identifying and treating no-reflow may have important benefits including enhancing delivery of nutrients and cells required for healing and reducing infarct expansion and ventricular remodeling, which ultimately may reduce congestive heart failure and mortality. © The Author(s) 2011.


Jena A.B.,Harvard University | Sun E.C.,Stanford University | Romley J.A.,University of Southern California
Circulation | Year: 2013

Background-Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect. Methods and Results-Using the US Nationwide Inpatient sample, we estimated difference-in-difference models of mortality, percutaneous coronary intervention rates, and bleeding complication rates, for high- and low-risk patients with acute myocardial infarction admitted to 98 teaching-intensive and 1353 non-teaching-intensive hospitals during May and July 2002 to 2008. Among patients in the top quartile of predicted acute myocardial infarction mortality (high risk), adjusted mortality was lower in May than July in teaching-intensive hospitals (18.8% in May, 22.7% in July, P>0.01), but similar in non-teaching-intensive hospitals (22.5% in May, 22.8% in July, P=0.70). Among patients in the lowest three quartiles of predicted acute myocardial infarction mortality (low risk), adjusted mortality was similar in May and July in both teaching-intensive hospitals (2.1% in May, 1.9% in July, P=0.45) and non-teaching-intensive hospitals (2.7% in May, 2.8% in July, P=0.21). Differences in percutaneous coronary intervention and bleeding complication rates could not explain the observed July mortality effect among high risk patients. Conclusions-High-risk acute myocardial infarction patients experience similar mortality in teaching- and non-teachingintensive hospitals in July, but lower mortality in teaching-intensive hospitals in May. Low-risk patients experience no such July effect in teaching-intensive hospitals.© 2013 American Heart Association, Inc.


Chen L.,University of Southern California
Statistics in Biosciences | Year: 2013

The burgeoning field of high-throughput sequencing significantly improves our ability to understand the complexity of transcriptomes. Alternative splicing, as one of the most important driving forces for transcriptome diversity, can now be studied at an unprecedent resolution. Efficient and powerful computational and statistical methods are in urgent need to facilitate the characterization and quantification of alternative splicing events. Here we discuss methods in splice junction read mapping, and methods in exon-centric or isoform-centric quantification of alternative splicing. In addition, we discuss HITS-CLIP and splicing QTL analyses which are novel high-throughput sequencing based approaches in the dissection of splicing regulation. © 2012 International Chinese Statistical Association.


Liang C.,University of Southern California
Cell Host and Microbe | Year: 2012

Tumor-causing γ-herpesviruses have evolved elaborate mechanisms to deal with almost every aspect of host cell defense. In this issue of Cell Host & Microbe, Leidal et al. (2012) report an oncogenic synergy between the latent KSHV proteins v-FLIP and v-cyclin during KSHV persistent infection that reshapes autophagy. © 2012 Elsevier Inc.


O'Connell C.,University of Southern California
Blood | Year: 2015

The identification of pulmonary embolism (PE) on computed tomography scans performed for indications other than identification of thromboembolism is a growing clinical problem that has not been adequately addressed by prospective treatment trials. The prevalence of incidentally detected PE ranges from 1% to 4% in unselected populations, with higher rates among hospital inpatients and patients with cancer. Current guidelines recommend using the same approach to type and duration of anticoagulation as is used for patients with suspected PE. Available data regarding the significance of symptomatic subsegmental PE (SSPE) are conflicting, making it difficult to draw conclusions about the appropriate treatment of incidentally detected SSPE, for which the data are sparse. Among cancer patients, the bulk of available data suggest that incidental SSPE is associated with recurrent venous thromboembolism and, when symptomatic, may adversely impact survival. Here, the topic is reviewed utilizing 3 clinical cases, each of which is followed by a discussion of salient features and then by treatment recommendations. © 2015 by The American Society of Hematology.


Toth Z.,University of Southern California
PLoS pathogens | Year: 2010

Epigenetic modifications of the herpesviral genome play a key role in the transcriptional control of latent and lytic genes during a productive viral lifecycle. In this study, we describe for the first time a comprehensive genome-wide ChIP-on-Chip analysis of the chromatin associated with the Kaposi's sarcoma-associated herpesvirus (KSHV) genome during latency and lytic reactivation. Depending on the gene expression class, different combinations of activating [acetylated H3 (AcH3) and H3K4me3] and repressive [H3K9me3 and H3K27me3] histone modifications are associated with the viral latent genome, which changes upon reactivation in a manner that is correlated with their expression. Specifically, both the activating marks co-localize on the KSHV latent genome, as do the repressive marks. However, the activating and repressive histone modifications are mutually exclusive of each other on the bulk of the latent KSHV genome. The genomic region encoding the IE genes ORF50 and ORF48 possesses the features of a bivalent chromatin structure characterized by the concomitant presence of the activating H3K4me3 and the repressive H3K27me3 marks during latency, which rapidly changes upon reactivation with increasing AcH3 and H3K4me3 marks and decreasing H3K27me3. Furthermore, EZH2, the H3K27me3 histone methyltransferase of the Polycomb group proteins (PcG), colocalizes with the H3K27me3 mark on the entire KSHV genome during latency, whereas RTA-mediated reactivation induces EZH2 dissociation from the genomic regions encoding IE and E genes concurrent with decreasing H3K27me3 level and increasing IE/E lytic gene expression. Moreover, either the inhibition of EZH2 expression by a small molecule inhibitor DZNep and RNAi knockdown, or the expression of H3K27me3-specific histone demethylases apparently induced the KSHV lytic gene expression cascade. These data indicate that histone modifications associated with the KSHV latent genome are involved in the regulation of latency and ultimately in the control of the temporal and sequential expression of the lytic gene cascade. In addition, the PcG proteins play a critical role in the control of KSHV latency by maintaining a reversible heterochromatin on the KSHV lytic genes. Thus, the regulation of the spatial and temporal association of the PcG proteins with the KSHV genome may be crucial for propagating the KSHV lifecycle.


Seeger R.C.,Saban Research Institute | Seeger R.C.,University of Southern California
Seminars in Cancer Biology | Year: 2011

Purpose: This review demonstrates the importance of immunobiology and immunotherapy research for understanding and treating neuroblastoma. Principal results: The first suggestions of immune system-neuroblastoma interactions came from in vitro experiments showing that lymphocytes from patients were cytotoxic for their own tumor cells and from evaluations of tumors from patients that showed infiltrations of immune system cells. With the development of monoclonal antibody (mAb) technology, a number of mAbs were generated against neuroblastoma cells lines and were used to define tumor associated antigens. Disialoganglioside (GD2) is one such antigen that is highly expressed by virtually all neuroblastoma cells and so is a useful target for both identification and treatment of tumor cells with mAbs. Preclinical research using in vitro and transplantable tumor models of neuroblastoma has demonstrated that cytotoxic T lymphocytes (CTLs) can specifically recognize and kill tumor cells as a result of vaccination or of genetic engineering that endows them with chimeric antigen receptors. However, CTL based clinical trials have not progressed beyond pilot and phase I studies. In contrast, anti-GD2 mAbs have been extensively studied and modified in pre-clinical experiments and have progressed from phase I through phase III clinical trials. Thus, the one proven beneficial immunotherapy for patients with high-risk neuroblastoma uses a chimeric anti-GD2 mAb combined with IL-2 and GM-CSF to treat patients after they have received intensive cyto-reductive chemotherapy, irradiation, and surgery. Ongoing pre-clinical and clinical research emphasizes vaccine, adoptive cell therapy, and mAb strategies. Recently it was shown that the neuroblastoma microenvironment is immunosuppressive and tumor growth promoting, and strategies to overcome this are being developed to enhance anti-tumor immunotherapy. Conclusions: Our understanding of the immunobiology of neuroblastoma has increased immensely over the past 40 years, and clinical translation has shown that mAb based immunotherapy can contribute to improving treatment for high-risk patients. Continued immunobiology and pre-clinical therapeutic research will be translated into even more effective immunotherapeutic strategies that will be integrated with new cytotoxic drug and irradiation therapies to improve survival and quality of life for patients with high-risk neuroblastoma. © 2011 Elsevier Ltd.


Patel N.,University of Southern California | Malik P.,MLC 7013
Journal of Biological Chemistry | Year: 2010

Sickle cell disease (SCD) is characterized by a prothrombotic state. Plasminogen activator inhibitor-1 (PAI-1) is known to modulate fibrinolysis, lung injury/fibrosis, and angiogenesis. However, its role in SCD is less understood, and the molecular mechanisms underlying increased PAI-1 are unknown. Herein, we show a novel link between PAI-1 and sickle erythropoiesis. Plasma PAI-1 levels were high in SCD patients at steady state and in two humanized sickle mouse models, with increased PAI-1 immunolabeling in sickle mouse lung, bronchial epithelial cells, alveolar macrophages, and pulmonary microvascular endothelial cells. Placenta growth factor (PlGF), released at high levels by sickle erythroblasts, induced PAI-1 expression in primary human pulmonary microvascular endothelial cells and monocytes through activation of c-Jun N-terminal kinase (JNK), NADPH oxidase, and hypoxia-inducible factor-1α (HIF-1α). Analysis of the human PAI-1 promoter revealed this induction was mediated by hypoxia-response element (HRE)-1, HRE-2, and distal activator protein (AP-1) sites. We also identify the involvement of c-Jun, c-Jun/c-Fos, and JunD, but not JunB, in binding with AP-1 sites of the PAI-1 promoter upon PlGF induction. Consistent with these findings, levels of PAI-1 were low in PlGF knock-out mice and sickle-PlGF knock-out mice; overexpression of PlGF in normal mice increased circulating PAI-1. In conclusion, we identify a novel mechanism of PAI-1 elevation in SCD. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Dean M.D.,University of Southern California
PLoS Genetics | Year: 2013

Seminal fluid proteins affect fertility at multiple stages in reproduction. In many species, a male's ejaculate coagulates to form a copulatory plug. Although taxonomically widespread, the molecular details of plug formation remain poorly understood, limiting our ability to manipulate the structure and understand its role in reproduction. Here I show that male mice knockouts for transglutaminase IV (Tgm4) fail to form a copulatory plug, demonstrating that this gene is necessary for plug formation and lending a powerful new genetic tool to begin characterizing plug function. Tgm4 knockout males show normal sperm count, sperm motility, and reproductive morphology. However, very little of their ejaculate migrates into the female's reproductive tract, suggesting the plug prevents ejaculate leakage. Poor ejaculate migration leads to a reduction in the proportion of oocytes fertilized. However, Tgm4 knockout males fertilized between 3-11 oocytes, which should be adequate for a normal litter. Nevertheless, females mated to Tgm4 knockout males for approximately 14 days were significantly less likely to give birth to a litter compared to females mated to wild-type males. Therefore, it appears that the plug also affects post-fertilization events such as implantation and/or gestation. This study shows that a gene influencing the viscosity of seminal fluid has a major influence on male fertility. © 2013 Matthew D.


Serhan C.N.,Brigham and Womens Hospital | Petasis N.A.,University of Southern California
Chemical Reviews | Year: 2011

The key role of a number of lipid mediators in the initiation of the inflammatory response and the subsequent progression toward resolution is described. Despite its critical host-protective function, acute inflammation is not sustainable over a prolonged period of time, giving rise to disruptive conditions of chronic inflammation that may be responsible for the pathogenesis of a wide range of diseases that can be attributed to a failure of resolution. Activation of these receptors by these lipids directly affects the expression levels of multiple enzymes, chemokines, cytokines, and growth factors that play dominant roles in inflammation and resolution. The discovery of resolvins, protectins, and maresins is of particular significance, since these potent lipid mediators provided the first molecular basis for the many health benefits attributed to the omega-3 fatty acids EPA and DHA, which are abundant in fish and are widely used as dietary supplements.


Schneider L.S.,University of Southern California
Alzheimer's and Dementia | Year: 2014

The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. © 2014 The Alzheimers Association. All rights reserved.


Goodman M.F.,University of Southern California | Woodgate R.,U.S. National Institutes of Health
Cold Spring Harbor Perspectives in Biology | Year: 2013

Living cells are continually exposed to DNA-damaging agents that threaten their genomic integrity. Although DNA repair processes rapidly target the damaged DNA for repair, some lesions nevertheless persist and block genome duplication by the cell's replicase. To avoid the deleterious consequence of a stalled replication fork, cells use specialized polymerases to traverse the damage. This process, termed "translesion DNA synthesis" (TLS), affords the cell additional time to repair the damage before the replicase returns to complete genome duplication. In many cases, this damage-tolerance mechanism is error-prone, and cell survival is often associated with an increased risk of mutagenesis and carcinogenesis. Despite being tightly regulated by a variety of transcriptional and posttranslational controls, the low-fidelity TLS polymerases also gain access to undamaged DNA where their inaccurate synthesis may actually be beneficial for genetic diversity and evolutionary fitness. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.


Bravaya K.B.,University of Southern California
Accounts of chemical research | Year: 2012

The unique properties of green fluorescent protein (GFP) have been harnessed in a variety of bioimaging techniques, revolutionizing many areas of the life sciences. Molecular-level understanding of the underlying photophysics provides an advantage in the design of new fluorescent proteins (FPs) with improved properties; however, because of its complexity, many aspects of the GFP photocycle remain unknown. In this Account, we discuss computational studies of FPs and their chromophores that provide qualitative insights into mechanistic details of their photocycle and the structural basis for their optical properties. In a reductionist framework, studies of well-defined model systems (such as isolated chromophores) help to understand their intrinsic properties, while calculations including protein matrix and/or solvent demonstrate, on the atomic level, how these properties are modulated by the environment. An interesting feature of several anionic FP chromophores in the gas phase is their low electron detachment energy. For example, the bright excited ππ* state of the model GFP chromophore (2.6 eV) lies above the electron detachment continuum (2.5 eV). Thus, the excited state is metastable with respect to electron detachment. This autoionizing character needs to be taken into account in interpreting gas-phase measurements and is very difficult to describe computationally. Solvation (and even microsolvation by a single water molecule) stabilizes the anionic states enough such that the resonance excited state becomes bound. However, even in stabilizing environments (such as protein or solution), the anionic chromophores have relatively low oxidation potentials and can act as light-induced electron donors. Protein appears to affect excitation energies very little (<0.1 eV), but alters ionization or electron detachment energies by several electron volts. Solvents (especially polar ones) have a pronounced effect on the chromophore's electronic states; for example, the absorption wavelength changes considerably, the ground-state barrier for cis-trans isomerization is reduced, and fluorescence quantum yield drops dramatically. Calculations reveal that these effects can be explained in terms of electrostatic interactions and polarization, as well as specific interactions such as hydrogen bonding. The availability of efficient computer implementations of predictive electronic structure methods is essential. Important challenges include developing faster codes (to enable better equilibrium sampling and excited-state dynamics modeling), creating algorithms for properties calculations (such as nonlinear optical properties), extending standard excited-state methods to autoionizing (resonance) states, and developing accurate QM/MM schemes. The results of sophisticated first-principle calculations can be interpreted in terms of simpler, qualitative molecular orbital models to explain general trends. In particular, an essential feature of the anionic GFP chromophore is an almost perfect resonance (mesomeric) interaction between two Lewis structures, giving rise to charge delocalization, bond-order scrambling, and, most importantly, allylic frontier molecular orbitals spanning the methine bridge. We demonstrate that a three-center Hückel-like model provides a useful framework for understanding properties of FPs. It can explain changes in absorption wavelength upon protonation or other structural modifications of the chromophore, the magnitude of transition dipole moment, barriers to isomerization, and even non-Condon effects in one- and two-photon absorption.


Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in >200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA in 2010, experience of HAL–BLC in the USA continues to expand. To define areas of need and to identify the benefits of HAL–BLC in clinical practice, a focus group of expert urologists specializing in the management of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a consensus regarding the optimal use of HAL–BLC in the USA. The focus group concluded that HAL–BLC should be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with positive urine cytology but negative WLC findings, and for tumour staging.


Spencer C.,University of Southern California | Fatemi S.,Kaiser Permanente
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

Thyroglobulin autoantibodies (TgAb) are detected at diagnosis or during treatment in approximately 25% of patients with differentiated thyroid cancer (DTC). When present, TgAb interferes with thyroglobulin (Tg) measurement causing falsely low or undetectable Tg immunometric assay (IMA) values that can mask disease. Guidelines mandate that every Tg test have TgAb measured simultaneously and quantitatively by immunoassay and not a recovery test. The propensity and magnitude of TgAb-Tg interference relates to both Tg and TgAb concentrations and the class of Tg method used. Because the TgAb trend reflects changes in thyroid tissue mass, TgAb concentrations serve as a surrogate post-operative DTC tumor marker. A rising, or de novo appearance of TgAb may indicate recurrence, whereas a progressive decline suggests successful treatment. This review focuses on the technical limitations of current TgAb methods, characteristics of TgAb interference with different classes of Tg method, and the clinical value of monitoring TgAb trends as a surrogate DTC tumor marker. © 2013 Elsevier Ltd. All rights reserved.


Schonthal A.H.,University of Southern California
Molecular Nutrition and Food Research | Year: 2011

A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet underappreciated risks. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Lange B.,University of Southern California
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference | Year: 2011

The use of the commercial video games as rehabilitation tools, such as the Nintendo WiiFit, has recently gained much interest in the physical therapy arena. Motion tracking controllers such as the Nintendo Wiimote are not sensitive enough to accurately measure performance in all components of balance. Additionally, users can figure out how to "cheat" inaccurate trackers by performing minimal movement (e.g. wrist twisting a Wiimote instead of a full arm swing). Physical rehabilitation requires accurate and appropriate tracking and feedback of performance. To this end, we are developing applications that leverage recent advances in commercial video game technology to provide full-body control of animated virtual characters. A key component of our approach is the use of newly available low cost depth sensing camera technology that provides markerless full-body tracking on a conventional PC. The aim of this research was to develop and assess an interactive game-based rehabilitation tool for balance training of adults with neurological injury.


Chen K.,University of Southern California | Chen X.,U.S. National Institutes of Health
Seminars in Oncology | Year: 2011

Positron emission tomography (PET) is one of the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. The principal goal of PET imaging is to visualize, characterize, and measure biological processes at the cellular, subcellular, and molecular levels in living subjects using noninvasive procedures. PET imaging takes advantage of the traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer progression. Although [ 18F]fluorodeoxyglucose ([18F]FDG)-PET has been widely utilized for staging and restaging of cancer, evaluation of response to treatment, differentiation of post-therapy alterations from residual or recurrent tumor, and assessment of prognosis, [18F]FDG is not a target-specific PET tracer. Over the last decade, numerous target-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current status and trends in the development of non-[18F]FDG PET probes in oncology and their application in the investigation of cancer biology. © 2011 Elsevier Inc. All rights reserved.


Niehoff B.E.,University of Southern California
Journal of High Energy Physics | Year: 2014

Abstract: We find an infinite class of non-supersymmetric multi-center solutions to the STU model in five-dimensional ungauged supergravity coupled to two vector multiplets. The solutions are obtained by solving a system of linear equations on a class of Ricci-scalar-flat Kähler manifolds studied by LeBrun. After imposing an additional U(1) isometry in the base, we solve the axisymmetric SU(∞) Toda equation and obtain explicit supergravity solutions containing arbitrary numbers of 2-cycles with cohomological fluxes of all three flavors. This improves upon a previous result where only two of the three fluxes were topologically non-trivial. Imposing regularity and absence of closed timelike curves, we obtain “bubble equations” highly reminiscent of those known in the supersymmetric case. Thus we extend much of the analysis done for BPS bubbling solutions to this new family of non-supersymmetric bubbling solutions. © 2014, The Author(s).


Yinying X.-L.,University of Southern California
Optics Express | Year: 2010

We present a design of a slot waveguide in which the core layer is orthogonally slotted to form a rectangular sub-core. While the overall guiding and coupling efficiency remains the same as a conventional slot waveguide, the field confinement is enhanced and appears two-dimensional. The waveguiding is controllable by selecting the intermediate index as well as various geometrical parameters. In addition, by changing different variables, the linear/nonlinear dispersion and birefringence can be tailored with extended ranges. Constant-dispersion points, where the dispersion is insensitive to size changes, are also demonstrated. © 2010 Optical Society of America.


Dhillon H.S.,University of Southern California | Andrews J.G.,University of Texas at Austin
IEEE Wireless Communications Letters | Year: 2014

Considering both small-scale fading and long-term shadowing, we characterize the downlink rate distribution at a typical user equipment (UE) in a heterogeneous cellular network (HetNet), where shadowing, following any general distribution, impacts cell selection while fading does not. Most prior work either ignores the impact of channel randomness on cell selection or lumps all the sources of randomness into a single variable, with cell selection based on the instantaneous signal strength, which is unrealistic. As an application of the results, we study the impact of shadowing on load balancing in terms of the optimal per-tier selection bias needed for rate maximization. © 2012 IEEE.


Gill A.,University of California at Los Angeles | Shellock F.G.,University of Southern California
Journal of Cardiovascular Magnetic Resonance | Year: 2012

Purpose. Metallic skin closure staples and vessel ligation clips should be tested at 3-Tesla to characterize MRI issues in order to ensure patient safety. Therefore, metallic surgical implants were assessed at 3-Tesla for magnetic field interactions, MRI-related heating, and artifacts. Methods. A skin closure staple (Visistat Skin Stapler, staple, Polytetrafluoroethylene, PTFE, coated 316L/316LVM stainless steel; Teleflex Medical, Durham, NC) and a vessel ligation clip (Hemoclip Traditional, stainless steel; Teleflex Medical, Durham, NC) that represented the largest metallic sizes made from materials with the highest magnetic susceptibilities (i.e., based on material information) among 61 other surgical implants (52 metallic implants, 9 nonmetallic implants) underwent evaluation for magnetic field interactions, MRI-related heating, and artifacts using standardized techniques. MRI-related heating was assessed by placing each implant in a gelled-saline-filled phantom with MRI performed using a transmit/receive RF body coil at an MR system reported, whole body averaged SAR of 2.9-W/kg for 15-min. Artifacts were characterized using T1-weighted, SE and GRE pulse sequences. Results: Each surgical implant showed minor magnetic field interactions (20- and 27-degrees, which is acceptable from a safety consideration). Heating was not substantial (highest temperature change, 1.6°C). Artifacts may create issues if the area of interest is in the same area or close to the respective surgical implant. Conclusions: The results demonstrated that it would be acceptable for patients with these metallic surgical implants to undergo MRI at 3-Tesla or less. Because of the materials and dimensions of the surgical implants that underwent testing, these findings pertain to 61 additional similar implants. © 2012 Gill and Shellock; licensee BioMed Central Ltd.


18F-Fluorodeoxyglucose avidity for gastroenteropancreatic neuroendocrine tumors and hepatocellular carcinoma is variable, depending on the underlying tumor biology. Experience with non-fluorodeoxyglucose (FDG) tracers (eg, 18F-labeled amine precursors l-dihydroxyphenylalanine and 68Ga-DOTA-peptides for gastroenteropancreatic neuroendocrine tumors and radiolabeled acetate or choline for hepatocellular carcinoma) is evolving and expanding rapidly. This article reviews the role of FDG and non-FDG radiotracers in the imaging evaluation of patients with gastroenteropancreatic neuroendocrine tumors or hepatocellular carcinoma. © 2012 Elsevier Inc. All rights reserved.


Galstyan A.,University of Southern California
Autonomous Agents and Multi-Agent Systems | Year: 2013

The problem of multi-agent learning and adaptation has attracted a great deal of attention in recent years. It has been suggested that the dynamics of multi agent learning can be studied using replicator equations from population biology. Most existing studies so far have been limited to discrete strategy spaces with a small number of available actions. In many cases, however, the choices available to agents are better characterized by continuous spectra. This paper suggests a generalization of the replicator framework that allows to study the adaptive dynamics of Q-learning agents with continuous strategy spaces. Instead of probability vectors, agents' strategies are now characterized by probability measures over continuous variables. As a result, the ordinary differential equations for the discrete case are replaced by a system of coupled integral-differential replicator equations that describe the mutual evolution of individual agent strategies. We derive a set of functional equations describing the steady state of the replicator dynamics, examine their solutions for several two-player games, and confirm our analytical results using simulations. © 2011 The Author(s).


Crimmins E.M.,University of Southern California
The journals of gerontology. Series B, Psychological sciences and social sciences | Year: 2011

This study examines the similarity of cognitive assessments using 1 interview in a large population study, the Health and Retirement Study (HRS), and a subsample in which a detailed neuropsychiatric assessment has been performed (Aging, Demographics, and Memory Study [ADAMS]). Respondents are diagnosed in ADAMS as demented, cognitively impaired without dementia (CIND), or as having normal cognitive function. Multinomial logistic analysis is used to predict diagnosis using a variety of cognitive and noncognitive measures from the HRS and additional measures and information from ADAMS. The cognitive tests in HRS predict the ADAMS diagnosis in 74% of the sample able to complete the HRS survey on their own. Proxy respondents answer for a large proportion of HRS respondents who are diagnosed as demented in ADAMS. Classification of proxy respondents with some cognitive impairment can be predicted in 86% of the sample. Adding a small number of additional tests from ADAMS can increase each of these percentages to 84% and 93%, respectively. Cognitive assessment appropriate for diagnosis of dementia and CIND in large population surveys could be improved with more targeted information from informants and additional cognitive tests targeting other areas of brain function.


Johnson C.V.,University of Southern California
Journal of High Energy Physics | Year: 2014

Holographic studies of the entanglement entropy of field theories dual to charged and neutral black holes in asymptotically global AdS4 spacetimes are presented. The goal is to elucidate various properties of the quantity that are peculiar to working in finite volume, and to gain access to the behaviour of the entanglement entropy in the rich thermodynamic phase structure that is present at finite volume and large N. The entropy is followed through various first order phase transitions, and also a novel second order phase transition. Properties of a specific heat in the neighbourhood of the critical point are computed. Behaviour is found that contrasts interestingly with an earlier holographic study of a second order phase transition dual to an holographic superconductor. © 2014 The Author(s).


Paetznick A.,University of Waterloo | Reichardt B.W.,University of Southern California
Physical Review Letters | Year: 2013

Transversal implementations of encoded unitary gates are highly desirable for fault-tolerant quantum computation. Though transversal gates alone cannot be computationally universal, they can be combined with specially distilled resource states in order to achieve universality. We show that "triorthogonal" stabilizer codes, introduced for state distillation by Bravyi and Haah, admit transversal implementation of the controlled-controlled- Z gate. We then construct a universal set of fault-tolerant gates without state distillation by using only transversal controlled-controlled-Z, transversal Hadamard, and fault-tolerant error correction. We also adapt the distillation procedure of Bravyi and Haah to Toffoli gates, improving on existing Toffoli distillation schemes. © 2013 American Physical Society.


Wang H.,University of Southern California
Proceedings of the Combustion Institute | Year: 2011

Over the last two decades, our understanding of soot formation has evolved from an empirical, phenomenological description to an age of quantitative modeling for at least small fuel compounds. In this paper, we review the current state of knowledge of the fundamental sooting processes, including the chemistry of soot precursors, particle nucleation and mass/size growth. The discussion shows that though much progress has been made, critical gaps remain in many areas of our knowledge. We propose the roles of certain aromatic radicals resulting from localized π electron structures in particle nucleation and subsequent mass growth. The existence of these free radicals provides a rational explanation for the strong binding forces needed for forming initial clusters of polycyclic aromatic hydrocarbons. They may also explain a range of currently unexplained sooting phenomena, including the large amount of aliphatics observed in nascent soot formed in laminar premixed flames and the mass growth of soot in the absence of gas-phase H atoms. While the above suggestions are inspired, to an extent, by recent theoretical findings from the materials research community, this paper also demonstrates that the knowledge garnered through our longstanding interest in soot formation may well be carried over to flame synthesis of functional nanomaterials for clean and renewable energy applications. In particular, work on flame-synthesized thin films of nanocrystalline titania illustrates how our combustion knowledge might be useful for developing advanced yet inexpensive thin-film solar cells and chemical sensors for detecting gaseous air pollutants. © 2010 Published by Elsevier Inc. on behalf of The Combustion Institute. All rights reserved.


Armony M.,New York University | Ward A.R.,University of Southern California
Operations Research | Year: 2010

We study a stochastic network that consists of two servers shared by two classes of jobs. Class 1 jobs require a concurrent occupancy of both servers while class 2 jobs use only one server. The traffic intensity is such that both servers are bottlenecks, meaning the service capacity is equal to the offered workload. The real-time allocation of the service capacity among the job classes takes the form of a solution to an optimization problem that maximizes a utility function. We derive the diffusion limit of the network and establish its asymptotic optimality. In particular, we identify a cost objective associated with the utility function and show that it is minimized at the diffusion limit by the utility-maximizing allocation within a broad class of "fair" allocation schemes. The model also highlights the key issues involved in multiple bottlenecks. © 2010 INFORMS.


Pavlou P.A.,Temple University | Sawy O.A.E.,University of Southern California
Information Systems Research | Year: 2010

Organizations are increasingly engaged in competitive dynamics that are enabled or induced by information technology (IT). A key competitive dynamics question for many organizations is how to build a competitive advantage in turbulence with digital IT systems. The literature has focused mostly on developing and exercising dynamic capabilities for planned reconfiguration of existing operational capabilities in fairly stable environments with patterned "waves," but this may not always be possible, or even appropriate, in highly turbulent environments with unexpected "storms." We introduce improvisational capabilities as an alternative means for managing highly turbulent environments; we define this as the ability to spontaneously reconfigure existing resources to build new operational capabilities to address urgent, unpredictable, and novel environmental situations. In contrast to the planned role of dynamic and operational capabilities and the ambidexterity that they jointly offer, improvisational capabilities are proposed to operate distinctly as a "third hand" that facilitates reconfiguration and change in highly turbulent environments. First, the paper develops the notion of improvisational capabilities and articulates the key differences between the two "reconfiguration"-improvisational and dynamic-capabilities. Second, the paper compares the relative effects of improvisational and dynamic capabilities in the context of new product development in different levels of environmental turbulence. Third, the paper shows how IT-leveraging capability in new product development is decomposed into its three digital IT systems: project and resource management systems, organizational memory systems (OMS), and cooperative work systems-and how each of these IT systems enhances improvisational capabilities, an effect that is accentuated in highly turbulent environments. The results show that although dynamic capabilities are the primary predictor of competitive advantage in moderately turbulent environments, improvisational capabilities fully dominate in highly turbulent environments. Besides discriminant validity, the distinction between improvisational and dynamic capabilities is evidenced by the differential effects of IT-leveraging capability on improvisational and dynamic capabilities. The results show that the more the IT-leveraging capability is catered toward managing resources (through project and resource management systems) and team collaboration (through cooperative work systems) rather than relying on past knowledge and procedures (through organizational memory systems), the more it is positively associated with improvisational capabilities, particularly in more turbulent environments. The paper draws implications for how different IT systems can influence improvisational capabilities and competitive advantage in turbulent environments, thereby enhancing our understanding of the role of IT systems on reconfiguration capabilities. The paper discusses the theoretical and practical implications of building and exercising the "third hand" of improvisational capabilities for IT-enabled competitive dynamics in turbulence. © 2010 INFORMS.


Chow B.Y.,University of California at San Diego | Kay S.A.,University of Southern California
Seminars in Cell and Developmental Biology | Year: 2013

The circadian clock is an endogenous timer that anticipates and synchronizes biological processes to the environment. Traditional genetic approaches identified the underlying principles and genetic components, but new discoveries have been greatly impeded by the embedded redundancies that confer necessary robustness to the clock architecture. To overcome this, global (omic) techniques have provided a new depth of information about the Arabidopsis clock. Our understanding of the factors, regulation, and mechanistic connectivity between clock genes and with output processes has substantially broadened through genomic (cDNA libraries, yeast one-hybrid, protein binding microarrays, and ChIP-seq), transcriptomic (microarrays, RNA-seq), proteomic (mass spectrometry and chemical libraries), and metabolomic (mass spectrometry) approaches. This evolution in research will undoubtedly enhance our understanding of how the circadian clock optimizes growth and fitness. © 2013 Elsevier Ltd.


Madni A.M.,University of Southern California
Systems Engineering | Year: 2012

Elegance is a term frequently associated with aesthetics in design. It typically connotes simplicity, beauty, and grace. When it comes to complex systems, it also connotes predictable behavior, power, and creative functionality. Elegance is what separates the merely functional from the engaging. An elegant design usually has a thematic vision that drives its creation. It engages both designers and users and supports creative exploration on their part. The process of elegant design is an iterative, creative process that exploits systems thinking, probing questioning, and appropriate analogies and metaphors to gain insights that can be transformed novel solutions. This paper provides key insights into elegant systems design and characteristics of elegant systems designers. It offers a heuristics-driven elegant systems design process along with metrics for assessing elegance. Copyright © 2012 Wiley Periodicals, Inc.


Weisenberger D.J.,University of Southern California
Journal of Clinical Investigation | Year: 2014

The Cancer Genome Atlas (TCGA) Research Network is an ambitious multi-institutional consortium effort aimed at characterizing sequence, copy number, gene (mRNA) expression, microRNA expression, and DNA methylation alterations in 30 cancer types. TCGA data have become an extraordinary resource for basic, translational, and clinical researchers and have the potential to shape cancer diagnostic and treatment strategies. DNA methylation changes are integral to all aspects of cancer genomics and have been shown to have important associations with gene expression, sequence, and copy number changes. This Review highlights the knowledge gained from DNA methylation alterations in human cancers from TCGA.


Jones P.A.,University of Southern California
Journal of Clinical Investigation | Year: 2014

The field of epigenetics has exploded in the last two decades, with incredible advances in recent years driven by high-throughput sequencing studies. Cancer cells frequently exhibit marked changes in DNA methylation and histone modification during tumorigenesis and tumor progression. These changes in the cancer epigenome are thought to be important in initiating and maintaining malignancy, and pharmaceutical approaches targeting epigenome- modifying enzymes are an attractive therapeutic strategy. Early successes have been made with DNA-demethylating drugs in hematologic malignancies, and efforts are underway to target additional epigenetic regulators and a broader array of tumor types. The Reviews in this issue of the JCI highlight ongoing efforts in this burgeoning field to translate our understanding of the cancer epigenome into successful interventional strategies in the clinic.


Rice E.,University of Southern California
AIDS and Behavior | Year: 2011

This study evaluates associations between online social networking and sexual health behaviors among homeless youth in Los Angeles. We analyzed survey data from 201 homeless youth accessing services at a Los Angeles agency. Multivariate (regression and logistic) models assessed whether use of (and topics discussed on) online social networking technologies affect HIV knowledge, sexual risk behaviors, and testing for sexually transmitted infections (STIs). One set of results suggests that using online social networks for partner seeking (compared to not using the networks for seeking partners) is associated with increased sexual risk behaviors. Supporting data suggest that (1) using online social networks to talk about safe sex is associated with an increased likelihood of having met a recent sex partner online, and (2) having online sex partners and talking to friends on online social networks about drugs and partying is associated with increased exchange sex. However, results also suggest that online social network usage is associated with increased knowledge and HIV/STI prevention among homeless youth: (1) using online social networks to talk about love and safe sex is associated with increased knowledge about HIV, (2) using the networks to talk about love is associated with decreased exchange sex, and (3) merely being a member of an online social network is associated with increased likelihood of having previously tested for STIs. Taken together, this study suggests that online social networking and the topics discussed on these networks can potentially increase and decrease sexual risk behaviors depending on how the networks are used. Developing sexual health services and interventions on online social networks could reduce sexual risk behaviors. © 2010 The Author(s).


Population pharmacokinetic and dynamic modeling is often employed to analyze data of steady-state trough serum digoxin concentrations in the course of what is frequently regarded as routine therapeutic drug monitoring (TDM). Such a monitoring protocol is extremely uninformative. It permits only the estimation of a single parameter of a 1-compartment model, such as clearance. The use of D-optimal design strategies permits much more information to be obtained, employing models having a really meaningful structure. Strategies and protocols for routine TDM policies greatly need to be improved, incorporating these principles of optimal design. Software for population pharmacokinetic modeling has been dominated by NONMEM. However, because NONMEM is a parametric method, it must assume a shape for the model parameter distributions. If the assumption is not correct, the model will be in error, and the most likely results given the raw data will not be obtained. In addition, the likelihood as computed by NONMEM is only approximate, not exact. This impairs statistical consistency and reduces statistical efficiency and the resulting precision of model parameter estimates. Other parametric methods are superior, as they provide exact likelihoods. However, they still suffer from the constraints of assuming the shape of the model parameter distributions. Nonparametric methods are more flexible. One need not make any assumptions about the shape of the parameter distributions. Nonparametric methods also provide exact likelihoods and are statistically consistent, efficient, and precise. They also permit maximally precise dosage regimens to be developed for patients using multiple model dosage design, something parametric modeling methods cannot do. Laboratory assay errors are better described by the reciprocal of the assay variance of each measurement rather than by coefficient of variation. This is easy to do and permits more precise models to be made. This also permits estimation of assay error separately from the other sources of uncertainty in the clinical environment. This is most useful scientifically. Digoxin has at least 2-compartment behavior. Its pharmacologic and clinical effects correlate not with serum digoxin concentrations but with those in the peripheral nonserum compartment. Some illustrative clinical examples are discussed. It seems that digitalis therapy, guided by TDM and our 2 compartment models based on that of Reuning et al, can convert at least some patients with atrial fibrillation and flutter to regular sinus rhythm. Investigators have often used steady-state trough concentrations only to make a 1-compartment model and have sought only to predict future steady-state trough concentrations. Much more than this can be done, and clinical care can be much improved. Further work along these lines is greatly to be desired. Copyright © 2012 by Lippincott Williams & Wilkins.


Peti-Peterdi J.,University of Southern California | Harris R.C.,Vanderbilt University
Journal of the American Society of Nephrology | Year: 2010

Macula densa cells in the distal nephron, according to the classic paradigm, are salt sensors that generate paracrine chemical signals in the juxtaglomerular apparatus to control vital kidney functions, including renal blood flow, glomerular filtration, and renin release. Renin is the rate-limiting step in the activation of the renin-angiotensin system, a key modulator of body fluid homeostasis. Here, we discuss recent advances in understanding macula densa sensing and suggest these cells, in addition to salt, also sense various chemical and metabolic signals in the tubular environment that directly trigger renin release. Copyright © 2010 by the American Society of Nephrology.


Demetriades D.,University of Southern California
International Wound Journal | Year: 2012

The management of complex abdominal problems with the 'open abdomen' (OA) technique has become a routine procedure in surgery. The number of cases treated with an OA has increased dramatically because of the popularisation of damage control for life-threatening conditions, recognition and treatment of intra-abdominal hypertension and abdominal compartment syndrome and new evidence regarding the management of severe intra-abdominal sepsis. Although OA has saved numerous lives and has addressed many problems related to the primary pathology, this technique is also associated with serious complications. New knowledge about the pathophysiology of the OA and the development of new technologies for temporary abdominal wall closure (e.g. ABThera™ Open Abdomen Negative Pressure Therapy; KCI USA Inc., San Antonio, TX) has helped improve the management and outcomes of these patients. This review will merge expert physician opinion with scientific evidence regarding the total management of the OA. © 2012 The Author. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.


Bergmann R.,University of Trier | Gil Y.,University of Southern California
Information Systems | Year: 2014

In the recent years, the use of workflows has significantly expanded from its original domain of business processes towards new areas. The increasing demand for individual and more flexible workflows asks for new methods that support domain experts to create, monitor, and adapt workflows. The emergent field of process-oriented case-based reasoning addresses this problem by proposing methods for reasoning with workflows based on experience. New workflows can be constructed by reuse of already available similar workflows from a repository. Hence, methods for the similarity assessment of workflows and for the efficient retrieval of similar workflows from a repository are of core importance. To this end, we describe a new generic model for representing workflows as semantically labeled graphs, together with a related model for knowledge intensive similarity measures. Further, new algorithms for workflow similarity computation, based on Aâ search are described. A new retrieval algorithm is introduced that goes beyond traditional sequential retrieval for graphs, interweaving similarity computation with case selection. We describe the application of this model and several experimental evaluations of the algorithms in the domain of scientific workflows and in the domain of business workflows, thereby showing its broad applicability. © 2012 Elsevier Ltd.


Bharadwaj A.,Emory University | El Sawy O.A.,University of Southern California | Pavlou P.A.,Temple University | Venkatraman N.,Boston University
MIS Quarterly: Management Information Systems | Year: 2013

Over the last three decades, the prevailing view of information technology strategy has been that it is a functional-level strategy that must be aligned with the firm's chosen business strategy. Even within this socalled alignment view, business strategy directed IT strategy. During the last decade, the business infrastructure has become digital with increased interconnections among products, processes, and services. Across many firms spanning different industries and sectors, digital technologies (viewed as combinations of information, computing, communication, and connectivity technologies) are fundamentally transforming business strategies, business processes, firm capabilities, products and services, and key interfirm relationships in extended business networks. Accordingly, we argue that the time is right to rethink the role of IT strategy, from that of a functional-level strategy-aligned but essentially always subordinate to business strategy-to one that reflects a fusion between IT strategy and business strategy. This fusion is herein termed digital business strategy. We identify four key themes to guide our thinking on digital business strategy and help provide a framework to define the next generation of insights. The four themes are (1) the scope of digital business strategy, (2) the scale of digital business strategy, (3) the speed of digital business strategy, and (4) the sources of business value creation and capture in digital business strategy. After elaborating on each of these four themes, we discuss the success metrics and potential performance implications from pursuing a digital business strategy. We also show how the papers in the special issue shed light on digital strategies and offer directions to advance insights and shape future research.


Valente T.W.,University of Southern California
Science | Year: 2012

The term "network interventions" describes the process of using social network data to accelerate behavior change or improve organizational performance. In this Review, four strategies for network interventions are described, each of which has multiple tactical alternatives. Many of these tactics can incorporate different mathematical algorithms. Consequently, researchers have many intervention choices at their disposal. Selecting the appropriate network intervention depends on the availability and character of network data, perceived characteristics of the behavior, its existing prevalence, and the social context of the program.


O'Leary D.E.,University of Southern California
Decision Support Systems | Year: 2011

Blogs provide a type of website that contains information and personal opinions of the individual authors. The purpose of this paper is to review some of the literature aimed at gathering opinion, sentiment and information from blogs. This paper also extends the previous literature in a number of directions, extending the use of knowledge from tags on blogs, finding the need for domain specific terms to capture a richer understanding of mood of a blog and finding a relationship between information in message boards and blogs. The relationship between blog chatter and sales, and blogs and public image are also examined. © 2011 Elsevier B.V. All rights reserved.


Sussman S.,University of Southern California
Evaluation and the Health Professions | Year: 2010

The investigation of the applicability of Alcoholics Anonymous/Narcotics Anonymous (AA/NA) for teens has only been a subject of empirical research investigation since the early 1990s. In the present review, the author describes teen involvement in AA/NA programming, provides an exhaustive review of the outcomes of 19 studies that used an AA/NA model as part of their formal teen substance abuse treatment programs, and provides data on the effects of AA/NA attendance on abstinence at follow-up, on which youth tend to become involved in AA/NA, and on mediation of the benefits of AA/NA participation. In addition, the author suggests the reasons for somewhat limited participation by teens in more informal, community-based 12-step meetings, and makes suggestions for maximizing participation at meetings in the community. The author concludes that AA/NA participation is a valuable modality of substance abuse treatment for teens and that much can be done to increase teen participation, though more research is needed. © SAGE Publications 2010.


Toriello A.,University of Southern California
Mathematical Programming | Year: 2014

We propose a framework of lower bounds for the asymmetric traveling salesman problem (TSP) based on approximating the dynamic programming formulation with different basis vector sets. We discuss how several well-known TSP lower bounds correspond to intuitive basis vector choices and give an economic interpretation wherein the salesman must pay tolls as he travels between cities. We then introduce an exact reformulation that generates a family of successively tighter lower bounds, all solvable in polynomial time. We show that the base member of this family yields a bound greater than or equal to the well-known Held-Karp bound, obtained by solving the linear programming relaxation of the TSP's integer programming arc-based formulation. © 2013 Springer-Verlag Berlin Heidelberg and Mathematical Optimization Society.


Spellberg B.,University of Southern California
Clinical Pharmacology and Therapeutics | Year: 2014

As a result of declining new antibacterial approvals and rising antibiotic resistance, society clearly needs new treatments for bacterial infections. Specific areas of unmet need evolve over time owing to changes in resistance patterns and treatment strategies. Our goal here is to describe and prioritize the current areas of greatest unmet need for new antibacterial development based on an understanding of the most serious treatment challenges facing patients and their providers today.


O'Connor P.G.,Yale University | Nyquist J.G.,University of Southern California | McLellan A.T.,623 South 9th Street
Annals of Internal Medicine | Year: 2011

Substance use disorders create an enormous burden of medical, behavioral, and social problems and pose a major and costly public health challenge. Despite the high prevalence of substance use and its consequences, physicians often do not recognize these conditions and, as a result, provide inadequate patient care. At the center of this failure is insufficient training for physicians about substance use disorders. To address this deficit, the Betty Ford Institute convened a meeting of experts who developed the following 5 recommendations focused on improving training in substance abuse in primary care residency programs in internal medicine and family medicine: 1) integrating substance abuse competencies into training, 2) assigning substance abuse teaching the same priority as teaching about other chronic diseases, 3) enhancing faculty development, 4) creating addiction medicine divisions or programs in academic medical centers, and 5) making substance abuse screening and management routine care in new models of primary care practice. This enhanced primary care residency training should represent a major step forward in improving patient care. © 2011 American College of Physicians.


Levine M.E.,University of Southern California
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Biological age (BA) is useful for examining differences in aging rates. Nevertheless, little consensus exists regarding optimal methods for calculating BA. The aim of this study is to compare the predictive ability of five BA algorithms. The sample included 9,389 persons, aged 30-75 years, from National Health and Nutrition Examination Survey III. During the 18-year follow-up, 1,843 deaths were counted. Each BA algorithm was compared with chronological age on the basis of predictive sensitivity and strength of association with mortality. Results found that the Klemera and Doubal method was the most reliable predictor of mortality and performed significantly better than chronological age. Furthermore, when included with chronological age in a model, Klemera and Doubal method had more robust predictive ability and caused chronological age to no longer be significantly associated with mortality. Given the potential of BA to highlight heterogeneity, the Klemera and Doubal method algorithm may be useful for studying a number of questions regarding the biology of aging. © 2012 © The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


Tustin N.,University of Southern California
Journal of Health Communication | Year: 2010

Studies of online health information seeking are beginning to address a basic question: why do people turn to the Internet? This study draws upon the Uses and Gratifications (UG) and Media System Dependency (MSD) perspectives to examine in this process the role played by satisfaction with care. The sample comprised 178 cancer listserv users, of whom 35% chose the Internet as their preferred source of health information compared with 19% who named their oncologist. Dissatisfied patients were significantly more likely to rate the Internet as a better source of information than the provider (p=.001). The level of empathy shown by the provider and the quality of time spent with the patient had a significant negative association with choosing the Internet as a preferred source of information, and a significant positive association with choosing the oncologist as an information source. The results from this study emphasize the significance of the patient-provider interaction. Dissatisfied patients' tendency to seek and trust information sources other than their physician also may have implications for compliance with treatment. Copyright © Taylor & Francis Group, LLC.


Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.


Avramis V.I.,University of Southern California
Anticancer Research | Year: 2012

This is an ambitious effort attempting to present as many aspects as possible in a review article on asparaginases (ASNase), and their use against acute lymphoblastic leukemia (ALL) and T-cell lymphomas. In the process, the modes of drug resistance are described both of the host and in the leukemia cells themselves. These modes of drug resistance, developed by the ALL cells, are an attempt to overcome the toxic insult this class of anti-leukemic drugs causes to them. It is expected that by reading this article one would obtain a better understanding of the initial events in the leukemia development, its microenvironment, and the many issues that a leukemia specialist has to deal with, especially in the treatment of refractory and relapsed patient populations. The specific issues addressed in this review deal with the importance of nutrients in tumor growth and progression of malignancies; the cytogenetics of ALL, as well as its chemotherapy, are also briefly presented. The emphasis will turn to ASNase, their mechanisms of action, the immune responses they cause in a significant percentage of the ALL patients, the significance of the up-regulation of glutamine synthetase and asparagine synthetase and the complexity of the elucidation of the mechanisms of action of ASNase. Additional details on the ASNase epitope mapping of anti- ASNase antibodies, the degradation of the protein, and the unmet needs in producing an optimal ASNase protein, will be also presented. Finally, a brief description of the toxicity, as well as the correlative factor of ALL treatment with ASNase is given.


Sohal R.S.,University of Southern California | Orr W.C.,Southern Methodist University
Free Radical Biology and Medicine | Year: 2012

The main objective of this review is to examine the role of endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the postreproductive phase of life and eventually the death of the organism. This "structural damage-based oxidative stress" hypothesis has received support from the age-associated increases in the rate of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage accrued during aging often does not match the magnitude of functional losses. Although experimental augmentation of antioxidant defenses tends to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation, and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed the "redox stress hypothesis," proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the overoxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms. © 2011 Elsevier Inc. © 2011 Elsevier Inc. All rights reserved.


Bars I.,University of Southern California
International Journal of Modern Physics A | Year: 2010

Position and momentum enter at the same level of importance in the formulation of classical or quantum mechanics. This is reflected in the invariance of Poisson brackets or quantum commutators under canonical transformations, which I regard as a global symmetry. A gauge symmetry can be defined in phase space (XM, PM) that imposes equivalence of momentum and position for every motion at every instant of the worldline. One of the consequences of this gauge symmetry is a new formulation of physics in space-time. Instead of one time there must be two, while phenomena described by one-time physics in 3+1 dimensions appear as various "shadows" of the same phenomena that occur in 4+2 dimensions with one extra space and one extra time dimensions (more generally, d+2). The 2T-physics formulation leads to a unification of 1T-physics systems not suspected before and there are new correct predictions from 2T-physics that 1T-physics is unable to make on its own systematically. Additional data related to the predictions, that provides information about the properties of the extra 1-space and extra 1-time dimensions, can be gathered by observers stuck in 3+1 dimensions. This is the probe for investigating indirectly the extra 1+1 dimensions which are neither small nor hidden. This 2T formalism that originated in 1998 has been extended in recent years from the worldline to field theory in d+2 dimensions. This includes 2T field theories that yield 1T field theories for the Standard Model and General Relativity as shadows of their counterparts in 4+2 dimensions. Problems of ghosts and causality in a 2T space-time are resolved automatically by the gauge symmetry, while a higher unification of 1T field theories is obtained. In this paper the approach will be described at an elementary worldline level, and the current status of 2T-physics will be summarized. © 2010 World Scientific Publishing Company.


Liman E.R.,University of Southern California
Handbook of Experimental Pharmacology | Year: 2014

TRPM5 is a Ca2+-activated cation channel that mediates signaling in taste and other chemosensory cells. Within taste cells, TRPM5 is the final element in a signaling cascade that starts with the activation of G protein-coupled receptors by bitter, sweet, or umami taste molecules and that requires the enzyme PLCβ2. PLCβ2 breaks down PIP2 into DAG and IP3, and the ensuing release of Ca2+ from intracellular stores activates TRPM5. Since its initial discovery in the taste system, TRPM5 has been found to be distributed in sparse chemosensory cells located throughout the digestive track, in the respiratory system, and in the olfactory system. It is also found in pancreatic islets, where it contributes toinsulin secretion. This review highlights recent work on the mechanisms of the activation of the TRPM5 channel and its regulation by voltage, phosphoinositides, temperature, and pH. The distribution of the channel in the body and its functional contribution to various sensory and nonsensory processes are discussed. © Springer-Verlag Berlin Heidelberg 2014.


Sattler F.R.,University of Southern California
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

Secretion of growth hormone (GH) and IGF-1 levels decline during advancing years-of-life. These changes (somatopause) are associated with loss of vitality, muscle mass, physical function, together with the occurrence of frailty, central adiposity, cardiovascular complications, and deterioration of mental function. For GH treatment to be considered for anti-aging, improved longevity, organ-specific function, or quality of life should be demonstrable. A limited number of controlled studies suggest that GH supplementation in older men increases lean mass by ∼2 kg with similar reductions in fat mass. There is little evidence that GH treatment improves muscle strength and performance (e.g. walking speed or ability to climb stairs) or quality of life. The GHRH agonist (tesamorelin) restores normal GH pulsatility and amplitude, selectively reduces visceral fat, intima media thickness and triglycerides, and improves cognitive function in older persons. This report critically reviews the potential for GH augmentation during aging with emphasis on men since women appear more resistant to treatment. © 2013 Published by Elsevier Ltd.


Dunton G.F.,University of Southern California
Journal of physical activity & health | Year: 2011

This study used real-time electronic surveys delivered through mobile phones, known as Ecological Momentary Assessment (EMA), to determine whether level and experience of leisure-time physical activity differ across children's physical and social contexts. Children (N = 121; ages 9 to 13 years; 52% male, 32% Hispanic/Latino) participated in 4 days (Fri.-Mon.) of EMA during nonschool time. Electronic surveys (20 total) assessed primary activity (eg, active play/sports/exercise), physical location (eg, home, outdoors), social context (eg, friends, alone), current mood (positive and negative affect), and enjoyment. Responses were time-matched to the number of steps and minutes of moderate-to-vigorous physical activity (MVPA; measured by accelerometer) in the 30 minutes before each survey. Mean steps and MVPA were greater outdoors than at home or at someone else's house (all P < .05). Steps were greater with multiple categories of company (eg, friends and family together) than with family members only or alone (all P < .05). Enjoyment was greater outdoors than at home or someone else's house (all P < .05). Negative affect was greater when alone and with family only than friends only (all P < .05). Results describing the value of outdoor and social settings could inform context-specific interventions in this age group.


Leventhal A.M.,University of Southern California
American Journal of Health Behavior | Year: 2012

Objective: To examine the relation of 2 measures of anhedonia - a specific facet of depression indicative of inability to experience pleasure - to physical activity (PA). Method: Cross-sectional correlational survey study of 157 college students (73% female, M age 19.9 years). Results: One or both measures of anhedonia were inversely associated with walking frequency, moderate-intensity PA frequency and duration, and vigorous-intensity PA frequency and duration (βs -16 to -.27, Ps < .05). Some of these associations were statistically mediated by lower PA enjoyment. Conclusions: Deficient pleasure may be an important affective mechanism underlying PA behavior. Copyright (c) PNG Publications.


Vadmal M.,University of Southern California
Cancer | Year: 2013

In the 3 decades from 1940 to 1970, the United States became the nucleus for research, diagnosis, and treatment of cancer. The discovery of anticancer drugs, and the clinical demonstration that chemotherapy and radiation can cure cancer and have the ability to prevent recurrence of cancer, were incontrovertibly the most remarkable groundbreaking events. Consequently, the trend of less surgery and more multimodality therapy began. The introduction of radioautography, mammography, ultrasonography, computed tomography, Papanicolaou smear, and other novel laboratory tests furthered early detection of cancer and refined accurate diagnosis. The unequivocal linking of lung cancer to cigarette smoking made medical history. The delineation of the potential role of oncogenes adduced new thoughts about oncogenesis and cancer prevention, and pathologists finalized the classification and nosology of tumors. Finally, it is worth noting that although more advances were made in the detection, diagnosis, and treatment of cancers than any other period in history, the overall mortality rate of patients with cancer remained high and unchanged. Cancer 2013;119:4058-4082. © 2013 American Cancer Society. Major events and discoveries in cancer research, diagnosis, and treatment that took place between 1940 and 1970 are reviewed. © 2013 American Cancer Society.


Young G.,University of Southern California
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

For the past 5 decades, the care for hemophilia patients has improved significantly to the point that a newborn with hemophilia living in a developed nation can expect to have a normal lifespan and a high quality of life. Despite this, there are several new challenges that the hemophilia community will face in the coming years. First, the hemophilia community will soon be challenged with adopting a variety of new agents into clinical practice. Second, the normalization of patients' lives as a result of improved treatment has led to new problem areas, including obese/overweight hemophiliacs and osteoporosis. In addition, although mortality rates are similar to those of the healthy population, morbidities such as hemophilic arthropathy still occur. Third, the cost of care continues to rise, both due to the development of expensive new therapies and to the costs of managing problems such as obesity and osteoporosis. Finally, most patients in the world with hemophilia receive little to no care and although this is an enormous challenge, it must be confronted. This review discusses some new challenges facing developing nations and their care for hemophilia patients. In summary, in hemophilia in the coming few years, several new challenges will need to be confronted.


Borchert M.,University of Southern California
Journal of Neuro-Ophthalmology | Year: 2012

BACKGROUND: Optic nerve hypoplasia (ONH) has been described as an increasingly prevalent cause of congenital blindness. Its association with hypopituitarism and absent septum pellucidum has been recognized for more than 40 years as "septo-optic dysplasia" or "de Morsier syndrome." More recent studies have suggested that these associations are independent of one another. This review was designed to assess the historical and recent evidence for associations of neuroradiologic, endocrinologic, and developmental problems in patients with ONH. EVIDENCE ACQUISITION: Historical and contemporary literature review. RESULTS: The medical literature does not support the notion that Georges de Morsier ever described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt. Hypopituitarism and other more recently identified associations with ONH, such as developmental delay, hypothalamic dysfunction, and autism, are independent of septum pellucidum development. Other common neuroradiographic associations, such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia, may have prognostic significance. CONCLUSIONS: Children with ONH need to be monitored for many systemic, developmental, and even life-threatening problems independent of the status of the septum pellucidum. "Septo-optic dysplasia" and "de Morsier syndrome" are historically inaccurate and clinically misleading terms that should be abandoned. Copyright © North American Neuro-Ophthalmology Society.


Dong H.,Brown University | Kim D.,University of Southern California
Archive for Rational Mechanics and Analysis | Year: 2010

The solvability in Sobolev spaces is proved for divergence form second order elliptic equations in the whole space, a half space, and a bounded Lipschitz domain. For equations in the whole space or a half space, the leading coefficients aij are assumed to be only measurable in one direction and have locally small BMO semi-norms in the other directions. For equations in a bounded domain, additionally we assume that aij have small BMO semi-norms in a neighborhood of the boundary of the domain. We give a unified approach of both the Dirichlet boundary problem and the conormal derivative problem. We also investigate elliptic equations in Sobolev spaces with mixed norms under the same assumptions on the coefficients. © Springer-Verlag (2009).


Taylor C.R.,University of Southern California
Cell and Tissue Research | Year: 2015

Companion diagnostics, tests that purport to classify patients into “responders” and “non-responders” for a specified targeted therapy, demand methods that quantify the actual amount of the corresponding target molecule in tumors from these patients. Various methods are employed depending upon the nature of the target. Many of the candidate therapeutic agents target the abnormal expression of a protein, the detection of which lends itself to an immunohistochemistry (IHC) approach. This review focuses on IHC with formalin-fixed paraffin-embedded (FFPE) tissues for purely pragmatic reasons; first, the morphologic information pertaining to the tumor is of value and should not be discarded as in extraction type assays; second, FFPE tissues are mostly what we have to hand at the time that the diagnostic question is posed. During the four decades of employment of IHC involving the production of a variety of special stains used in the diagnosis or classification of tumors, we have acquired some bad habits, essentially when judging the IHC result via the perception of a “good” stain that “pleases the eye” of the user pathologist, and nothing more. This review takes, as its basic premise, the notion that IHC can be upgraded from its use as a qualitative special staining method to an accurate and reliable quantitative “tissue-based immunologic assay”. If accomplished, this enhanced IHC assay would serve accurately to quantify proteins in tissue sections, analogous to the use of the ELISA (enzyme-linked immunosorbent assay) method in the clinical laboratory. The necessary steps for converting IHC to a tissue-based ELISA-like immunoassay of immediate practical use are reviewed with constructive suggestions for steps that can be (must be) taken to achieve the practical reality of quantitative in situ proteomics. © 2015, Springer-Verlag Berlin Heidelberg.


Suh M.,University of Southern California
Journal of High Energy Physics | Year: 2011

We explicitly truncate N = 8 gauged supergravity in five dimensions to its SU(3)-invariant sector with dilaton and axion fields. We show that this truncation has a solution which is identical to the super Janus constructed in N = 2 gauged supergravity in five dimensions. Then we lift the solution of the SU(3)-invariant truncation to type IIB supergravity by employing the consistent truncation ansatz. We show that the lifted solution falls into a special case of the supersymmetric Janus solutions constructed in type IIB supergravity. Additionally, we also prove that the lifted solution provides a particular example of the consistent truncations of type IIB supergravity on Sasaki-Einstein manifolds. © SISSA 2011.


DeMeester S.R.,University of Southern California
Journal of Gastrointestinal Surgery | Year: 2010

Introduction: Adenocarcinoma of the esophagus is the fastest increasing cancer in the USA, and an increasing number of patients are identified with early-stage disease. The evaluation and treatment of these superficial cancers differs from local and regionally advanced lesions. Methods: This paper is a review of the current methods to diagnose, stage, and treat superficial esophageal adenocarcinoma. Results: Intramucosal adenocarcinoma can be effectively treated with endoscopic resection techniques and with less morbid surgical options including a vagal-sparing esophagectomy. However, submucosal lesions are associated with a significant risk for lymph node metastases and are best treated with esophagectomy and lymphadenectomy. Discussion: There has been a major shift in the treatment for Barrett's high-grade dysplasia and superficial esophageal adenocarcinoma in the past 10 years. New therapies minimize the morbidity and mortality of traditional forms of esophagectomy and in some cases allow esophageal preservation. Individualization of therapy will allow maximization of successful outcome and quality of life with minimization of complications and recurrence of Barrett's or cancer. © 2009 The Society for Surgery of the Alimentary Tract.


Stearns K.M.,University of Southern California | Pollard C.D.,Oregon State University
American Journal of Sports Medicine | Year: 2013

Background: Athletes who have undergone anterior cruciate ligament reconstruction (ACLR) have a high risk of reinjury upon the return to sports participation. While the mechanisms behind this increased risk of reinjury are unknown, it has been suggested that altered knee biomechanics during sports-specific activities may be a contributing factor. Purpose/Hypothesis: To compare frontal plane knee joint angles and moments during a sidestep cutting maneuver in female soccer athletes who have undergone ACLR with those in athletes with no history of knee injury. It was hypothesized that athletes with a history of ACLR would exhibit increased knee abduction angles and knee adductor moments compared with those with no history of injury. Study Design: Controlled laboratory study. Methods: Twelve female soccer players with a history of ACLR served as the experimental group, and 12 female soccer players with no history of knee injury constituted the control group. Three-dimensional kinematics and ground-reaction forces were collected while each participant performed a sidestep cutting maneuver. Variables of interest included the knee abduction angle and knee adductor moment during the early deceleration phase of the cutting maneuver. Independent-samples t tests were used to evaluate differences between groups (P ≤ .05). Results: Participants in the ACLR group exhibited increased average knee abduction angles (ACLR: 3.8≤ vs control: 1.8≤; P = .03) and peak knee adductor moments (ACLR: 1.33 N·m/kg vs control: 0.80 N·m/kg; P = .004) compared with the control group. Conclusion: Female soccer players who have undergone ACLR and returned to sports participation exhibited increased knee abduction angles and knee adductor moments during the early deceleration phase of cutting compared with their healthy counterparts with no history of knee injury. Clinical Relevance: Even though athletes are able to return to sport after ACLR, they are at an increased risk for reinjury. It may be the case that the increased frontal plane knee angles and moments exhibited by these athletes after ACLR could be contributing to this risk for reinjury. Therefore, it is important that rehabilitation programs after ACLR include the restoration of frontal plane knee mechanics. © 2013 The Author(s).


Malamed S.F.,University of Southern California
Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995) | Year: 2013

The pH of lidocaine with epinephrine in dental cartridges ranges between 2.9 and 4.4. In this pH range, less than 0.1% of the anesthetic is in the de-ionized or "active" form. The acidity of the anesthetic may delay onset and contribute to injection pain. The study compared anesthetic latency and injection pain for alkalinized versus non-alkalinized anesthetic in inferior alveolar nerve blocks (IANBs). The study buffered the anesthetic directly in the cartridges using a mixing pen device. The study included 20 participants, each receiving one control and one test IANB injection. The control solution was non-alkalinized 2% lidocaine/epinephrine 1:100,000 at pH 3.85. The test solution was 2% lidocaine/ epinephrine 1:100,000 alkalinized to pH 7.31. Latency was measured using endodontic ice confirmed with an electric pulp tester (EPT), and injection pain was measured using a visual analog scale (VAS). ONSET TIME: With the alkalinized anesthetic, 71% of participants achieved pulpal analgesia in 2 minutes or less. With non-alkalinized anesthetic, 12% achieved pulpal analgesia in 2 minutes or less (P = 0.001). The average time to pulpal analgesia for the non-alkalinized anesthetic was 6:37 (range 0:55 to 13:25). Average time to pulpal analgesia for alkalinized anesthetic was 1:51 (range 0:11 to 6:10) (P = 0.001). INJECTION PAIN RESULTS: 72% of the participants rated the alkalinized injection as more comfortable, 11% rated the non-alkalinized injection as more comfortable, and 17% reported no preference (P = 0.013). Forty-four percent of the patients receiving alkalinized anesthetic rated the injection pain as zero ("no pain") on a 100-mm VAS, compared to 6% of the patients who received non-alkalinized anesthetic (P = 0.056). Alkalinizing lidocaine with epinephrine toward physiologic pH immediately before injection significantly reduces anesthetic onset time and increases the comfort of the injection. Clinicians can begin procedures more quickly and give a more comfortable injection by alkalinizing their lidocaine/epinephrine immediately before delivering the injection.


Duncan J.W.,University of Southern California | Bailey R.A.,11 West College Street
European Spine Journal | Year: 2013

Purpose: To investigate if instrumentation (unilateral vs. bilateral fixation) has an effect on the rate of fusion cage migration. Methods: This clinical study of transforaminal lumbar interbody fusion involved a prospective group of 116 patients who were randomly assigned to either unilateral (n = 57) or bilateral (n = 59) fixation. Fourteen were lost to follow-up (11 from the unilateral group and 3 from the bilateral group). Results: The unilateral fixation group consisted of 20 male and 26 female patients. In the unilateral group, the mean age was 53.5 years (range, 18-77), and the preoperative diagnosis consisted of degenerative disc disease, with or without herniated disc (n = 44), and degenerative spondylolisthesis with spinal stenosis (n = 2). The bilateral fixation group consisted of 20 male and 36 female patients. In the bilateral group, the mean age was 55.7 years (range, 26-82), and the preoperative diagnosis consisted of degenerative disc disease, with or without herniated disc (n = 40), and degenerative spondylolisthesis with spinal stenosis (n = 16). A total of 17 cases of cage migration were found; of these, 11 were from the unilateral group and 6 from the bilateral group, resulting in rates of cage migration of 23 and 11 % (p = 0.03), respectively. In regard to migration cases, 5 were male and 12 were female. Ages ranged from 27 to 79 years (mean age, 55 years). Conclusion: We conclude that unilateral fixation is not stable enough to prevent fusion cage migration in some patients who undergo TLIF. © 2012 Springer-Verlag.


Gruntman M.,University of Southern California
Journal of Geophysical Research: Space Physics | Year: 2013

Relative motion of the Sun with respect to the surrounding local interstellar medium results in entering of interstellar helium atoms into the heliosphere. Current models of helium flowing into the solar system do not include elastic collisions of atoms with solar wind ions. It was predicted in 1986, without quantitative elaboration, that such collisions would enhance wings of directional distributions of helium atom fluxes. This paper focuses on a theoretical treatment of elastic collisions of interstellar He atoms with the solar wind protons resulting in increased wing intensities, called the helium flux halo in contradistinction to the flux core. We concentrate on directional distributions of He atom intensities at 1 AU from the Sun for observers at rest and moving with the Earth and confirm the formation of the flux halo. We show that the collision-produced halo would often dominate He atom intensities at angles larger than 30°-35° from the maximum intensity direction in the flux core. A comparison with direct measurements of interstellar helium atom fluxes is beyond the scope of this paper. Key Points formation of interstellar helium atom flux halocollisional heating of interstellar helium in the heliosphere ©2013. American Geophysical Union. All Rights Reserved.


Literat I.,University of Southern California
Learning, Media and Technology | Year: 2013

Participatory mapping attempts to engage youth in the generation of personalized maps, as a way to both harness the value of individual knowledge about geographic space, and to concurrently empower the research participants by inviting them to take an active stake in the representation and explication of their spatial environment. Engagement in the mapping exercise facilitates a nuanced process of reflection - often unrealizable through purely textual methods - and can stimulate youth empowerment by seeding critical conversations around personal safety, mobility and technologies of spatial representation. Findings from a study that implemented participatory mapping in the context of an after-school program for urban high school students are used to demonstrate the potential of this research strategy as a participatory pedagogical intervention, and to extract methodological recommendations for its effective implementation in urban educational settings. © 2013 Copyright Taylor and Francis Group, LLC.


Rison R.A.,University of Southern California
Journal of Medical Case Reports | Year: 2013

Case reports are a time-honored, important, integral, and accepted part of the medical literature. Both the Journal of Medical Case Reports and the Case Report section of BioMed Central Research Notes are committed to case report publication, and each have different criteria. Journal of Medical Case Reports was the world's first international, PubMed-listed medical journal devoted to publishing case reports from all clinical disciplines and was launched in 2007. The Case Report section of BioMed Central Research Notes was created and began publishing case reports in 2012. Between the two of them, thousands of peer-reviewed case reports have now been published with a worldwide audience. Authors now also have Cases Database, a continually updated, freely accessible database of thousands of medical case reports from multiple publishers. This informal editorial outlines the process and mechanics of how and when to write a case report, and provides a brief look into the editorial process behind each of these complementary journals along with the author's anecdotes in the hope of inspiring all authors (both novice and experienced) to write and continue writing case reports of all specialties. Useful hyperlinks are embedded throughout for easy and quick reference to style guidelines for both journals. © 2013 Rison; licensee BioMed Central Ltd.


Kashani A.H.,University of Southern California
Retina | Year: 2015

PURPOSE:: To noninvasively evaluate the retinal microvasculature in human subjects with retinal venous occlusions using optical coherence tomography angiography and assess potential clinical applications. METHODS:: This was a prospective, observational study of adult human subjects with clinical and imaging findings demonstrating retinal venous occlusion. Subjects underwent complete ophthalmic examination and fluorescein angiography as appropriate for their standard of care. Optical coherence tomography angiography was performed on a prototype spectral domain-OCTA system in 3 mm × 3 mm and 6 mm × 6 mm regions centered on the fovea and parafoveal areas. Retinal vasculature was assessed within three horizontal slabs consisting of the superficial, middle, and deep retina. The vasculature within each slab was reconstructed using intensity contrast-based algorithms and visualized as en-face images. Optical coherence tomography angiograms were manually segmented to verify the accuracy of the automated segmentation algorithms. RESULTS:: Optical coherence tomography angiography was able to demonstrate almost all of the clinically relevant findings in 25 subjects with acute and chronic retinal venous occlusion. These findings were consistent with clinical, anatomic, and fluorescein angiographic findings including areas of impaired vascular perfusion, retinal atrophy, vascular dilation, shunt vessels, and some forms of intraretinal edema. CONCLUSION:: Optical coherence tomography angiography is an investigational method that generates high-resolution, noninvasive angiograms that qualitatively illustrate most of clinically relevant findings in retinal venous occlusion. Optical coherence tomography angiography corresponds well with fluorescein angiograms and in many cases provides more detailed anatomic and blood flow information. Optical coherence tomography angiography, in conjunction with standard spectral domain-OCT, is at least equally as effective as fluorescein angiography for evaluation and management of the macular complications of retinal venous occlusions. © 2015 by Ophthalmic Communications Society, Inc.


Stohl W.,University of Southern California
Nature Reviews Rheumatology | Year: 2013

With the approval by the FDA in 2011 of a biologic agent (namely belimumab) for the treatment of systemic lupus erythematosus (SLE), optimism abounds that additional biologic (and nonbiologic) agents will be similarly endorsed. Given the numerous immune-based abnormalities associated with SLE, the potential therapeutic targets for biologic agents and the candidate biologic approaches are also numerous. These approaches include: biologic agents that promote B-cell depletion, B-cell inactivation, or the generation of regulatory B cells; biologic agents that induce T-cell tolerance, block T-cell activation and differentiation, or alter T-cell trafficking; biologic agents that target the B-cell activating factor (BAFF) axis, type I interferons, IL-6 and its receptor, or TNF; and the adoptive transfer of ex vivo-generated regulatory T cells. Owing to the great heterogeneity inherent to SLE, no single approach should be expected to be effective in all patients. As our understanding of the pathogenic mechanisms of SLE continues to expand, additional therapeutic targets and approaches will undoubtedly be identified and should be fully exploited. © 2013 Macmillan Publishers Limited. All rights reserved.


Frohlich J.,University of California at Los Angeles | Van Horn J.D.,University of Southern California
Journal of Psychopharmacology | Year: 2014

The observation that antagonists of the N-methyl-D-aspartate receptor (NMDAR), such as phencyclidine (PCP) and ketamine, transiently induce symptoms of acute schizophrenia had led to a paradigm shift from dopaminergic to glutamatergic dysfunction in pharmacological models of schizophrenia. The glutamate hypothesis can explain negative and cognitive symptoms of schizophrenia better than the dopamine hypothesis, and has the potential to explain dopamine dysfunction itself. The pharmacological and psychomimetic effects of ketamine, which is safer for human subjects than phencyclidine, are herein reviewed. Ketamine binds to a variety of receptors, but principally acts at the NMDAR, and convergent genetic and molecular evidence point to NMDAR hypofunction in schizophrenia. Furthermore, NMDAR hypofunction can explain connectional and oscillatory abnormalities in schizophrenia in terms of both weakened excitation of inhibitory γ-aminobutyric acidergic (GABAergic) interneurons that synchronize cortical networks and disinhibition of principal cells. Individuals with prenatal NMDAR aberrations might experience the onset of schizophrenia towards the completion of synaptic pruning in adolescence, when network connectivity drops below a critical value. We conclude that ketamine challenge is useful for studying the positive, negative, and cognitive symptoms, dopaminergic and GABAergic dysfunction, age of onset, functional dysconnectivity, and abnormal cortical oscillations observed in acute schizophrenia. © 2013 The Author(s).


For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab, is a monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). Although belimumab has demonstrated a very favorable safety profile, many SLE patients have failed to clinically improve from belimumab therapy. Three additional BLyS antagonists (atacicept, blisibimod, tabalumab) are currently undergoing clinical testing. These antagonists subtly differ from belimumab in their biologic targets, and each is administered through a route (subcutaneous) that differs from the route through which belimumab is currently delivered (intravenous). Whether these differences will have meaningful consequences for efficacy and safety remains to be determined. © Springer Science+Business Media, LLC 2012.


Platt J.P.,University of Southern California
Journal of Structural Geology | Year: 2015

Ductile shear zones commonly contain distinctive bands of high strain rock characterized by intimately mixed fine-grained two-phase or polyphase material. These ultramylonite bands are weaker than the surrounding material, and may play a critical role in strain localization. How such zones develop, how the phases become evenly dispersed, the bulk rheology, and the controls on grain size, are all unclear. The following generic scenario may resolve some of these questions.1) Dislocation creep and dynamic recrystallization cause grain-size reduction: commonly, the recrystallized grain sizes of the two phases differ.2) Grain size reduction causes a switch to grain-boundary diffusion creep, which requires grain-boundary sliding. Diffusion allows one phase to fill spaces that open between grains of the other: this will happen most rapidly in the finer-grained phase. The grain size of the resulting mixture is therefore controlled by that of the finer-grained phase. This leads to mixing and dispersion of the two phases, producing a fine-grained, evenly dispersed two-phase aggregate.3) The bulk rheology will be controlled by grain-boundary diffusion creep of the two phases, with the grain size controlled by the finer-grained phase. Bulk flow laws can be developed for quartz-feldspar and olivine-orthopyroxene ultramylonites based on these concepts, using appropriate mixing laws. © 2015 Elsevier Ltd.


Gerczuk P.Z.,Heart Institute | Kloner R.A.,Heart Institute | Kloner R.A.,University of Southern California
Journal of the American College of Cardiology | Year: 2012

Acute myocardial infarction (AMI) with subsequent left ventricular dysfunction and heart failure continues to be a major cause of morbidity and mortality in the Western world. Rapid advances in the treatment of AMI, mainly through timely reperfusion, have substantially improved outcomes in patients presenting with acute coronary syndrome and particularly ST-segment elevation myocardial infarction. A vast amount of research, both translational and clinical, has been published on various pharmacological and interventional techniques to prevent myocardial cell death during the time of ischemia and subsequent reperfusion. Several methods of cardioprotection have shown the ability to limit myocardial infarction size in clinical trials. Examples of interventional techniques that have proven beneficial are ischemic post-conditioning and remote ischemic per-conditioning, both of which can reduce infarction size. Lowering core body temperature with cold saline infusion and cooling catheters have also been shown to be effective in certain circumstances. The most promising pharmaceutical cardioprotective agents at this time appear to be adenosine, atrial natriuretic peptide, and cyclosporine, with other potentially effective medications in the pipeline. Additional pre-clinical and clinical research is needed to further investigate newer cardioprotective strategies to continue the current trend of improving outcomes following AMI. © 2012 American College of Cardiology Foundation.


Platt J.P.,University of Southern California
International Geology Review | Year: 2015

Block-in-matrix melanges at San Simeon have been variously interpreted as deformed olistostromes or as subduction-channel flow melanges. Detailed examination shows that seven types can be distinguished, with transitions among them. All contain exotic clasts of greenstone, chert, and more rarely blueschist, in addition to greywacke; the same materials also occur as blocks metres to tens of metres in diameter immersed in melange. The seven types are (1) bedded conglomerate, (2) structureless conglomerate, (3) mud-matrix conglomerate, (4) sandy block melange, (5) broken formation, (6) mud-matrix melange without deformational fabric, and (7) sheared melange. Types (1)-(3) are clearly sedimentary in origin. Types (4) and (5) were formed from unconsolidated sediment, most likely by down-slope sliding, and transitional types suggest that the mud-matrix melange (6) formed in the same way. Sheared melange (7) was formed by low-temperature post-consolidational deformation of all other types, which produced shear bands and a crude scaly fabric. Kinematic indicators of shear direction are rare, but assuming the fabric and shear bands are coeval, the shear direction and sense can be determined from the angular relationship between the two planar fabrics. Most shear planes are gently dipping, with normal-sense displacements of a few centimetres to tens of centimetres. Shear directions are highly variable, with the highest concentrations between WNW and S. This suggests that the main phase of shearing took place during a phase of approximately vertical shortening and horizontal extension, rather than during accretion. Post-accretionary dextral shearing on NNW-trending vertical planes, and sinistral shear on a variety of trends, are likely related to Neogene transform tectonics. The simplest interpretation of these relationships is that the disrupted character of the melanges formed primarily by sliding down the trench inner slope of unconsolidated sediment, including clasts and blocks of previously accreted and exhumed greenstone, chert, and blueschist. The deformational fabric is largely unrelated to the disruption, and was formed during late-stage extension in the accretionary wedge. © 2014 © 2014 Taylor & Francis.


Bondareff W.,University of Southern California
Journal of Alzheimer's Disease | Year: 2013

Alzheimer's disease is a neurodegenerative disease in which aging is not only a major risk factor but a major determinant of onset, course, and pathogenesis. The synthesis of amyloid-β (Aβ) peptides by neurons and their excretion into the extracellular space (ECS) is a core feature of AD that begins more than two decades before the onset of clinical symptoms. The ECS resembles a syncytium with the appearance in electron micrographs of continuous channels and lakes separating the outer membranes of the neurons, neuroglia, and vascular elements embedded in it. It consists primarily of a proteoglycan matrix through which circulates an interstitial fluid, derived in part from cerebrospinal fluid (CSF). The process by which Aβ accumulates in the ECS includes decreased production of CSF, matrix proteoglycans, and ECS volume, all of which become more severe with advancing age and lead to an age-related increase in the Aβ pool. Although the relationship between Aβ and the appearance of cognitive symptoms is uncertain, available data support a strong relationship between the toxicity of Aβ for neurons and the total Aβ burden, including the soluble and fibrillar Aβ, the Aβ42/ Aβ40 ratio, and Aβ-proteoglycan reactivity. Proteoglycans have been shown to foster the formation of neurotoxic fibrillar Aβ42 and neuritic plaques that enhance neuronal and synaptic damage and eventual loss culminating in the onset and progression of dementia. As this process depends upon age-related events, it suggests that the successful control of AD lies in finding effective means of prevention. © 2013 IOS Press and the authors. All rights reserved.


DeLeve L.D.,University of Southern California
Journal of Clinical Investigation | Year: 2013

Liver sinusoidal endothelial cells (LSECs) have long been noted to contribute to liver regeneration after liver injury. In normal liver, the major cellular source of HGF is the hepatic stellate cell, but after liver injury, HGF expression has been thought to increase markedly in proliferating LSECs. However, emerging data suggest that even after injury, LSEC expression of HGF does not increase greatly. In contrast, bone marrow progenitor cells of LSECs (BM SPCs), which are rich in HGF, are recruited to the liver after injury. This Review examines liver regeneration from the perspective that BM SPCs that have been recruited to the liver, rather than mature LSECs, drive liver regeneration.


Unger J.B.,University of Southern California
Substance Use and Misuse | Year: 2012

This paper discusses the limitations of previous research on race, ethnicity, culture, and substance use. The study offers the following recommendations for future research in this area: (1) move beyond simple comparisons of mutually exclusive groups, (2) focus on the meaning of an ethnic label to the individual, (3) consider the complex interactions between an individual's cultural identity and the cultural context, (4) understand and acknowledge the researcher's inherent biases, and (5) translate research findings into practice and policy change. © 2012 Informa Healthcare USA, Inc.


Kahn M.,University of Southern California
Future Medicinal Chemistry | Year: 2011

The decision for a stem cell to undergo a symmetric versus an asymmetric differentiation is probably the most critical cellular decision process in adults, as it probably underlies a large array of diseases, is associated with a decrease in tissue maintenance/homeostasis and the ability to repair properly, may mediate pathological processes such as cancer, fibrosis and neurodegeneration, and may be the underlying problem associated in general with aging. Interestingly and importantly, the decision to divide asymmetrically or symmetrically may be the major fundamental intrinsic difference between normal somatic stem and cancer stem cells. Based upon work done primarily in our laboratory over the past 10 years (both published and unpublished data), the article provides perspective on the critical importance of symmetric versus asymmetric divisions and the role of differential usage of the highly homologous coactivators Creb-binding protein (CBP) or p300 in the Wnt/catenin signaling cascade in stem cells and how they can be pharmacologically manipulated. © 2011 Future Science Ltd.


Saquib N.,Brac University | Hossain E.,University of Manitoba | Kim D.,University of Southern California
IEEE Wireless Communications | Year: 2013

Improvement of cell coverage and network capacity are two major challenges for the evolving 4G cellular wireless communication networks such as LTE-Advanced networks. In this context, hierarchical layering of cells with macro base stations coexisting with low-power and shortrange base stations (corresponding to picocells or femtocells) in a service area is considered to be an efficient solution to enhance the spectralefficiency of the network per unit area. Also, such a hierarchical cell deployment, which is referred to as a heterogeneous network, or Het-Net, provides significant improvement in the coverage of indoor and cell edge users and ensures better QoS to the users. Interference mitigation between different layers is one of the key issues that needs to be resolved for successful deployment of HetNets. To this end, fast frequency response, FFR, is considered to be an efficient intercell interference coordination technique for OFDMA-based HetNets. This article focuses on evaluating three state-of-the-art FFR deployment schemes: strict FFR, soft FFR, and FFR-3 schemes for OFDMA-based two-tier HetNets comprising macrocells overlaid with femtocells. Also, a variation of the FFR-3 scheme, which is referred to as the optimal static FFR (OSFFR) scheme, is proposed. A broad comparison among all these FFR schemes is performed by using Monte Carlo simulations considering performance metrics such as outage probability, average network sum rate, and spectral efficiency. Simulation results show that, the average gains in spectral efficiency (b/s/Hz) of the network are significantly higher for the proposed scheme when compared to the strict FFR, soft FFR, and FFR-3 schemes. © 2002-2012 IEEE.


Ralph P.,University of California at Davis | Ralph P.,University of Southern California | Coop G.,University of California at Davis
PLoS Biology | Year: 2013

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (in the Population Reference Sample [POPRES] dataset) to conduct one of the first surveys of recent genealogical ancestry over the past 3,000 years at a continental scale. We detected 1.9 million shared long genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 2-12 genetic common ancestors from the last 1,500 years, and upwards of 100 genetic ancestors from the previous 1,000 years. These numbers drop off exponentially with geographic distance, but since these genetic ancestors are a tiny fraction of common genealogical ancestors, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1,000 years. There is also substantial regional variation in the number of shared genetic ancestors. For example, there are especially high numbers of common ancestors shared between many eastern populations that date roughly to the migration period (which includes the Slavic and Hunnic expansions into that region). Some of the lowest levels of common ancestry are seen in the Italian and Iberian peninsulas, which may indicate different effects of historical population expansions in these areas and/or more stably structured populations. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world. © 2013 Ralph, Coop.


Gross G.G.,University of Southern California
Nature Methods | Year: 2016

Although neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Laine L.,University of Southern California | Hennekens C.,Florida Atlantic University
American Journal of Gastroenterology | Year: 2010

Current consensus recommendations state that patients prescribed clopidogrel plus aspirin should receive a proton pump inhibitor (PPI) to reduce gastrointestinal bleeding. Clopidogrel is converted to its active metabolite by cytochrome P450 (CYP) enzymes. Clopidogrel users with decreased CYP2C19 function have less inhibition of platelet aggregation and increased cardiovascular (CV) events. As PPI metabolism also involves CYP2C19, it was hypothesized that competition by PPIs might interfere with clopidogrel's action. Omeprazole, but not other PPIs, worsens surrogate markers of clopidogrel efficacy. Some (but not all) observational studies show that clopidogrel users prescribed PPIs have increased risks of CV events (hazard/odds ratios1.25-1.5). When effect sizes are small to moderate (relative risks1.5-2.0), however, it is only possible to conclude whether statistical associations are valid in randomized trials. A randomized trial of omeprazole vs. placebo in clopidogrel users showed no difference in CV events (hazard ratio1.02,0.70-1.51). Thus, current evidence does not justify a conclusion that PPIs are associated with CV events among clopidogrel users, let alone a judgment of causality. Nonetheless, positive results from some observational studies and biological plausibility have led some health-care providers to accept that PPIs reduce clopidogrel's efficacy. The US Food and Drug Administration (FDA) recommends that concomitant use of drugs that inhibit CYP2C19 (e.g., omeprazole) should be discouraged. As the presence of PPIs and clopidogrel in plasma is short lived, separation by 12-20 h should in theory prevent competitive inhibition of CYP metabolism and minimize any potential, though unproven, clinical interaction. PPI may be given before breakfast and clopidogrel at bedtime, or PPI may be taken before dinner and clopidogrel at lunchtime. © 2010 by the American College of Gastroenterology.


Tsai L.-C.,Northwestern University | Powers C.M.,University of Southern California
American Journal of Sports Medicine | Year: 2013

Background: Those who have undergone anterior cruciate ligament reconstruction (ACLR) have been shown to exhibit increased muscle co-contraction, decreased knee flexion, and elevated tibiofemoral compressive forces. Elevated tibiofemoral compressive forces may be associated with the high risk of developing knee osteoarthritis in this population. Purpose: To examine whether muscle co-contraction and tibiofemoral compressive forces in women after undergoing ACLR can be reduced through the use of a landing strategy that emphasizes greater hip and knee flexion. Study Design: Controlled laboratory study. Methods: Ten female recreational athletes who had previously undergone ACLR participated in this study. Participants performed a single-legged drop-land task before and after a training session that encouraged them to use greater hip and knee flexion during landing. Peak tibiofemoral compressive forces before and after training were estimated using an electromyography (EMG)driven knee model that incorporated joint kinematics, EMG, and subject-specific muscle volumes and patellar tendon orientation estimated from magnetic resonance imaging. A co-contraction index (CCI) was calculated to quantify the level of co-contraction between knee flexor and extensor muscles. Results: After training, peak hip and knee flexion as well as hip and knee flexion excursions increased significantly. Additionally, participants demonstrated a significant decrease after training in the areas of muscle co-contraction (CCI [mean ± SD], 0.28 ± 0.10 vs 0.18 ± 0.05; P<.001) and peak tibiofemoral compressive force (97.3 ± 8.0 vs 91.3 ± 10.2 Nkg1; P = .044). Conclusion: Increased muscle co-contraction as well as elevated tibiofemoral compressive loads observed in individuals following ACLR can be reduced by using a landing strategy that encourages greater hip and knee flexion. Clinical Relevance: The findings of the current study provide useful information for the growth of rehabilitation and/or intervention programs aimed to decrease knee joint loading to prevent or delay the development of knee osteoarthritis in those who have undergone ACLR. © 2012 The Author(s).


Hilbert M.,University of Southern California
Telecommunications Policy | Year: 2011

Based on the theory of the diffusion of innovations through social networks, the article discusses the main approaches researchers have taken to conceptualize the digital divide. The result is a common framework that addresses the questions of who (e.g. divide between individuals, countries, etc.), with which kinds of characteristics (e.g. income, geography, age, etc.), connects how (mere access or effective adoption), to what (e.g. phones, Internet, digital TV, etc.). Different constellations in these four variables lead to a combinatorial array of choices to define the digital divide. This vast collection of theoretically justifiable definitions is contrasted with the question of how the digital divide is defined in practice by policy makers. The cases of the United States, South Korea, and Chile are used to show that many diverse actors with dissimilar goals are involved in confronting the digital divide. Each of them takes a different outlook on the challenge. This leads to the question if this heterogeneity is harmful and if countries that count with a coherent national strategy and common outlook on digital development do better than others. It is shown that the effect of a coherent vision is secondary to tailor-made sector-specific efforts. On the contrary, a one-size-fits-all outlook on a multifaceted challenge might rather be harmful. This leads to the conclusion that it is neither theoretically feasible, nor empirically justifiable to aim for one single definition of the digital divide. The digital divide is best defined in terms of a desired impact. Since those are diverse, so are the definitions of the challenge. The best that can be done is to come up with a comprehensive theoretical framework that allows for the systematic classification of different definitions, such as the one presented in this article. © 2011 Elsevier Ltd. All rights reserved.


Finch C.E.,University of Southern California
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Humans have evolved much longer lifespans than the great apes, which rarely exceed 50 years. Since 1800, lifespans have doubled again, largely due to improvements in environment, food, and medicine that minimized mortality at earlier ages. Infections cause most mortality in wild chimpanzees and in traditional forager-farmers with limited access to modern medicine. Although we know little of the diseases of aging under premodern conditions, in captivity, chimpanzees present a lower incidence of cancer, ischemic heart disease, and neurodegeneration than current human populations. These major differences in pathology of aging are discussed in terms of genes that mediate infection, inflammation, and nutrition. Apolipoprotein E alleles are proposed as a prototype of pleiotropic genes, which influence immune responses, arterial and Alzheimer's disease, and brain development.


Ouzounian J.G.,University of Southern California
Seminars in Perinatology | Year: 2014

Neonatal brachial plexus palsy (NBPP) is an unpredictable complication of childbirth. Historic risk factors for the occurrence of NBPP have included shoulder dystocia, fetal macrosomia, labor abnormalities, operative vaginal delivery, and prior NBPP. However, whether studied alone or in combination, these risk factors have not been shown to be reliable predictors. The majority of NBPP cases occur in women with infants <4500. g who are not diabetic and have no other identifiable risk factors. Furthermore, cesarean section reduces but does not completely eliminate the risk for NBPP. In this section, the relationship of these historic obstetric risk factors to the occurrence of NBPP is further explored. © 2014 Elsevier Inc.


Elkayam U.,University of Southern California
Journal of the American College of Cardiology | Year: 2011

Peripartum cardiomyopathy is a pregnancy-associated myocardial disease characterized by the development of heart failure due to marked left ventricular systolic dysfunction. Although the disease is relatively uncommon, its incidence is increasing, and it can be associated with important and lasting morbidity and with mortality. Peripartum cardiomyopathy seems to affect women in different parts of the world but with considerable differences in clinical presentation. The purposes of this review are to describe the clinical profile of peripartum cardiomyopathy in the United States and to provide recommendations for the diagnosis and the management of this disease. © 2011 American College of Cardiology Foundation.


Stohl W.,University of Southern California
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: The B-cell activating factor (BAFF) axis comprises two ligands (BAFF and APRIL) and three receptors (BCMA, TACI, BR3). BAFF is a vital B-cell survival factor and overexpression of BAFF in both mice and humans is associated with systemic lupus erythematosus (SLE). The anti-BAFF monoclonal antibody (mAb), belimumab, was recently approved by the US FDA for the treatment of adult SLE patients, and three additional BAFF antagonists (atacicept, blisibimod, tabalumab) are presently being evaluated in SLE Phase-III trials. Areas covered: The general biological properties of the individual elements of the BAFF/APRIL axis are reviewed, with emphasis placed on molecular interactions and the potential relevance of each individual element to SLE. Expert opinion: The success of belimumab, an agent which promotes only modest B-cell depletion, is contrasted with the failure of the anti-CD20 mAb rituximab, an agent which promotes profound B-cell depletion, and multiple arguments are offered to explain this apparent paradox. Real and perceived limitations to belimumab therapy are presented, and possibilities for other therapeutic agents that target specific elements of the BAFF/APRIL axis are discussed. © 2014 Informa UK, Ltd.


Ben-Zion Y.,University of Southern California
Geophysical Journal International | Year: 2012

Non-Volcanic Tremor (NVT) and related relatively weak and slow slip events termed Episodic Tremor and Slip (ETS) are observed below the seismogenic sections of numerous subduction zones and several major strike-slip faults. These events have various characteristics that distinguish them from regular tectonic earthquakes. Here we show that a frictional fault in elastic solid with a region below the seismogenic zone having on average a critical (near-)zero weakening during slip provides a simple unified explanation for the diverse observed phenomenology of NVT-ETS. The results imply that NVT-ETS have little predictive power on the occurrence of large events in the overriding seismogenic zone. Additional model predictions that may be tested with future high-resolution observations are fractal slip distributions and failure areas, discrete power-law frequency-moment statistics with exponent 3/2 and exponential tapering, overall scale-invariant potency/moment/magnitude time histories, triggered periodic NVT with evolving size and rate correlated with the stressing rate of the periodic triggering mechanisms, and parabolic (or exponential) source time functions for event sizes measured by duration (or moment/potency). © 2012 The Authors Geophysical Journal International © 2012 RAS.


Langdon T.G.,University of Southampton | Langdon T.G.,University of Southern California
Acta Materialia | Year: 2013

Twenty-five years ago, in 1988, there appeared a classic description of the application of severe plastic deformation (SPD) to bulk solids in order to achieve exceptional grain refinement to the submicrometer level. This report and later publications initiated considerable interest in materials science laboratories around the world and many experiments were subsequently performed to evaluate the principles and practice of SPD processing. The present report provides an overview of the more recent developments in this field, with special emphasis on the opportunities for achieving homogeneity in the as-processed materials and on the general characteristics of the mechanical properties achieved after SPD processing. For simplicity, special emphasis is placed on the two techniques of equal-channel angular pressing and high-pressure torsion as these are currently the most popular procedures for applying SPD processing. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Xu S.,University of Michigan | Sankar S.,University of Southern California | Neamati N.,University of Michigan
Drug Discovery Today | Year: 2014

Protein disulfide isomerase (PDI) has a key role in maintaining cellular homeostasis by mediating oxidative protein folding. It catalyzes disulfide bond formation, breakage and rearrangement in the endoplasmic reticulum and has chaperone protein activity. Increasing evidence suggests that PDI supports the survival and progression of several cancers. During the past decade, robust PDI activity assays have been developed and several PDI inhibitors identified, but none has been approved for clinical use. Herein, we review current knowledge of the role of PDI in cancer and discuss various assays for measuring the activities of PDI, highlighting their sensitivities and usefulness for high-throughput screening. The previously reported PDI inhibitors require further validation to serve as bona fide leads and additional optimization to generate novel drug candidates for clinical studies. © 2013 Elsevier Ltd.


Eisenberg L.S.,University of Southern California
Hearing Research | Year: 2014

William F. House was a pioneer in the evolving field of cochlear implants and auditory brainstem implants. Because of his vision, innovation and perseverance, the way was paved for future clinicians and researchers to carry on the work and advance a field that has been dedicated to serving adults and children with severe to profound hearing loss. Several of William House's contributions are highlighted in this prestigious volume to honor the recipients of the 2013 Lasker-Debakey Clinical Medical Research Award. Discussed are the early inventive years, clinical trials with the single-channel cochlear implant, the team approach, pediatric cochlear implantation, and the auditory brainstem implant. Readers may be surprised to learn that those early contributions continue to have relevance today.This article is part of a Special Issue entitled . © 2014 Elsevier B.V.


Majchrzak A.,University of Southern California | Malhotra A.,University of North Carolina
Journal of Strategic Information Systems | Year: 2013

Recent years have seen an increasing emphasis on open innovation by firms to keep pace with the growing intricacy of products and services and the ever changing needs of the markets. Much has been written about open innovation and its manifestation in the form of crowdsourcing. Unfortunately, most management research has taken the information system (IS) as a given. In this essay we contend that IS is not just an enabler but rather can be a shaper that optimizes open innovation in general and crowdsourcing in particular. This essay is intended to frame crowdsourcing for innovation in a manner that makes more apparent the issues that require research from an IS perspective. In doing so, we delineate the contributions that the IS field can make to the field of crowdsourcing. © 2013 Elsevier B.V. All rights reserved.


Stevens W.G.,University of Southern California
Aesthetic Surgery Journal | Year: 2015

Background: Vacuum applicators have been effective for cryolipolysis of the abdomen, flanks, inner thighs, back, chest, and arms. However, the lateral thighs have not been easily treated because fat from this area cannot be easily drawn into a vacuum cup. Objectives: The authors investigated the safety and efficacy of a prototype applicator for treatment of "nonpinchable" fat in the lateral thighs. Methods: In this prospective, nonrandomized, interventional cohort, multicenter study, a 120-minute unilateral treatment with a prototype conformablesurface applicator was performed on 1 lateral thigh of 40 patients, with the contralateral thigh serving as the control. During follow-up visits at 2 and 4 months, fat reduction was assessed by ultrasound imaging and clinical photography, and patient satisfaction surveys were completed. Results: Ultrasound data indicated a 2.6-mm mean normalized reduction in fat thickness-a statistically significant reduction vs the untreated control thigh (P = 7.8E-8). According to patient survey responses, 89% of patients would recommend the procedure to a friend; 86% were satisfied with cryolipolysis for the lateral thighs; 86% noticed visible fat reduction; and 97% were likely to undergo a second treatment. A panel of 3 independent blinded physicians correctly identified baseline and posttreatment clinical photographs in 87% of cases. There were no serious adverse events or unanticipated adverse device effects. Conclusions: The cryolipolysis conformable-surface applicator was safe and efficacious for treatment of lateral thigh fat. Clinical photographs and ultrasound results showed significant reduction in fat thickness, and noticeable reduction in undesirable "saddlebag" bulges. © 2015 The American Society for Aesthetic Plastic Surgery, Inc.


Quantitative understanding of variability in weathering fluxes on the modern Earth is limited because little is known about where the most important weathering reactions take place. This is partly because the locus of weathering is difficult to measure empirically. Inverse analysis of a parametric model presented here provides first-order constraints on variability in the thickness of the zone of active weathering. Results suggest that the effective thickness of the weathering zone varies relatively little across several orders of magnitude of denudation rate. At low to moderate denudation rates, reactions in soils may dominate weathering fluxes at the catchment scale, but the contribution from soil weathering decreases at higher denudation rates. Consequently, increased erosion leads to higher weathering fluxes, sustained by progressively greater contributions from weathering in bedrock. The effect of climate (temperature and runoff) on weathering fluxes is apparently weaker at low denudation rates than at high denudation rates, such that erosion, and potentially associated bedrock weathering, may be important for maintaining climate-stabilizing feedbacks in Earth's carbon cycle. © 2012 Geological Society of America.


LaRowe D.E.,University of Southern California
ISME Journal | Year: 2016

The environmental conditions that describe an ecosystem define the amount of energy available to the resident organisms and the amount of energy required to build biomass. Here, we quantify the amount of energy required to make biomass as a function of temperature, pressure, redox state, the sources of C, N and S, cell mass and the time that an organism requires to double or replace its biomass. Specifically, these energetics are calculated from 0 to 125 °C, 0.1 to 500 MPa and −0.38 to +0.86 V using CO2, acetate or CH4 for C, NO3 - or NH4 + for N and SO4 2- or HS- for S. The amounts of energy associated with synthesizing the biomolecules that make up a cell, which varies over 39 kJ (g cell)-1, are then used to compute energy-based yield coefficients for a vast range of environmental conditions. Taken together, environmental variables and the range of cell sizes leads to a ~4 orders of magnitude difference between the number of microbial cells that can be made from a Joule of Gibbs energy under the most (5.06 × 1011 cells J-1) and least (5.21 × 107 cells J-1) ideal conditions. When doubling/replacement time is taken into account, the range of anabolism energies can expand even further.The ISME Journal advance online publication, 9 February 2016; doi:10.1038/ismej.2015.227. © 2016 International Society for Microbial Ecology


Levander A.,Rice University | Miller M.S.,University of Southern California
Geochemistry, Geophysics, Geosystems | Year: 2012

We have produced common conversion point (CCP) stacked Ps and Sp receiver function image volumes of the Moho and lithosphere-asthenosphere boundary (LAB) beneath the western United States using Transportable Array data. The large image volumes and the diversity of tectonic environments they encompass allow us to investigate evolution of these structural discontinuities. The Moho is a nearly continuous topographic surface, whereas the LAB is not and the seismic images show a more complex expression. The first order change in LAB depth in the western U.S. occurs along the Cordilleran hingeline, the former Laurasian passive margin along the southwestern Precambrian North American terranes. The LAB is about 50% deeper to the east of the hingeline than to the west, with most of the increase in LAB thickness being in the mantle lithosphere. We infer that the Moho and the LAB are Late Mesozoic or Cenozoic everywhere west of the hingeline, modified during Farallon subduction and its aftermath. Between the hingeline and the Rocky Mountain Front, the LAB, and to a lesser extent the Moho, have been partially reset during the Cenozoic by processes that continue today. Seismicity and recent volcanism in the interior of the western U.S. are concentrated along gradients in crustal and/or lithospheric thickness, for example the hingeline, and the eastern edge of the coastal volcanic-magmatic terranes. To us this suggests that lateral gradients in integrated lithospheric strength focus deformation. Similarly, areas conjectured to be the sites of convective downwellings and associated volcanism are located along gradients in regional lithosphere thickness. © 2012. American Geophysical Union.


Asahina K.,University of Southern California
Journal of Gastroenterology and Hepatology (Australia) | Year: 2012

Hepatic stellate cells (HSCs) are recognized as a major player in liver fibrogenesis. Upon liver injury, HSCs differentiate into myofibroblasts and participate in progression of fibrosis and cirrhosis. Additional cell types such as resident liver fibroblasts/myofibroblasts or bone marrow cells are also known to generate myofibroblasts. One of the major obstacles to understanding the mechanism of liver fibrogenesis is the lack of knowledge regarding the developmental origin of HSCs and other liver mesenchymal cells. Recent cell lineage analyses demonstrate that HSCs are derived from mesoderm during liver development. MesP1-expressing mesoderm gives rise to the septum transversum mesenchyme before liver formation and then to the liver mesothelium and mesenchymal cells, including HSCs and perivascular mesenchymal cells around the veins during liver development. During the growth of embryonic liver, the mesothelium, consisting of mesothelial cells and submesothelial cells, migrates inward from the liver surface and gives rise to HSCs and perivascular mesenchymal cells, including portal fibroblasts, smooth muscle cells around the portal vein, and fibroblasts around the central vein. Cell lineage analyses indicate that mesothelial cells are HSC progenitor cells capable of differentiating into HSCs and other liver mesenchymal cells during liver development. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.


Quintana M.A.,Berry Consultants | Conti D.V.,University of Southern California
Statistics in Medicine | Year: 2013

We are interested in developing integrative approaches for variable selection problems that incorporate external knowledge on a set of predictors of interest. In particular, we have developed an integrative Bayesian model uncertainty (iBMU) method, which formally incorporates multiple sources of data via a second-stage probit model on the probability that any predictor is associated with the outcome of interest. Using simulations, we demonstrate that iBMU leads to an increase in power to detect true marginal associations over more commonly used variable selection techniques, such as least absolute shrinkage and selection operator and elastic net. In addition, iBMU leads to a more efficient model search algorithm over the basic BMU method even when the predictor-level covariates are only modestly informative. The increase in power and efficiency of our method becomes more substantial as the predictor-level covariates become more informative. Finally, we demonstrate the power and flexibility of iBMU for integrating both gene structure and functional biomarker information into a candidate gene study investigating over 50 genes in the brain reward system and their role with smoking cessation from the Pharmacogenetics of Nicotine Addiction and Treatment Consortium. © 2013 John Wiley & Sons, Ltd.


Mattingly C.,University of Southern California
The Paradox of Hope: Journeys through a Clinical Borderland | Year: 2010

Grounded in intimate moments of family life in and out of hospitals, this book explores the hope that inspires us to try to create lives worth living, even when no cure is in sight. The Paradox of Hope focuses on a group of African American families in a multicultural urban environment, many of them poor and all of them with children who have been diagnosed with serious chronic medical conditions. Cheryl Mattingly proposes a narrative phenomenology of practice as she explores case stories in this highly readable study. Depicting the multicultural urban hospital as a border zone where race, class, and chronic disease intersect, this theoretically innovative study illuminates communities of care that span both clinic and family and shows how hope is created as an everyday reality amid trying circumstances. © 2010 by The Regents of the University of California.


Thomas D.C.,University of Southern California
American Journal of Epidemiology | Year: 2014

Cumulative exposure-the product of intensity and duration for a constant exposure rate or its integral over time if variable-has been widely used in epidemiologic analyses of extended exposures, for example, the "pack-years" variable for tobacco smoking. Although the effects of intensity and duration are known to differ for exposures like smoking and ionizing radiation and simple cumulative exposure does not explicitly allow for modification by other time-related variables, such as age at exposure or time since exposure, the cumulative exposure variable has the merit of simplicity and has been shown to be one of the best predictors for many exposure-response relationships. This commentary discusses recent refinements of the pack-years variable, as discussed in this issue of the Journal by Vlaanderen et al. (Am J Epidemiol. 2014;179(3):290-298), in the broader context of general exposure-time-response relationships. © 2013 The Author.


Ananny M.,University of Southern California
Science Technology and Human Values | Year: 2016

Part of understanding the meaning and power of algorithms means asking what new demands they might make of ethical frameworks, and how they might be held accountable to ethical standards. I develop a definition of networked information algorithms (NIAs) as assemblages of institutionally situated code, practices, and norms with the power to create, sustain, and signify relationships among people and data through minimally observable, semiautonomous action. Starting from Merrill’s prompt to see ethics as the study of “what we ought to do,” I examine ethical dimensions of contemporary NIAs. Specifically, in an effort to sketch an empirically grounded, pragmatic ethics of algorithms, I trace an algorithmic assemblage’s power to convene constituents, suggest actions based on perceived similarity and probability, and govern the timing and timeframes of ethical action. © 2015, © The Author(s) 2015.


Mendel J.M.,University of Southern California
IEEE Transactions on Fuzzy Systems | Year: 2010

This comment points out a misnomer and two errors in a previous paper by the author ( IEEE Trans. Fuzzy Syst., vol. 17, no. 5, pp. 11891207, Oct. 2009), and because one of the errors relates the term " α-plane" to the term "z -slice," it also connects these two terms more correctly. © 2006 IEEE.


Spielman D.A.,Yale University | Teng S.-H.,University of Southern California
SIAM Journal on Computing | Year: 2011

We introduce a new notion of graph sparsification based on spectral similarity of graph Laplacians: spectral sparsification requires that the Laplacian quadratic form of the sparsifier approximate that of the original. This is equivalent to saying that the Laplacian of the sparsifier is a good preconditioner for the Laplacian of the original. We prove that every graph has a spectral sparsifier of nearly linear size. Moreover, we present an algorithm that produces spectral sparsifiers in time O(mlog c m), where m is the number of edges in the original graph and c is some absolute constant. This construction is a key component of a nearly linear time algorithm for solving linear equations in diagonally dominant matrices. Our sparsification algorithm makes use of a nearly linear time algorithm for graph partitioning that satisfies a strong guarantee: if the partition it outputs is very unbalanced, then the larger part is contained in a subgraph of high conductance. © 2011 Society for Industrial and Applied Mathematics.


Fabbri M.,University of Southern California | Fabbri M.,Gene Therapy Unit
Current Molecular Medicine | Year: 2013

MicroRNAs (miRNAs) are de-regulated in cancer versus the normal tissue counterpart and actively participate in human carcinogenesis. Among the genes whose expression is under their control there are both oncogenes and tumor suppressor genes, revealing that it is not only limiting but simply wrong to assign them a function just as oncogenes or as tumor suppressor genes. In addition to primary tumors, miRNAs can be detected in almost all human body fluids and effectively help to diagnose cancer and to prognosticate clinical outcome and response to treatment of tumors. The advent of miRNA mimic and miRNA silencing molecules has allowed to modulate miRNA expression in tumors, showing that miRNAs can be effectively used as therapeutic agents. This review will focus on those findings that have provided the rationale for the use of miRNAs as patient "tailored" anti-cancer agents. © 2013 Bentham Science Publishers.


Ghaffari A.,University of Southern California
American Journal of Kidney Diseases | Year: 2012

Background: Compared with hemodialysis, peritoneal dialysis (PD) is a cost-effective and patient-centered option with an early survival advantage, yet only 7% of patients with end-stage renal disease in the United States receive PD. PD underutilization is due in part to nephrologists' unfamiliarity with directly starting PD in patients who present with kidney failure requiring urgent initiation of dialysis. Design: Quality improvement report. Setting & Participants: Single-center study whereby 18 patients who presented urgently with chronic kidney disease stage 5 without a plan for dialysis modality were offered PD as the initial modality of dialysis. Concurrently, 9 patients started on PD therapy nonurgently were included as the comparative group. Quality Improvement Plan: An urgent-start PD program was developed to support and standardize the process by which patients without a plan for dialysis modality were started on PD. This included rapid PD access placement, PD nursing education, and administrative support. Standardized protocols were created for modality selection, initial prescription, and prevention and management of complications. Measures: Short-term (90-day) clinical outcomes (Kt/V, hemoglobin, iron saturation, parathyroid hormone, phosphorus, calcium, and albumin) and complications (peritonitis, exit-site infections, leaks, and catheter malfunction) were compared between the urgent-start and nonurgent-start PD groups. Results: Short-term clinical outcomes were similar between the 2 groups for all parameters except uncorrected serum calcium level, which was lower in the urgent-start group (P = 0.02). Peritonitis, exit-site infection, catheter-related complications, and other complications were similar between the 2 groups, although the number of minor leaks was higher in the urgent-start group. Limitations: This is a single-center nonrandomized study with a small sample size. Conclusions: Our structured program shows safety and feasibility in starting PD in patients with kidney failure who present without a plan for dialysis modality. The steps laid out in this report can provide the framework for creating local urgent-start PD programs. © 2012 National Kidney Foundation, Inc.


Freyer D.R.,Childrens Center for Cancer and Blood Diseases | Freyer D.R.,University of Southern California
Journal of Clinical Oncology | Year: 2010

Purpose: Young adult survivors of childhood and adolescent cancer are an ever-growing population of patients, many of whom remain at lifelong risk for potentially serious complications of their cancer therapy. Yet research shows that many of these older survivors have deficient health-related knowledge and are not engaging in recommended health promotion and screening practices that could improve their long-term outcomes. The purpose of this review is to address these disparities by discussing how formal transition of care from pediatric to adult-focused survivorship services may help meet the unique medical, developmental, and psychosocial challenges of these young adults. Design: Literature review and discussion. Results: This article summarizes current research documenting the medical needs of young adult survivors, their suboptimal compliance with recommended follow-up, and the rationale, essential functions, current models, and innovative approaches for transition of follow-up care. Conclusion: Systematic health care transition constitutes the standard of care for young adult survivors of childhood cancer. In developing a transitional care program, it is necessary to consider the scope of services to be provided, available resources, and other local exigencies that help determine the optimal model for use. Additional research is needed to improve health services delivery to this population. Effective advocacy is needed, particularly in the United States, to ensure the availability of uninterrupted health insurance coverage for survivorship services in young adulthood. © 2010 by American Society of Clinical Oncology.


Elyse Schauwecker P.,University of Southern California
PLoS ONE | Year: 2010

Background: Galanin is a neuropeptide with a wide distribution in the central and peripheral nervous systems and whose physiological effects are mediated through three G protein-coupled receptor subtypes, GalR1, GalR2, and GalR3. Several lines of evidence indicate that galanin, as well as activation of the GalR1 receptor, is a potent and effective modulator of neuronal excitability in the hippocampus. Methodology/Principal Findings: In order to test more formally the potential influence of GalR1 on seizure-induced excitotoxic cell death, we conducted functional complementation tests in which transgenic mice that exhibit decreased expression of the GalR1 candidate mRNA underwent kainate-induced status epilepticus to determine if the quantitative trait of susceptibility to seizure-induced cell death is determined by the activity of GalR1. In the present study, we report that reduction of GalR1 mRNA via null mutation or injection of the GalR1 antagonist, galantide, prior to kainate-induced status epilepticus induces hippocampal damage in a mouse strain known to be highly resistant to kainate-induced neuronal injury. Wild-type and GalR1 knockout mice were subjected to systemic kainate administration. Seven days later, Nissl and NeuN immune- staining demonstrated that hippocampal cell death was significantly increased in GalR1 knockout strains and in animals injected with the GalR1 antagonist. Compared to GalR1-expressing mice, GalR1-deficient mice had significantly larger hippocampal lesions after status epilepticus. Conclusions/Significance: Our results suggest that a reduction of GalR1 expression in the C57BL/6J mouse strain renders them susceptible to excitotoxic injury following systemic kainate administration. From these results, GalR1 protein emerges as a new molecular target that may have a potential therapeutic value in modulating seizure-induced cell death. © 2010 P. Elyse Schauwecker.


Morency L.-P.,University of Southern California
IEEE Signal Processing Magazine | Year: 2010

Face-to-face communication is a highly interactive process where participants mutually exchange and interpret verbal and nonverbal messages. Communication dynamics represent the temporal relationship between these communicative messages. Even when only one person speaks at a time, other participants exchange information continuously among themselves and with the speaker through gesture, gaze, posture, and facial expressions. The transactional view of human communication shows an important dynamic between communicative behaviors where each person serves simultaneously as speaker and listener [9]. At the same time you send a message, you also receive messages from your own communications (individual dynamics) as well as from the reactions of the other person(s) (interpersonal dynamics) [2]. © 2010 IEEE.


Haldar J.P.,University of Southern California
IEEE Transactions on Medical Imaging | Year: 2014

Recent theoretical results on low-rank matrix reconstruction have inspired significant interest in low-rank modeling of MRI images. Existing approaches have focused on higher-dimensional scenarios with data available from multiple channels, timepoints, or image contrasts. The present work demonstrates that single-channel, single-contrast, single-timepoint k-space data can also be mapped to low-rank matrices when the image has limited spatial support or slowly varying phase. Based on this, we develop a novel and flexible framework for constrained image reconstruction that uses low-rank matrix modeling of local k-space neighborhoods (LORAKS). A new regularization penalty and corresponding algorithm for promoting low-rank are also introduced. The potential of LORAKS is demonstrated with simulated and experimental data for a range of denoising and sparse-sampling applications. LORAKS is also compared against state-of-the-art methods like homodyne reconstruction, \ell1-norm minimization, and total variation minimization, and is demonstrated to have distinct features and advantages. In addition, while calibration-based support and phase constraints are commonly used in existing methods, the LORAKS framework enables calibrationless use of these constraints. © 1982-2012 IEEE.


Chakrabarti S.,University of Southern California
Journal of Transport Geography | Year: 2015

This study explores the role of service reliability in determining bus transit ridership. Using stop level service supply, demand, and performance data from the Los Angeles Metro bus system, I investigate whether reliability of a directional line serving a stop influences the number of passengers boarding the line at that stop, controlling for various other established factors affecting demand. This cross-sectional analysis of the variation in line boardings across about 1300 sample schedule time point bus stops served by about 300 directional bus lines over a six-month period uses a historical archive of real-time geo-referenced vehicle location data, and focuses on five different time periods, peaks and off-peaks, of a typical weekday. By evaluating two measures that capture different dimensions of bus service reliability, and by estimating a series of regression models, I find systematic evidence that higher average service punctuality (or schedule adherence) and lower variation in schedule deviation over time are associated with greater ridership, all else equal, particularly during the peak periods. This study also provides first empirical evidence that the effect of reliability on peak-period ridership is moderated by headway. The demand for reliability seems to be higher for lines with relatively longer headways. The findings indicate that service reliability influences transit mode choice and/or line/route selection, and suggest that system-wide ridership gains can be expected from reliability improvements. From an urban planning perspective, this study provides more evidence that good service quality can effectively compliment transformations in the urban fabric brought about by coordinated land use - transit plans to promote transit use. © 2015 Elsevier Ltd.


Gupta R.,University of Southern California
Seminars in cutaneous medicine and surgery | Year: 2013

Body dysmorphic disorder (BDD) is a DSM-IV disorder that is characterized by a distressing and excessive preoccupation with a slight or imagined defect of a physical feature. BDD causes significant impairment of psychosocial functioning and a decreased quality of life for patients. Though the disorder is commonly seen in the dermatology setting, the disease remains under recognized and under-treated. It is important for dermatologists to be aware of BDD as patients suffer greatly from the disease. In this review, we provide an update on the epidemiology, clinical features, and treatment options for BDD.


Endres D.B.,University of Southern California
Clinical Biochemistry | Year: 2012

Hypercalcemia is a relatively common clinical finding. Primary hyperparathyroidism, hypercalcemia associated with malignancy and chronic renal failure (with calcium and vitamin D metabolite treatment or tertiary hyperparathyroidism) are the most common causes. Less common causes of hypercalcemia include vitamin D-related (granulomatous diseases, lymphoma, vitamin D intoxication), other endocrine (thyrotoxicosis), medications (milk-alkali, thiazides, lithium) and other causes (immobilization, familial hypocalciuric hypercalcemia). The clinical laboratory is central to the diagnosis and differential diagnosis of hypercalcemia. Its role has expanded from measuring routine chemistry tests such as total calcium, phosphate, creatinine and alkaline phosphate to include quantification of ionized calcium, parathyroid hormone (PTH) and vitamin D metabolites. In spite of this progress, the diagnosis and differential diagnosis of hypercalcemia can be significantly improved by: 1) increasing the availability and utilization of ionized calcium since total and corrected calcium are often inaccurate; 2) establishing more accurate reference intervals for parathyroid hormone by excluding individuals who are vitamin D insufficient or deficient; and 3) harmonizing intact PTH immunoassays. © 2012.


Elkayam U.,University of Southern California
Journal of the American College of Cardiology | Year: 2014

Peripartum cardiomyopathy (PPCM) is a pregnancy-associated myocardial disease with marked left ventricular systolic dysfunction. Although this condition can lead to major complications, including severe heart failure, arrhythmias, thromboembolic events, and death, the majority of women with this condition demonstrate a complete or partial recovery. Many of these women desire to become pregnant again and are concerned regarding the safety of additional pregnancies. The purpose of this paper is to review the available information related to subsequent pregnancies in women with a history of PPCM in an attempt to reach conclusions regarding the risk of such pregnancies in this group of patients. © 2014 American College of Cardiology Foundation.


Becker T.W.,University of Southern California
Geochemistry, Geophysics, Geosystems | Year: 2012

In recent years, a number of relatively high resolution seismic tomography models for the uppermost mantle underneath the western United States have been published, and vigorous debate has ensued about their tectonic interpretation. I present a straightforward, yet quantitative, comparison between models in order to help establish a framework for geodynamic interpretation, and to help judge the role of tomographic theory vs. data selection. Mapped S and P wave anomalies are found to be remarkably consistent between models, which implies that seismologists are beginning to narrow down the structure underneath active continental margins to scales of ∼200 km. Large discrepancies between published anomaly amplitudes exist, however, and the models on the high end of the spectrum raise questions as to how they are to be interpreted in terms of temperature, composition, and melting. Copyright © 2012 by the American Geophysical Union.


Jadvar H.,University of Southern California
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Prostate cancer is a major public health problem in developed countries. The remarkable biological and clinical heterogeneity of prostate cancer provides unique opportunities as well as challenges for the diagnostic imaging evaluation of this prevalent disease. The disease is characterized by a natural history that ranges from localized slowly growing hormone-dependent tumor progressing to metastatic hormone-refractory disease. PET is an ideal imaging tool for noninvasive interrogation of the underlying tumor biology. 18F-FDG is the most common PET radiotracer used for oncological applications based upon elevated glucose metabolism in malignant tissue in comparison to normal tissue. FDG uptake in prostate cancer depends on tumor differentiation with low accumulation in well-differentiated tumors and high uptake in aggressive poorly differentiated tumors. Cumulative current evidence suggests that FDG PET may be useful in detection of disease in a small fraction of patients with biochemical recurrence, in the imaging evaluation of extent and treatment response in metastatic disease and in prediction of patient outcome. © 2013 Springer-Verlag Berlin Heidelberg.


Valdesolo P.,Claremont McKenna College | Graham J.,University of Southern California
Psychological Science | Year: 2014

Across five studies, we found that awe increases both supernatural belief (Studies 1, 2, and 5) and intentional-pattern perception (Studies 3 and 4)-two phenomena that have been linked to agency detection, or the tendency to interpret events as the consequence of intentional and purpose-driven agents. Effects were both directly and conceptually replicated, and mediational analyses revealed that these effects were driven by the influence of awe on tolerance for uncertainty. Experiences of awe decreased tolerance for uncertainty, which, in turn, increased the tendency to believe in nonhuman agents and to perceive human agency in random events. © The Author(s) 2013.


DeMeester S.R.,University of Southern California
Annals of Thoracic Surgery | Year: 2010

A vagal sparing esophagectomy should be considered for patients with end-stage benign disease and Barrett's high-grade dysplasia or intramucosal adenocarcinoma. No lymphadenectomy is performed with this procedure, so it is not applicable to cancers invasive into the submucosa. Advantages of a vagal-sparing procedure over a standard esophagectomy with gastric pull-up include its simplicity to perform, ability to be done as a laparoscopic procedure, lack of requirement for single-lung ventilation or mediastinal dissection, avoidance of the need for a pyloroplasty, and preservation of the vagus nerves. Given these advantages, a vagal-sparing esophagectomy should be the preferred method of esophageal resection in appropriate patients. © 2010 The Society of Thoracic Surgeons.


Perez I.A.,University of Southern California
Respiratory physiology & neurobiology | Year: 2013

Congenital central hypoventilation syndrome is a rare disorder caused by a mutation in the PHOX2B gene resulting in hypoventilation that is worse during sleep. Human physiologic studies show that patients with CCHS have absent or decreased rebreathing ventilatory responses to hypercapnia and hypoxemia during sleep as well as during wakefulness. Some ventilatory responses to hypoxia and hyperoxia can be demonstrated using a step change in inspired oxygen. However, these suggest that both central and peripheral chemoreceptor functions are generally defective in all states in children with CCHS. The defect in CCHS may lie in central nervous system pathways regulating ventilation, whose development and function are controlled by PHOX2B. Moreover, the retrotrapezoid nucleus (RTN) may be the major defect in CCHS, where central and peripheral inputs converge. Human physiological studies predicted that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals. New evidence suggests the RTN may be the respiratory controller where chemoreceptor inputs are integrated. In this review we present the clinical presentation of CCHS, revisit results of human physiologic studies, and discuss the findings in light of new knowledge about the role of PHOX2B and RTN in CCHS. Copyright © 2012 Elsevier B.V. All rights reserved.


Russell C.A.,University of Southern California
American Journal of Surgery | Year: 2014

Breast cancer remains the most common cancer diagnosed in women in the United States and is second only to lung cancer as a cause of cancer mortality. Breast cancer has become the prototypical solid tumor where targets have been identified within the tumor allowing for a personalized approach of systemic therapy. © 2014 Elsevier Inc. All rights reserved.


Mallick P.,University of Southern California | Mallick P.,University of California at Los Angeles | Kuster B.,TU Munich | Kuster B.,Center for Integrated Protein Science Munich
Nature Biotechnology | Year: 2010

The evolution of mass spectrometry-based proteomic technologies has advanced our understanding of the complex and dynamic nature of proteomes while concurrently revealing that no 'one-size-fits-all' proteomic strategy can be used to address all biological questions. Whereas some techniques, such as those for analyzing protein complexes, have matured and are broadly applied with great success, others, such as global quantitative protein expression profiling for biomarker discovery, are still confined to a few expert laboratories. In this Perspective, we attempt to distill the wide array of conceivable proteomic approaches into a compact canon of techniques suited to asking and answering specific types of biological questions. By discussing the relationship between the complexity of a biological sample and the difficulty of implementing the appropriate analysis approach, we contrast areas of proteomics broadly usable today with those that require significant technical and conceptual development. We hope to provide nonexperts with a guide for calibrating expectations of what can realistically be learned from a proteomics experiment and for gauging the planning and execution effort. We further provide a detailed supplement explaining the most common techniques in proteomics. © 2010 Nature America, Inc. All rights reserved.


Campese V.M.,University of Southern California
Seminars in Nephrology | Year: 2014

Hypertension associated with chronic kidney diseases often is resistant to drug treatment. This review deals with two main aspects of the management of CKD patients with hypertension: the role of sodium/volume and the need for dietary salt restriction, as well as appropriate use of diuretics and what currently is called sequential nephron blockade; the second aspect that is addressed extensively in this review is the role of the sympathetic nervous system and the possible clinical use of renal denervation. © 2014 Elsevier Inc.


Chen A.Y.,University of Southern California
Medical care | Year: 2012

Consumer assessment of health care is an important metric for evaluating quality of care. These assessments can help purchasers, health plans, and providers deliver care that fits patients' needs. To examine differences in reports and ratings of care delivered to adults and children and whether they vary by site. This observational study compares adult and child experiences with care at a large west coast medical center and affiliated clinics and a large mid-western health plan using Consumer Assessment of Healthcare Providers and Systems Clinician & Group 1.0 Survey data. Office staff helpfulness and courtesy was perceived more positively for adult than pediatric care in the west coast site. In contrast, more positive perceptions of pediatric care were observed in both sites for coordination of care, shared decision making, overall rating of the doctor, and willingness to recommend the doctor to family and friends. In addition, pediatric care was perceived more positively in the mid-west site for access to care, provider communication, and office staff helpfulness and courtesy. The differences between pediatric care and adult care were larger in the mid-western site than the west coast site. There are significant differences in the perception of care for children and adults with care provided to children tending to be perceived more positively. Further research is needed to identify the reasons for these differences and provide more definitive information at sites throughout the United States.


Zhang H.,University of Southern California
Operations Research | Year: 2012

This paper studies an infinite horizon adverse selection model with an underlying Markov information process. It introduces a graphic representation of continuation contracts and continuation payoff frontiers, namely finite policy graph, and provides an algorithm to approximate the optimal policy graph through iterations. The algorithm performs an additional step after each value iteration - replacing dominated points on the previous continuation payoff frontier by points on the new frontier and reevaluating the new frontier. This dominance-free reevaluation step accelerates the convergence of the continuation payoff frontiers. Numerical examples demonstrate the effectiveness of this algorithm and properties of the optimal contracts. © 2012 INFORMS.


Pulsipher M.A.,University of Southern California
Blood | Year: 2016

In this issue of Blood, Jodele et al1 build upon earlier work on the role of complement in the pathophysiology2 and therapy3 of transplant-associated thrombotic microangiopathy (TA-TMA) by exploring genetic predisposition for developing this complication. Earlier work in atypical hemolytic uremic syndrome showed a number of alterations in genes that had been previously associated with the disease, along with gene variants in coagulation and other pathways that were likely associated with this condition.4 In a similar fashion, Jodele et al hone in on genetic risk for TA-TMA by looking for variants in 17 genes specifically known to play a role in complement activation in a cohort of 77 subjects undergoing hematopoietic cell transplantation, 34 of whom had developed TMA. © 2016 by The American Society of Hematology.


Broder J.,Cornell University | Rusmevichientong P.,University of Southern California
Operations Research | Year: 2012

We consider a stylized dynamic pricing model in which a monopolist prices a product to a sequence of T customers who independently make purchasing decisions based on the price offered according to a general parametric choice model. The parameters of the model are unknown to the seller, whose objective is to determine a pricing policy that minimizes the regret, which is the expected difference between the seller's revenue and the revenue of a clairvoyant seller who knows the values of the parameters in advance and always offers the revenue-maximizing price. We show that the regret of the optimal pricing policy in this model is φ(√T), by establishing an Ω(√T) lower bound on the worst-case regret under an arbitrary policy, and presenting a pricing policy based on maximum-likelihood estimation whose regret is (√T) across all problem instances. Furthermore, we show that when the demand curves satisfy a "well-separated" condition, the T -period regret of the optimal policy is φ(log T). Numerical experiments show that our policies perform well. © 2012 INFORMS.


Cogan A.M.,University of Southern California
American Journal of Occupational Therapy | Year: 2014

More than 2 million U.S. military servicemembers have deployed to Afghanistan or Iraq since September 11, 2001. Unlike during prior conflicts, many servicemembers leave spouses and children behind. Long, multiple deployments cause strain on family at home, with new challenges arising when servicemembers return from combat and reintegrate into family and civilian life. In World Wars I and II, occupational therapy practitioners played a significant role in supporting servicemember reintegration. However, their presence in program delivery in this practice area is limited. Occupational therapy researchers and practitioners can make a valuable contribution by helping families tailor daily activities and routines to address challenges and optimize health and wellness. However, barriers such as reimbursement for services, workforce availability, and access to military families have limited the profession's full engagement. Advocacy is needed to help establish occupational therapy as a key component of the mental and preventive health care teams serving military servicemembers.


Kloner R.A.,Heart Institute | Kloner R.A.,University of Southern California
Circulation Research | Year: 2013

There is continued interest in the concept of limiting myocardial infarct size with adjunctive agents administered along with reperfusion injury; however, there remains considerable controversy in the literature. The purpose of this article is to review the medical literature on clinical trials performed during the past 3 years that have attempted to reduce myocardial infarct size by administration of adjunctive therapies along with reperfusion therapy. A PubMed-driven literature search revealed a host of clinical trials focusing on the following prominent types of therapies: endogenous conditioning (postconditioning and remote ischemic conditioning); rapid cooling; pharmacological therapy (cyclosporine, abciximab, clopidogrel, tirofiban, erythropoietin, thrombus aspiration, adenosine, glucose-insulin-potassium, statins, antidiabetic agents, FX06, iron chelation, and ranolazine). Although there remains some controversy, quite a few of these studies showed that adjunctive therapy further reduced myocardial infarct size when coupled with reperfusion. Antiplatelet agents are emerging as some of the newest agents that seem to have cardioprotective capabilities. Postconditioning has become a bit more controversial in the clinical literature; remote conditioning, early and rapid cooling, adenosine, and ranolazine are intriguing therapies deserving of larger studies. Certain agents and maneuvers, such as erythropoietin, protein kinase C δ inhibitors, iron chelation, and intra-aortic balloon counterpulsation, perhaps should be retired. The correct adjunctive therapy administered along with reperfusion has the capability of further reducing myocardial injury during ST-segment-elevation myocardial infarction. © 2013 American Heart Association, Inc.


Christe K.O.,University of Southern California
Chemical Communications | Year: 2013

In 1962, Neil Bartlett published a terse note in Proc. Chem. Soc. eradicating the long held dogma that noble gases are inert and cannot form stable compounds. This historical discovery has revolutionized our views on chemistry and has given rise to thousands of papers on noble gas chemistry. The fact that his proposed reaction product "Xe+[PtF 6]-" has eluded experimental detection for more than half a century and actually was a mixture of XeF+ and Xe 2F3 + salts does not diminish the enormous impact of his discovery. A plausible explanation for the failures to observe "Xe+[PtF6]-" experimentally is presented. © The Royal Society of Chemistry 2013.


Ji C.,University of Southern California
Biochemistry Research International | Year: 2012

Alcohol is readily distributed throughout the body in the blood stream and crosses biological membranes, which affect virtually all biological processes inside the cell. Excessive alcohol consumption induces numerous pathological stress responses, part of which is endoplasmic reticulum (ER) stress response. ER stress, a condition under which unfolded/misfolded protein accumulates in the ER, contributes to alcoholic disorders of major organs such as liver, pancreas, heart, and brain. Potential mechanisms that trigger the alcoholic ER stress response are directly or indirectly related to alcohol metabolism, which includes toxic acetaldehyde and homocysteine, oxidative stress, perturbations of calcium or iron homeostasis, alterations of S-adenosylmethionine to S-adenosylhomocysteine ratio, and abnormal epigenetic modifications. Interruption of the ER stress triggers is anticipated to have therapeutic benefits for alcoholic disorders. Copyright © 2012 Cheng Ji.


Somma R.D.,Los Alamos National Laboratory | Boixo S.,University of Southern California
SIAM Journal on Computing | Year: 2013

Many problems can be solved by preparing a specific eigenstate of some Hamiltonian H. The generic cost of quantum algorithms for these problems is determined by the inverse spectral gap of H for that eigenstate and the cost of evolving with H for some fixed time. The goal of spectral gap amplification is to construct a Hamiltonian H′ with the same eigenstate as H but a bigger spectral gap, requiring that constant-time evolutions with H′ and H are implemented with nearly the same cost. We show that a quadratic spectral gap amplification is possible when H satisfies a frustration-free property and give H′ for these cases. This results in quantum speedups for optimization problems. It also yields improved constructions for adiabatic simulations of quantum circuits and for the preparation of projected entangled pair states, which play an important role in quantum many-body physics. Defining a suitable black-box model, we establish that the quadratic amplification is optimal for frustration-free Hamiltonians and that no spectral gap amplification is possible, in general, if the frustration-free property is removed. A corollary is that finding a similarity transformation between a stoquastic Hamiltonian and the corresponding stochastic matrix is hard in the black-box model, setting limits to the power of some classical methods that simulate quantum adiabatic evolutions. © 2013 Society for Industrial and Applied Mathematics.


Kaiser A.M.,University of Southern California
Diseases of the Colon and Rectum | Year: 2012

BACKGROUND: Continent ileostomy is an alternative for patients who are either not candidates for an ileo-anal pullthrough or in whom an ileo-anal pullthrough failed. We previously described a new type of continent ileostomy (T-pouch) with a nonintussuscepting valve. OBJECTIVE: This study performed an outcomes analysis of the first 10 years with 40 patients. DESIGN: A prospective database of patients with a Tpouch from 2000 to 2010 was retrospectively analyzed. MAIN OUTCOME MEASURES: The primary outcomes measured were demographics and surgical recovery information and the functional data obtained via questionnaire: incontinence, difficulty of pouch intubation, restrictions (work, social, diet, and sexual), quality of health and life, and level of satisfaction with surgery, which were rated on a scale of 0 to 10. RESULTS: Twenty-three women and 17 men (mean age, 51.2) received a T-pouch. Median follow-up was 6.2 years (range, 0.8-11 years). Five patients (12.5%) experience a leak; 3 leaks were managed conservatively and/or with drain placement. Pouch intubations were done 4 times per day in a mean of 6.8 minutes; the insertion difficulty was rated as 2.5 of 10. Ninety-two percent achieved good continence. All quality-of-life and dysfunction/restriction scores showed significant improvement. Major abdominal surgeries for pouch-related reasons were needed in 30%; minor service operations of the skin-level stoma were needed in 25% of the patients. Of the patients, 87.5% would do the surgery again; 90% would recommend it to others with the same diagnosis. LIMITATIONS: This study was limited by the cohort size and the lack of long-term data. CONCLUSION: Ten years with 40 patients confirmed that creation of a T-pouch is complex but could be performed with an acceptable rate of complications. It dramatically improved functional outcomes; most notably, it improved fecal control and decreased social, sexual, and work restrictions. © ASCRS 2012.


Haydn N.T.A.,University of Southern California
Dynamical Systems | Year: 2013

This paper reviews recent progress that has been made in the study of return times distribution. We discuss recent results on the first return time for systems with various mixing properties and then distribution results for higher order returns. We survey different techniques that have been used to obtain limiting results for higher order returns such as the moment method, the Chen-Stein method and total variation method. We also cover results that look at the limiting distribution at periodic points. Finally, we also look at the connection to recurrence times and results of the kind proven by Ornstein and Weiss two decades ago. Only positive entropy systems are considered. © 2013 Copyright Taylor and Francis Group, LLC.


Krylov A.I.,University of Southern California | Gill P.M.W.,Australian National University
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2013

Q-Chem is a general-purpose electronic structure package featuring a variety of established and new methods implemented using innovative algorithms that enable fast calculations of large systems on regular laboratory workstations using density functional and wave-function-based approaches. It features an integrated graphical interface and input generator, a large selection of functionals and correlation approaches including methods for electronically excited states and open-shell systems. In addition to serving the computational chemistry community, Q-Chem also provides an excellent development platform. © 2012 John Wiley & Sons, Ltd.


Spielman D.A.,Yale University | Teng S.-H.,University of Southern California
SIAM Journal on Computing | Year: 2013

We study the design of local algorithms for massive graphs. A local graph algorithm is one that finds a solution containing or near a given vertex without looking at the whole graph. We present a local clustering algorithm. Our algorithm finds a good cluster-a subset of vertices whose internal connections are significantly richer than its external connections-near a given vertex. The running time of our algorithm, when it finds a nonempty local cluster, is nearly linear in the size of the cluster it outputs. The running time of our algorithm also depends polylogarithmically on the size of the graph and polynomially on the conductance of the cluster it produces. Our clustering algorithm could be a useful primitive for handling massive graphs, such as social networks and webgraphs. As an application of this clustering algorithm, we present a partitioning algorithm that finds an approximate sparsest cut with nearly optimal balance. Our algorithm takes time nearly linear in the number edges of the graph. Using the partitioning algorithm of this paper, we have designed a nearly linear time algorithm for constructing spectral sparsifiers of graphs, which we in turn use in a nearly linear time algorithm for solving linear systems in symmetric, diagonally dominant matrices. The linear system solver also leads to a nearly linear time algorithm for approximating the secondsmallest eigenvalue and corresponding eigenvector of the Laplacian matrix of a graph. These other results are presented in two companion papers. © 2013 Society for Industrial and Applied Mathematics.


Jadvar H.,University of Southern California
American Journal of Roentgenology | Year: 2012

OBJECTIVE. Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION. In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. © American Roentgen Ray Society.


Templeman C.,University of Southern California
Current Opinion in Obstetrics and Gynecology | Year: 2012

Purpose of Review: This review will address the recent literature regarding adolescent endometriosis. Recent Findings: An increasing body of literature suggests that there are symptoms of endometriosis present in adolescents. In addition, those teens with a history of dysmenorrhea severe enough to disrupt quality of life are more likely to be diagnosed with endometriosis. Summary: The issues of endometriosis progression and early diagnosis remain key issues for the adolescent. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Naqvi T.Z.,University of Southern California
JACC: Cardiovascular Imaging | Year: 2010

Optimization of atrioventricular delay (AVD) and interventricular delay (VVD) in patients with a biventricular (Biv) pacemaker has been associated with improvement in cardiac output acutely, a reduction in heart failure symptoms, and improved exercise capacity. Several individual echocardiography (echo) Doppler parameters have been used for pacemaker optimization. In this review, pacemaker optimization based on echocardiographic evaluation of cardiac hemodynamics is presented. The goals of this paper are to discuss studies in echo-guided pacemaker optimization, provide a systemic guide to pacemaker interrogation and optimization in patients after Biv pacing who may have complex hemodynamic derangement, and finally, to discuss studies in optimization with exercise or atrial pacing. Case examples highlighting hemodynamic derangement in heart failure, tailoring of Biv pacemaker optimization to the underlying physiologic derangement, and its improvement with optimization are presented. © 2010 American College of Cardiology Foundation.


Schneider L.S.,University of Southern California | Insel P.S.,University of California at San Francisco | Weiner M.W.,University of California at San Francisco
Archives of Neurology | Year: 2011

Objectives: To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. Design: Cohort study. Setting: The 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants: Outpatients with MCI and AD in ADNI. Main Outcome Measures: The AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). Results: A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. Conclusions: Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration-approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. Study Registration: clinicalTrials.gov Identifier: NCT00106899 ©2011 American Medical Association. All rights reserved.


Stearns K.M.,University of Pittsburgh | Powers C.M.,University of Southern California
American Journal of Sports Medicine | Year: 2014

Background: Impaired hip muscle performance has been implicated as a contributing factor to the increased risk of anterior cruciate ligament (ACL) injury in women. Purpose: To determine the influence of a hip-focused training program on lower extremity biomechanics during a drop-jump task. Study Design: Descriptive laboratory study. Methods: Twenty-one recreationally active women (18-25 years of age) participated in a 4-week training program consisting of hip-focused plyometric and balance perturbation exercises (3 times/wk, 30 min/session). Maximum isometric strength of the hip extensors, hip abductors, and knee extensors was assessed, along with lower extremity biomechanics during a drop-jump task. All assessments were performed within 5 days of initiation and completion of the training program. Results: After training, subjects demonstrated significantly greater maximum isometric strength of the hip extensors (2.87 ± 0.7 vs 3.11 ± 0.7 N·m/kg; P<.01) and hip abductors (2.08 ± 0.7 vs 2.23 ± 0.07 N·m/kg; P = .004). No significant difference in knee extensor strength was observed. After training, subjects landed with significantly greater peak knee flexion (94.0° ± 8.5° vs 98.0° ± 10.1°; P<.001) and hip flexion (83.4° ± 7.6° vs 89.9° ± 8.8°; P = .008) and a lower knee/hip extensor moment ratio (1.33 ± 0.6 vs 0.99 ± 0.3; P = .001). In addition, subjects demonstrated significantly lower peak knee abduction angles (6.8° ± 3.3° vs 5.6° ± 3.1°; P = .04) and average knee adductor moments (0.06 ± 0.1 vs -0.02 ± 0.1 N·m/kg; P<.001). Conclusion: Changes in lower extremity biomechanics consistent with decreased risk for ACL injury were observed after participation in a hip-focused training program. Clinical Relevance: The study results suggest that ACL injury prevention programs targeting hip muscle performance may be important in mitigating biomechanical risk factors associated with ACL injury in women. © 2013 The Author(s).


The Drosophila melanogaster Piwi protein regulates both niche and intrinsic mechanisms to maintain germline stem cells, but its underlying mechanism remains unclear. Here we report that Piwi interacts with Polycomb group complexes PRC1 and PRC2 in niche and germline cells to regulate ovarian germline stem cells and oogenesis. Piwi physically interacts with the PRC2 subunits Su(z)12 and Esc in the ovary and in vitro. Chromatin coimmunoprecipitation of Piwi, the PRC2 enzymatic subunit E(z), histone H3 trimethylated at lysine 27 (H3K27me3) and RNA polymerase II in wild-type and piwi mutant ovaries demonstrates that Piwi binds a conserved DNA motif at ∼72 genomic sites and inhibits PRC2 binding to many non-Piwi-binding genomic targets and H3K27 trimethylation. Moreover, Piwi influences RNA polymerase II activities in Drosophila ovaries, likely via inhibiting PRC2. We hypothesize that Piwi negatively regulates PRC2 binding by sequestering PRC2 in the nucleoplasm, thus reducing PRC2 binding to many targets and influencing transcription during oogenesis. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Moradian-Oldak J.,University of Southern California
Frontiers in Bioscience | Year: 2012

Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth.


Li G.,Nanjing University | West A.J.,University of Southern California
Earth and Planetary Science Letters | Year: 2014

The Li isotopic record of seawater shows a dramatic increase of ~9s over the past ~60 million years. Here we use a model to explore what may have caused this change. We focus particularly on considering how changes in the "reverse weathering" sinks that remove Li from seawater can contribute to explain the observed increase. Our interpretation is based on dividing the oceanic sink, which preferentially removes light Li, into two components: (i) removal into marine authigenic clays in sediments at low temperatures, with associated high fractionation factors, and (ii) removal into altered oceanic basalt at higher temperatures and resulting lower fractionation factors. We suggest that increases in the flux of degraded continental material delivered to the oceans over the past 60 Ma could have increased removal of Li into sedimentary authigenic clays versus altered basalt. Because altered basalt is associated with a smaller isotopic fractionation, an increasing portion of the lower temperature (authigenic clay-associated) sink could contribute to the rise of the seawater Li isotope value. This effect would moderate the extent to which the isotopic value of continental inputs must have changed in order to explain the seawater record over the Cenozoic. Nonetheless, unless the magnitude of fractionation during removal differs significantly from current understanding, substantial change in the δLi7 of inputs from continental weathering must have occurred. Our modeling suggests that dissolved riverine fluxes in the early Eocene were characterized by δLi7 of ~0 to +13‰, with best estimates of 6.6-12.6‰; these values imply increases over the past 60 Myrs of between 10 and 24‰, and we view a ~13‰ increase as a likely scenario. These changes would have been accompanied by increases in both the dissolved Li flux from continental weathering and the removal flux from seawater into marine authigenic clays. Increases in δLi7 of continental input are consistent with a change in the global denudation regime as a result of increasing continental erosion rate through the Cenozoic. Changes in denudation may have meant increasing climate sensitivity of weathering over time but do not require globally supply-limited and thus entirely climate-insensitive weathering in the early Cenozoic. © 2014 Elsevier B.V.


Stohl W.,University of Southern California | Hilbert D.M.,Zyngenia
Nature Biotechnology | Year: 2012

For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab (Benlysta), is a human monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). The approval of belimumab combined a pioneering approach to genomics-based gene discovery, an astute appreciation of translational medicine, a disciplined clinical strategy, a willingness to take calculated risks, a devoted cadre of patients and physicians and a healthy dose of serendipity. Collectively, these efforts have provided a model for the development of a new generation of drugs to treat the broad manifestations of SLE. However, as a substantial percentage of SLE patients do not respond to belimumab, further research is needed to better characterize the pathogenetic mechanisms of SLE, identify additional therapeutic targets, and develop effective and nontoxic novel agents against these targets. © 2012 Nature America, Inc. All rights reserved.


Feakins S.J.,University of Southern California
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2013

Plant leaf wax hydrogen isotope (δDwax) reconstructions are increasingly being used to reconstruct hydrological change. This approach is based upon the assumption that variations in hydroclimatic variables, and in particular, the isotopic composition of precipitation (δDP), dominate δDwax. However modern calibration studies suggest that offsets between plant types may bias the δDwax hydrological proxy at times of vegetation change. In this study, I pair leaf wax analyses with published pollen data to quantify this effect and construct the first vegetation-corrected hydrogen isotopic evidence for precipitation (δDcorrP). In marine sediments from Deep Sea Drilling Program Site 231 in the Gulf of Aden spanning 11.4-3.8Ma (late Miocene and earliest Pliocene), I find 77δ swings in δDwax that correspond to pollen evidence for substantial vegetation change. Similarities between δDP and δDcorrP imply that the hydrological tracer is qualitatively robust to vegetation change. However, computed vegetation corrections can be as large as 31δ indicating substantial quantitative uncertainty in the raw hydrological proxy. The resulting δDcorrP values quantify hydrological change and allow us to identify times considerably wetter than modern at 11.09, 7.26, 5.71 and 3.89Ma. More generally, this novel interpretative framework builds the foundations of improved quantitative paleohydrological reconstructions with the δDwax proxy, in contexts where vegetation change may bias the plant-based proxy. The vegetation corrected paleoprecipitation reconstruction δDcorrP, represents the best available estimate as proof-of-concept, for an approach that I hope will be refined and more broadly applied. © 2013 Elsevier B.V.


Jagadish K.,University of Southern California
Biopolymers | Year: 2010

Cyclotides are a new emerging family of large plant-derived backbone-cyclized polypeptides (approximately 30 amino acids long) that share a disulfide-stabilized core (three disulfide bonds) characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds make them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently, more than 100 sequences of different cyclotides have been characterized, and the number is expected to increase dramatically in the coming years. Considering their stability and biological activities like anti-HIV, uterotonic, and insecticidal, and also their abilities to cross the cell membrane, cyclotides can be exploited to develop new stable peptide-based drugs. We have recently demonstrated the intriguing possibility of producing libraries of cyclotides inside living bacterial cells. This opens the possibility to generate large genetically encoded libraries of cyclotides that can then be screened inside the cell for selecting particular biological activities in a high-throughput fashion. The present minireview reports the efforts carried out toward the selection of cyclotide-based compounds with specific biological activities for drug design.


Ginsburg P.B.,University of Southern California
Health Affairs | Year: 2014

The ongoing consolidation between and among hospitals and physicians tends to raise prices for health care services, which poses increasing challenges for private purchasers and payers. This article examines strategies that these purchasers and payers can pursue to combat provider leverage to increase prices. It also examines opportunities for governments to either support or constrain these strategies. In response to higher prices, payers are developing new approaches to benefit and network design, some of which may be effective in moderating prices and, in some cases, volume. These approaches interact with public policy because regulation can either facilitate or constrain them. Federal and state governments also have opportunities to limit consolidation's effect on prices by developing antitrust policies that better address current market environments and by fostering the development of physician organizations that can increase competition and contract with payers under shared-savings approaches. The success of these private- and public-sector initiatives likely will determine whether governments shift from supporting competition to directly regulating payment rates. © 2014 Project HOPE-The People-to-People Health Foundation, Inc.


Wittig C.,University of Southern California
Physical Chemistry Chemical Physics | Year: 2012

Geometric phase is an interesting topic that is germane to numerous and varied research areas: molecules, optics, quantum computing, quantum Hall effect, graphene, and so on. It exists only when the system of interest interacts with something it perceives as exterior. An isolated system cannot display geometric phase. This article addresses geometric phase in polyatomic molecules from a gauge field theory perspective. Gauge field theory was introduced in electrodynamics by Fock and examined assiduously by Weyl. It yields the gauge field A μ, particle-field couplings, and the Aharonov-Bohm phase, while Yang-Mills theory, the cornerstone of the standard model of physics, is a template for non-Abelian gauge symmetries. Electronic structure theory, including nonadiabaticity, is a non-Abelian gauge field theory with matrix-valued covariant derivative. Because the wave function of an isolated molecule must be single-valued, its global U(1) symmetry cannot be gauged, i.e., products of nuclear and electron functions such as χ nψ n are forbidden from undergoing local phase transformation on R, where R denotes nuclear degrees of freedom. On the other hand, the synchronous transformations (first noted by Mead and Truhlar): ψ n → ψ ne iζ and simultaneously χ n → χ ne -iζ, preserve single-valuedness and enable wave functions in each subspace to undergo phase transformation on R. Thus, each subspace is compatible with a U(1) gauge field theory. The central mathematical object is Berry's adiabatic connection i〈n∇n〉, which serves as a communication link between the two subsystems. It is shown that additions to the connection according to the gauge principle are, in fact, manifestations of the synchronous (e iζ/ e -iζ) nature of the ψ n and χ n phase transformations. Two important U(1) connections are reviewed: qA μ from electrodynamics and Berry's connection. The gauging of SU(2) and SU(3) is reviewed and then used with molecules. The largest gauge group applicable in the immediate vicinity of a two-state intersection is U(2), which factors to U(1) × SU(2). Gauging SU(2) yields three fields, whereas U(1) is not gauged, as the result cannot be brought into registry with electronic structure theory, and there are other problems as well. A parallel with spontaneous symmetry breaking in electroweak theory is noted. Loss of SU(2) symmetry as the energy gap between adiabats increases yields the inter-related U(1) symmetries of the upper and lower adiabats, with spinor character imprinted in the vicinity of the degeneracy. © the Owner Societies 2012.


Raza H.,University of Southern California