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Boston, MA, United States

Boston University is a private research university located in Boston, Massachusetts. The university is nonsectarian, but is historically affiliated with the United Methodist Church.The university has more than 3,800 faculty members and 33,000 students, and is one of Boston's largest employers. It offers bachelor's degrees, master's degrees, and doctorates, and medical, dental, business, and law degrees through eighteen schools and colleges on two urban campuses. The main campus is situated along the Charles River in Boston's Fenway-Kenmore and Allston neighborhoods, while the Boston University Medical Campus is in Boston's South End neighborhood. BU also operates 75 study abroad programs in more than 33 cities in over twenty countries and has internship opportunities in ten different countries .BU is categorized as an RU/VH Research University in the Carnegie Classification of Institutions of Higher Education. BU is a member of the Boston Consortium for Higher Education and the Association of American Universities.The university counts seven Nobel Laureates including Martin Luther King, Jr. and Elie Wiesel, 35 Pulitzer Prize winners, nine Academy Award winners, Emmy and Tony Award winners among its faculty and alumni. BU also has MacArthur, Sloan, and Guggenheim Fellowship holders as well as American Academy of Arts and science and National Academy of science members among its past and present graduates and faculty.The Boston University Terriers compete in the NCAA's Division I. BU athletic teams compete in the Patriot League, and Hockey East conferences, and their mascot is Rhett the Boston Terrier. Boston University is well known for men's hockey, in which it has won five national championships, most recently in 2009. In 2014, Boston University ranked #100 among all colleges in the United States by average SAT score. Wikipedia.


Sandvik A.W.,Boston University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

Various lattice geometries and boundary conditions are used to investigate valence-bond-solid (VBS) ordering in the ground state of an S=1/2 square-lattice quantum spin model-the J-Q model, in which four- or six-spin interactions Q are added to the standard Heisenberg exchange J. Ground-state results for finite systems (with up to thousands of spins) are obtained using an unbiased projector quantum Monte Carlo method. It is found that great care has to be taken when extrapolating the order parameter to infinite lattice size, in particular, in cylinder geometry. Even though strong VBS order exists in two dimensions, and is established clearly with increasing system size on L×L lattices (or L x×L y lattices with a fixed aspect ratio L x/L y of order 1), only short-range VBS correlations are observed on long cylinders (when L x→∞ at fixed L y). The correlation length increases with the cylinder width, until long-range order sets in at a "critical" width. This width is very large even when the 2D order is relatively strong. For example, for a system in which the order parameter is 70% of the largest possible value, L y=8 is required for ordering. Extrapolations of the VBS order parameter based on correlation functions (the square of the order parameter) for small L×L lattices can also be misleading. For a 20%-ordered system, results for L up to ≈20 appear to extrapolate clearly to a vanishing order parameter, while for larger lattices the scaling behavior crosses over and extrapolates to a nonzero value (with exponentially small finite-size corrections). The VBS order parameter also exhibits interesting edge effects related the known emergent U(1) symmetry close to a "deconfined" critical point, which, if not considered properly, can lead to wrong conclusions for the thermodynamic limit. The observed finite-size behavior for small L×L lattices and long cylinders is very similar to that predicted for a Z 2 spin liquid. The results therefore raise concerns about recent numerical work claiming Z 2 spin-liquid ground states in 2D frustrated quantum spin systems, in particular, the Heisenberg model with nearest and next-nearest-neighbor couplings. Based on the results presented so far, a VBS state in this system cannot be ruled out. © 2012 American Physical Society.


The antiferromagnetic to valence-bond-solid phase transition in the two-dimensional J-Q model (an S=1/2 Heisenberg model with four-spin interactions) is studied using large-scale quantum Monte Carlo simulations. The results support a continuous transition of the ground state, in agreement with the theory of "deconfined" quantum criticality. There are, however, large corrections to scaling, of logarithmic or very slowly decaying power-law form, which had not been anticipated. This suggests that either the SU(N) symmetric noncompact CPN-1 field theory for deconfined quantum criticality has to be revised or that the theory for N=2 (as in the system studied here) differs significantly from N→∞ (where the field theory is analytically tractable). © 2010 The American Physical Society.


We investigate the ionospheric conditions required to explain Mars Express Mars Advanced Radar for Subsurface and Ionosphere Sounding topside radar sounder observations of ionospheric attenuation in excess of 13 dB at 5 MHz during solar energetic particle events. We develop theoretical expressions for the attenuation caused by a layer of ionospheric plasma in cases of high, intermediate, and low radio frequency relative to the electron-neutral collision frequency at the ionospheric layer. We apply these relationships to four layers: the M2 layer produced at 120 km by solar extreme ultraviolet photons, the M1 layer produced at 100 km by solar X-ray photons and associated electron impact ionization, the meteoric layer produced at 85 km by meteoroid ablation, and a putative plasma layer produced at 35 km by cosmic rays. Attenuation is weaker in the M2 layer than in the M1 layer. Attenuation in the M1 and meteoric layers are comparable, although their properties are quite variable. The greatest attenuation for radio frequencies above 50 MHz occurs in the predicted plasma layer at 35 km, but its effects are relatively small at lower frequencies. If optimally located with a peak altitude of 50 km, a layer with a peak plasma density of 109 m-3 is sufficient to explain the observed 13 dB attenuation. Although the electron densities produced by solar energetic particle events at Mars have not been directly simulated, the required electron densities are plausible. However, the altitude at which solar energetic particles produce plasma is uncertain. Copyright 2011 by the American Geophysical Union.


Schneider T.M.,Harvard University | Gibson J.F.,Georgia Institute of Technology | Burke J.,Boston University
Physical Review Letters | Year: 2010

We demonstrate the existence of a large number of exact solutions of plane Couette flow, which share the topology of known periodic solutions but are localized in one spatial dimension. Solutions of different size are organized in a snakes-and-ladders structure strikingly similar to that observed for simpler pattern-forming partial differential equations. These new solutions are a step towards extending the dynamical systems view of transitional turbulence to spatially extended flows. © 2010 The American Physical Society.


Clarkin C.E.,University of Southampton | Gerstenfeld L.C.,Boston University
Cell Biochemistry and Function | Year: 2013

Vascular endothelial growth factor (VEGF) is an endothelial cell survival factor and is required for effective coupling of angiogenesis and osteogenesis. Although central to bone homeostasis, repair and the pathobiology that affect these processes, the precise mechanisms coupling endothelial cell function within bone formation and remodelling remain unclarified. This review will (i) focus on the potential directionality of VEGF signalling in adult bone by identifying the predominant source of VEGF within the bone microenvironment, (ii) will summarize current VEGF receptor expression studies by bone cells and (iii) will provide evidence for a role for VEGF signalling during postnatal repair and osteoporosis. A means of understanding the directionality of VEGF signalling in adult bone would allow us to most effectively target angiogenic pathways in diseases characterized by changes in bone remodelling rates and enhance bone repair when compromised. © 2012 John Wiley & Sons, Ltd.


Wasserman A.M.,Boston University
American Family Physician | Year: 2011

Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management. © 2011 American Academy of Family Physicians.


Carling P.,Boston University
American Journal of Infection Control | Year: 2013

The value of objectively monitoring and improving environmental cleaning in health care settings is becoming increasingly recognized as an important component of interventions to mitigate the transmission of health care-associated pathogens. Whereas the 2010 Centers for Disease Control and Prevention tool kit "Options for Evaluating Environmental Cleaning" provides detailed guidance related to implementing such programs, there is a need to clearly understand the value and limitations of various environmental cleaning monitoring approaches to ensure the favorable impact of such activities. Copyright © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.


Neogi T.,Boston University
Osteoarthritis and Cartilage | Year: 2013

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide, largely due to pain, the primary symptom of the disease. The pain experience in knee OA in particular is well-recognized as typically transitioning from intermittent weight-bearing pain to a more persistent, chronic pain. Methods to validly assess pain in OA studies have been developed to address the complex nature of the pain experience. The etiology of pain in OA is recognized to be multifactorial, with both intra-articular and extra-articular risk factors. Nonetheless, greater insights are needed into pain mechanisms in OA to enable rational mechanism-based management of pain. Consequences of pain related to OA contribute to a substantial socioeconomic burden. © 2013 Osteoarthritis Research Society International.


Neogi T.,Boston University
Therapeutic Advances in Musculoskeletal Disease | Year: 2012

Osteoarthritis (OA), the most common form of arthritis, is now understood to involve all joint tissues, with active anabolic and catabolic processes. Knee OA in particular is considered to be a largely mechanically-driven disease. As bone adapts to loads by remodeling to meet its mechanical demands, bone alterations likely play an important role in OA development. Subchondral bone changes in bone turnover, mineralization, and volume result in altered apparent and material density of bone that may adversely affect the joint's biomechanical environment. Subchondral bone alterations such as bone marrow lesions (BMLs) and subchondral bone attrition (SBA) both tend to occur more frequently in the more loaded knee compartments, and are associated with cartilage loss in the same region. Recently, MRI-based 3D bone shape has been shown to track concurrently with and predict OA onset.The contributions of structural abnormalities to the clinical manifestations of knee OA are becoming better understood as well. While a structure-symptom discordance in knee OA is thought to exist, such observations do not take into account all potential factors that can contribute to between-person differences in the pain experience. Using novel methodology, pain fluctuation has been associated with changes in BMLs, synovitis and effusion. SBA has also been associated with knee pain, but the relationship of osteophytes to pain has been conflicting.Understanding the pathophysiologic sequences and consequences of OA pathology will guide rational therapeutic targeting. Importantly, rational treatment targets require understanding what structures contribute to pain as pain is the reason patients seek medical care. © The Author(s), 2012.


Rosen A.K.,Boston University
Medical care research and review : MCRR | Year: 2010

Strengthening safety climate is recognized as a necessary strategy for improving patient safety. Yet there is little empirical evidence linking hospitals' safety climate with safety outcomes.The authors explored the potential relationship between safety climate and Veterans Health Administration hospital safety performance using the Patient Safety Indicator (PSI) rates. Safety climate survey data were merged with hospital discharge data to calculate PSIs. Linear regressions examined the relationship between hospitals' safety climate and dimensions of safety climate with individual PSIs and a PSI composite measure, controlling for organizational-level variables. Safety climate overall was not related to the PSIs or to the PSI composite, although a few individual dimensions of safety climate were associated with specific PSIs. Perceptions of frontline staff were more closely aligned with PSIs than those of senior managers.


Isaacson S.A.,Boston University
Journal of Chemical Physics | Year: 2013

The reaction-diffusion master equation (RDME) is a lattice stochastic reaction-diffusion model that has been used to study spatially distributed cellular processes. The RDME is often interpreted as an approximation to spatially continuous models in which molecules move by Brownian motion and react by one of several mechanisms when sufficiently close. In the limit that the lattice spacing approaches zero, in two or more dimensions, the RDME has been shown to lose bimolecular reactions. The RDME is therefore not a convergent approximation to any spatially continuous model that incorporates bimolecular reactions. In this work we derive a new convergent RDME (CRDME) by finite volume discretization of a spatially continuous stochastic reaction-diffusion model popularized by Doi. We demonstrate the numerical convergence of reaction time statistics associated with the CRDME. For sufficiently large lattice spacings or slow bimolecular reaction rates, we also show that the reaction time statistics of the CRDME may be approximated by those from the RDME. The original RDME may therefore be interpreted as an approximation to the CRDME in several asymptotic limits. © 2013 AIP Publishing LLC.


Carvalho L.,Boston University
Journal of Statistical Software | Year: 2015

We propose a new algorithm for computing extreme probabilities of Kolmogorov's goodness-of-fit measure, Dn. This algorithm is an improved version of the method orig- inally proposed by Wang, Tsang, and Marsaglia (2003) based on a result from Durbin (1973). The new algorithm keeps the same numerical precision of the Wang et al. (2003) method, but is more efficient: it features linear instead of quadratic space complexity and has better time complexity for a common range of input parameters of practical impor- tance. The proposed method is implemented in the R package kolmim, which also includes an improved routine to perform one-sample two-sided exact Kolmogorov-Smirnov tests. © 2015, Journal of Statistical Software. All right reserved.


Bernstein A.S.,Boston University
Annual Review of Public Health | Year: 2014

In the wake of a species extinction event unprecedented in human history, how the variety, distribution, and abundance of life on earth may influence health has gained credence as a worthy subject for research and study at schools of public health and for consideration among policy makers. This article reviews a few of the principal ways in which health depends on biodiversity, including the discovery of new medicines, biomedical research, the provision of food, and the distribution and spread of infections. It also examines how changes in biological diversity underlie much of the global burden of disease and how a more thorough understanding of life on earth and its relationships has the potential to greatly alleviate and prevent human suffering. ©2014 by Annual Reviews. All rights reserved.


Wong W.S.,Chinese University of Hong Kong | Baillieul J.,Boston University
IEEE Transactions on Automatic Control | Year: 2012

Recent papers have treated control communication complexity in the context of information-based, multiple agent control systems including nonlinear systems of the type that have been studied in connection with quantum information processing. The present paper continues this line of investigation into a class of two-agent distributed control systems in which the agents cooperate in order to realize common goals that are determined via independent actions undertaken individually by the agents. A basic assumption is that the actions taken are unknown in advance to the other agent. These goals can be conveniently summarized in the form of a target matrix, whose entries are computed by the control system responding to the choices of inputs made by the two agents. We show how to realize such target matrices for a broad class of systems that possess an input-output mapping that is bilinear. One can classify control-communication strategies, known as control protocols, according to the amount of information sharing occurring between the two agents. Protocols that assume no information sharing on the inputs that each agent selects and protocols that allow sufficient information sharing for identifying the common goals are the two extreme cases. Control protocols will also be evaluated and compared in terms of cost functionals given by integrated quadratic functions of the control inputs. The minimal control cost of the two classes of control protocols are analyzed and compared. The difference in the control costs between the two classes reflects an inherent trade-off between communication complexity and control cost. © 2012 IEEE.


Wang Y.C.,Columbia University | McPherson K.,University of Oxford | Marsh T.,National Heart Forum | Gortmaker S.L.,Boston University | Brown M.,National Heart Forum
The Lancet | Year: 2011

Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations - the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492 000-669 000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. © 2011 Elsevier Ltd.


Beck L.H.,Boston University
Seminars in Nephrology | Year: 2010

An association between the glomerular disease membranous nephropathy (MN) and malignancy has long been appreciated, but evidence supporting this relationship remains limited, speculative, and, at times, controversial. Reports that the two disease processes often evolve in parallel, as well as the occasional findings of tumor antigens or tumor-reactive antibodies within glomerular immune deposits, are all supportive of an association. However, the diagnosis of both MN and malignancy in the same individual also may be coincidental, especially in an older demographic group in which both diseases tend to occur. This article briefly reviews the proposed pathogenetic mechanisms of idiopathic and secondary forms of MN, as well as the arguments for and against the contention that malignancy-associated MN is itself a distinct clinical entity. In addition, the recent identification of the M-type phospholipase A 2 receptor as a major glomerular antigen in idiopathic MN has the potential to offer fresh tools that might help resolve some of the controversy, and ultimately aid in the decision of how aggressively to screen for malignancy in an individual diagnosed with MN. © 2010 Elsevier Inc.


Rosenquist J.N.,Harvard University | Murabito J.,Boston University | Fowler J.H.,University of California at San Diego | Christakis N.A.,Harvard University
Annals of Internal Medicine | Year: 2010

Background: Alcohol consumption has important health-related consequences and numerous biological and social determinants. Objective: To explore quantitatively whether alcohol consumption behavior spreads from person to person in a large social network of friends, coworkers, siblings, spouses, and neighbors, followed for 32 years. Design: Longitudinal network cohort study. Setting: The Framingham Heart Study. Participants: 12 067 persons assessed at several time points between 1971 and 2003. Measurements: Self-reported alcohol consumption (number of drinks per week on average over the past year and number of days drinking within the past week) and social network ties, measured at each time point. Results: Clusters of drinkers and abstainers were present in the network at all time points, and the clusters extended to 3 degrees of separation. These clusters were not only due to selective formation of social ties among drinkers but also seem to reflect interpersonal influence. Changes in the alcohol consumption behavior of a person's social network had a statistically significant effect on that person's subsequent alcohol consumption behavior. The behaviors of immediate neighbors and coworkers were not significantly associated with a person's drinking behavior, but the behavior of relatives and friends was. Limitations: A nonclinical measure of alcohol consumption was used. Also, it is unclear whether the effects on long-term health are positive or negative, because alcohol has been shown to be both harmful and protective. Finally, not all network ties were observed. Conclusion: Network phenomena seem to influence alcohol consumption behavior. This has implications for clinical and public health interventions and further supports group-level interventions to reduce problematic drinking. © 2010 American College of Physicians.


Mazumdar V.,Boston University
PloS one | Year: 2013

Microbial biofilms are often composed of multiple bacterial species that accumulate by adhering to a surface and to each other. Biofilms can be resistant to antibiotics and physical stresses, posing unresolved challenges in the fight against infectious diseases. It has been suggested that early colonizers of certain biofilms could cause local environmental changes, favoring the aggregation of subsequent organisms. Here we ask whether the enzyme content of different microbes in a well-characterized dental biofilm can be used to predict their order of colonization. We define a metabolic distance between different species, based on the overlap in their enzyme content. We next use this metric to quantify the average metabolic distance between neighboring organisms in the biofilm. We find that this distance is significantly smaller than the one observed for a random choice of prokaryotes, probably reflecting the environmental constraints on metabolic function of the community. More surprisingly, this metabolic metric is able to discriminate between observed and randomized orders of colonization of the biofilm, with the observed orders displaying smaller metabolic distance than randomized ones. By complementing these results with the analysis of individual vs. joint metabolic networks, we find that the tendency towards minimal metabolic distance may be counter-balanced by a propensity to pair organisms with maximal joint potential for synergistic interactions. The trade-off between these two tendencies may create a "sweet spot" of optimal inter-organism distance, with possible broad implications for our understanding of microbial community organization.


Lafyatis R.,Boston University
Current Rheumatology Reports | Year: 2012

Important clinical advances in the treatment of systemic sclerosis have been made, yet fibrotic disease remains largely untreatable. Optimal design of clinical trials to test new therapeutics for fibrotic disease features has suffered from dual difficulties in patient selection and patient evaluation. Patient selection for entry into trials for treatment of interstitial lung disease and/or skin fibrosis is challenged by the natural history of the disease, which stabilizes in some patients while relentlessly progressing in others, and our lack of good clinical markers to distinguish between these trajectories. Patient evaluation is made difficult, particularly in skin disease, by the inherent difficulty in quantifying the extent of disease. Biomarkers hold the potential to solve many of these problems as surrogate outcome measures and as markers for disease progression. Identified biomarkers may have the potential to graduate to surrogate outcome singly or, more likely, in combination. Predictive biomarkers are still largely unknown. © 2011 Springer Science+Business Media, LLC.


Dickerson B.C.,Biomedical Imaging Center | Eichenbaum H.,Boston University
Neuropsychopharmacology | Year: 2010

The ability to encode and retrieve our daily personal experiences, called episodic memory, is supported by the circuitry of the medial temporal lobe (MTL), including the hippocampus, which interacts extensively with a number of specific distributed cortical and subcortical structures. In both animals and humans, evidence from anatomical, neuropsychological, and physiological studies indicates that cortical components of this system have key functions in several aspects of perception and cognition, whereas the MTL structures mediate the organization and persistence of the network of memories whose details are stored in those cortical areas. Structures within the MTL, and particularly the hippocampus, have distinct functions in combining information from multiple cortical streams, supporting our ability to encode and retrieve details of events that compose episodic memories. Conversely, selective damage in the hippocampus, MTL, and other structures of the large-scale memory system, or deterioration of these areas in several diseases and disorders, compromises episodic memory. A growing body of evidence is converging on a functional organization of the cortical, subcortical, and MTL structures that support the fundamental features of episodic memory in humans and animals. © 2010 Nature Publishing Group All rights reserved.


McGeeney B.E.,Boston University
Headache | Year: 2012

Most hallucinogens and cannabinoids fall into Federal Controlled Substances schedule 1, meaning they cannot be prescribed by practitioners, allegedly have no accepted medical use, and have a high abuse potential. The legal and regulatory status has inhibited clinical research on these substances such that there are no blinded studies from which to assess true efficacy. Despite such classification, hallucinogens and cannabinoids are used by patients with headache on occasion. Cannabinoids in particular have a long history of use for headache and migraine before prohibition and are still used by patients as a migraine abortive. Hallucinogens are being increasing used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and to maintain quiescence for which there is considerable anecdotal success. © 2012 American Headache Society.


Mez J.,Boston University
Current neurology and neuroscience reports | Year: 2013

Chronic traumatic encephalopathy (CTE, previously called punch drunk and dementia pugilistica) has a rich history in the medical literature in association with boxing, but has only recently been recognized with other contact sports, such as football and ice hockey, as well as with military blast injuries. CTE is thought to be a neurodegenerative disease associated with repeated concussive and subconcussive blows to the head. There is characteristic gross and microscopic pathology found in the brain, including frontal and temporal atrophy, axonal degeneration, and hyperphosphorylated tau and TAR DNA-binding protein 43 pathology. Clinically, there are characteristic progressive deficits in cognition (memory, executive dysfunction), behavior (explosivity, aggression), mood (depression, suicidality), and motor function (parkinsonism), which correlate with the anatomic distribution of brain pathology. While CTE shares clinical and neuropathological traits with other neurodegenerative diseases, the clinical syndrome and the neuropathology as a whole are distinct from other neurodegenerative diseases. Here we review the CTE literature to date. We also draw on the literature from mild traumatic brain injury and other neurodegenerative dementias, particularly when these studies provide guidance for future CTE research. We conclude by suggesting seven essential areas for future CTE research.


Culpepper L.,Boston University
Current Psychiatry Reports | Year: 2012

2012 marks one decade since the US Preventive Services Task Force recommended screening for depression. Advances since then include expanded understanding of the mechanisms underlying and influences of psychiatric disease on the development, course and outcomes of medical conditions. They also include collaborative care strategies to improve outcomes. However, the impact of such single disease approaches has been disappointing. Strategies that integrate management of multiple morbidities into primary care practice have greatly improved outcomes. Depression has been the only psychiatric condition incorporated into these strategies. Their expansion to integrate recognition and care of bipolar disease, anxiety disorders including PTSD, and substance abuse could further improve outcomes with modest marginal cost. Development of a screening and treatment monitoring instrument for multiple common psychiatric conditions is a prerequisite. One recently developed instrument, the M3, has the performance characteristics desirable, and provides opportunity to incorporate multiple common psychiatric conditions into multimorbidity integrated management. © Springer Science+Business Media, LLC 2012.


Safer J.D.,Boston University
Journal of Thyroid Research | Year: 2013

Although thyroid hormone is one of the most potent stimulators of growth and metabolic rate, the potential to use thyroid hormone to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated intriguing therapeutic potential for topical thyroid hormone. Topical T3 has accelerated wound healing and hair growth in rodents. Topical T4 has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along with skin manifestations of thyroid disease. The paper is intended to provide a context for recent findings of direct thyroid hormone action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing. © 2013 Joshua D. Safer.


Saudino K.J.,Boston University
Child Development | Year: 2012

Actigraphs and parent and observer ratings were used to explore genetic influences on continuity and change in activity level (AL) in early childhood. Over 300 pairs of twins wore actigraphs for a 48-hr period in the home and laboratory at ages 2 and 3. AL was genetically influenced at both ages with little evidence of differential heritability across age. For all measures, genetic influences contributed to phenotypic continuity. With the exception of the actigraph measure of AL in the home, new genetic effects emerged at age 3 indicating that genetic factors influence both continuity and change in AL in early childhood. Nonshared environmental influences were also a source of change in AL across the transition from infancy to early childhood. © 2011 The Author. Child Development © 2011 Society for Research in Child Development, Inc.


Li X.,Boston University
The Journal of bone and joint surgery. American volume | Year: 2013

Obesity is increasingly prevalent in the United States. There are several reports of outcomes in obese patients after total knee or hip replacement. The purpose of this study was to compare the functional outcomes and complications of obese patients undergoing shoulder arthroplasty with those of overweight or normal-weight patients. Seventy-six patients who underwent primary total shoulder arthroplasty were grouped according to body mass index. The groups were classified as: normal, which was denoted by a body mass index of <25 kg/m2 (twenty-six patients); overweight, which was denoted by a body mass index of 25 to 29.9 kg/m2 (twenty-five patients); and obese, which was denoted by a body mass index of ≥30 kg/m2 (twenty-five patients). Preoperative demographics and perioperative and postoperative complications were recorded. The American Shoulder and Elbow Surgeons score, Short Form-36, and visual analog scale pain and fatigue scores were evaluated at baseline and at the two-year follow-up visit. In the normal group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 38.4 ± 15.5 points preoperatively to 80.2 ± 19.4 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 38.3 ± 6.5 points preoperatively to 53.7 ± 11.3 points at two years postoperatively (p < 0.001); the visual analog scale pain scores decreased from a mean score of 62 points preoperatively to 12 points at two years postoperatively (p < 0.001). In the overweight group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 37.4 ± 18.1 points preoperatively to 75.2 ± 24.9 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 36.1 ± 8.0 points preoperatively to 39.8 ± 12.2 points at two years postoperatively (p = 0.21); the visual analog scale pain scores decreased from 68 points to 18 points (p < 0.001). In the obese group, the mean scores (and standard deviation) improved for the American Shoulder and Elbow Surgeons score from 35.8 ± 12.5 points preoperatively to 80.0 ± 20.6 points at two years postoperatively (p < 0.001) and for the Short Form-36 Physical Component Summary score from 36.3 ± 8.4 points preoperatively to 40.7 ± 12.4 points at two years postoperatively (p = 0.15); the visual analog scale pain scores decreased from 66 points preoperatively to 11 points at two years postoperatively (p < 0.001). There was one deep infection in the overweight group that required surgical irrigation and debridement. Two revisions of the components were required in the normal group. Obesity did not have a detrimental effect on the improvement of short-term shoulder function. However, the overall physical function of obese and overweight patients does not significantly improve after total shoulder arthroplasty. In the normal body mass index group, patients did improve overall physical function after total shoulder arthroplasty. Prognostic level II. See Instructions for Authors for a complete description of levels of evidence.


Nguyen H.T.,Boston University | Pearce J.M.,Michigan Technological University
Solar Energy | Year: 2012

Recently several algorithms have been developed to calculate the solar photovoltaic (PV) potential on the basis of 2.5D raster data that can capture urban morphology. This study provides a new algorithm that (i) incorporates both terrain and near surface shadowing effects on the beam component; (ii) scales down the diffuse components of global irradiation; and (iii) utilizes free and open source GRASS and the module r. sun in modeling irradiation. This algorithm is semi-automatic and easy to upgrade or correct (no hand drawn areas), open source, detailed and provides rules of thumb for PV system design at the municipal level. The workflow is pilot tested on LiDAR data for 100 buildings in downtown Kingston, Ontario. Shading behavior was considered and suitable roof sections for solar PV installations selected using a multi-criteria objective. At sub-meter resolution and small time steps the effect of occlusion from near object was determined. Annual daily horizontal irradiation values were refined at 0.55. m resolution and were shown to be lower than those obtained at 90. m by 30%. The robustness of r. sun as capable of working with different levels of surface complexity has been confirmed. Finally, the trade off of each computation option (spatial resolution, time step and shading effect) has been quantified at the meso scale, to assist planners in developing the appropriate computation protocols for their regions. © 2012 Elsevier Ltd.


Huang G.T.-J.,Boston University
Frontiers in Bioscience - Elite | Year: 2011

Hard tissue is difficult to repair especially dental structures. Tooth enamel is incapable of self-repairing whereas dentin and cememtum can regenerate with limited capacity. Enamel and dentin are commonly under the attack by caries. Extensive forms of caries destroy enamel and dentin and can lead to dental pulp infection. Entire pulp amputation followed by the pulp space disinfection and filled with an artificial rubber-like material is employed to treat the infection - commonly known as root canal or endodontic therapy. Regeneration of dentin relies on having vital pulps; however, regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. With the advent of modern tissue engineering concept and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the recent endeavor on pulp and dentin tissue engineering and regeneration. The prospective outcome of the current advancement and challenge in this line of research will be discussed.


Cheston C.C.,Boston University | Flickinger T.E.,Johns Hopkins University | Chisolm M.S.,Johns Hopkins University
Academic Medicine | Year: 2013

Purpose: The authors conducted a systematic review of the published literature on social media use in medical education to answer two questions: (1) How have interventions using social media tools affected outcomes of satisfaction, knowledge, attitudes, and skills for physicians and physicians-in-training? and (2) What challenges and opportunities specific to social media have educators encountered in implementing these interventions? Method: The authors searched the MEDLINE, CINAHL, ERIC, Embase, PsycINFO, ProQuest, Cochrane Library, Web of Science, and Scopus databases (from the start of each through September 12, 2011) using keywords related to social media and medical education. Two authors independently reviewed the search results to select peer-reviewed, English-language articles discussing social media use in educational interventions at any level of physician training. They assessed study quality using the Medical Education Research Study Quality Instrument. Results: Fourteen studies met inclusion criteria. Interventions using social media tools were associated with improved knowledge (e.g., exam scores), attitudes (e.g., empathy), and skills (e.g., reflective writing). The most commonly reported opportunities related to incorporating social media tools were promoting learner engagement (71% of studies), feedback (57%), and collaboration and professional development (both 36%). The most commonly cited challenges were technical issues (43%), variable learner participation (43%), and privacy/security concerns (29%). Studies were generally of low to moderate quality; there was only one randomized controlled trial. Conclusions: Social media use in medical education is an emerging field of scholarship that merits further investigation. Educators face challenges in adapting new technologies, but they also have opportunities for innovation. Copyright © 2013 Taylor and Francis Group, LLC.


Robasky K.,Harvard University | Robasky K.,Boston University | Bulyk M.L.,Harvard University | Bulyk M.L.,Harvard-MIT Division of Health Sciences and Technology
Nucleic Acids Research | Year: 2011

The Universal PBM Resource for Oligonucleotide- Binding Evaluation (UniPROBE) database is a centralized repository of information on the DNAbinding preferences of proteins as determined by universal protein-binding microarray (PBM) technology. Each entry for a protein (or protein complex) in UniPROBE provides the quantitative preferences for all possible nucleotide sequence variants ('words') of length k ('k-mers'), as well as position weight matrix (PWM) and graphical sequence logo representations of the k-mer data. In this update, we describe >130% expansion of the database content, incorporation of a protein BLAST (blastp) tool for finding protein sequence matches in UniPROBE, the introduction of UniPROBE accession numbers and additional database enhancements. The UniPROBE database is available at http://uniprobe.org. © The Author(s) 2010.


Monach P.A.,Boston University
Current Treatment Options in Cardiovascular Medicine | Year: 2013

Opinion statement: Having diagnosed a patient as having IgG4-related disease, I would have a low threshold for recommending immune-suppressive treatment, and would make that recommendation for any patient with vascular involvement. My initial approach would be prednisone at 40-60 mg/day with a plan to reduce the dose every two weeks, e.g., 40, 30, 20, 15, 10, 7.5, 5, and 2.5 mg for 2 weeks each. In the event of relapse, I would double the current prednisone dose, slow the taper, and add azathioprine, anticipating using that drug for one year if the patient were to remain in remission. In the event or subsequent relapse, I would stop azathioprine and use rituximab. In a patient with large artery involvement, I would consult a vascular surgeon soon after diagnosis, anticipating a need for surgical repair. © 2013 Springer Science+Business Media New York.


Rosenzweig J.L.,Boston University
The American journal of managed care | Year: 2010

OBJECTIVE: To evaluate the effectiveness of a telephonic diabetes disease management intervention in a Medicare Advantage population with comorbid diabetes and coronary artery disease (CAD). STUDY DESIGN: Prospective unequal randomization design of 526 members from a Medicare Advantage segment of one region of a large national health plan from May 2005 through April 2007. METHODS: High-risk and high-cost patients with diabetes and CAD who were enrolled in telephonic diabetes disease management were compared with a randomly selected comparison group receiving usual care. Wilcoxon signed-rank tests were used to compare the groups on all-cause hospital admissions, diabetes-related hospital admissions, all-cause and diabetes-related emergency department (ED) visits, and all-cause medical costs. Changes in self-reported clinical outcomes also were measured in the intervention group. RESULTS: Patients receiving telephonic diabetes disease management had significantly decreased all-cause hospital admissions and diabetes-related hospital admissions (P <.05). The intervention group had decreased all-cause and diabetes-related ED visits, although the difference was not statistically significant. The comparison group had increased ED utilization. The intervention group decreased their all-cause total medical costs by $984.87 per member per year (PMPY) compared with a $4547.06 PMPY increase in the comparison group (P <.05). All clinical measures significantly improved (P <.05) in the intervention group. CONCLUSIONS: A disease management program for high-risk patients with diabetes and CAD was effective in reducing hospital inpatient admission and total costs in a Medicare Advantage population.


Marscher A.P.,Boston University
Astrophysical Journal | Year: 2014

The author presents a model for variability of the flux and polarization of blazars in which turbulent plasma flowing at a relativistic speed down a jet crosses a standing conical shock. The shock compresses the plasma and accelerates electrons to energies up to γmax ≳ 10 4 times their rest-mass energy, with the value of γmax determined by the direction of the magnetic field relative to the shock front. The turbulence is approximated in a computer code as many cells, each with a uniform magnetic field whose direction is selected randomly. The density of high-energy electrons in the plasma changes randomly with time in a manner consistent with the power spectral density of flux variations derived from observations of blazars. The variations in flux and polarization are therefore caused by continuous noise processes rather than by singular events such as explosive injection of energy at the base of the jet. Sample simulations illustrate the behavior of flux and linear polarization versus time that such a model produces. The variations in γ-ray flux generated by the code are often, but not always, correlated with those at lower frequencies, and many of the flares are sharply peaked. The mean degree of polarization of synchrotron radiation is higher and its timescale of variability shorter toward higher frequencies, while the polarization electric vector sometimes randomly executes apparent rotations. The slope of the spectral energy distribution exhibits sharper breaks than can arise solely from energy losses. All of these results correspond to properties observed in blazars. © 2014. The American Astronomical Society. All rights reserved.


Smith S.L.,University of Waterloo | Schwager M.,Boston University | Rus D.,Massachusetts Institute of Technology
IEEE Transactions on Robotics | Year: 2012

In this paper, we present controllers that enable mobile robots to persistently monitor or sweep a changing environment. The environment is modeled as a field that is defined over a finite set of locations. The field grows linearly at locations that are not within the range of a robot and decreases linearly at locations that are within range of a robot. We assume that the robots travel on given closed paths. The speed of each robot along its path is controlled to prevent the field from growing unbounded at any location. We consider the space of speed controllers that are parametrized by a finite set of basis functions. For a single robot, we develop a linear program that computes a speed controller in this space to keep the field bounded, if such a controller exists. Another linear program is derived to compute the speed controller that minimizes the maximum field value over the environment. We extend our linear program formulation to develop a multirobot controller that keeps the field bounded. We characterize, both theoretically and in simulation, the robustness of the controllers to modeling errors and to stochasticity in the environment. © 2012 IEEE.


Parshani R.,Bar - Ilan University | Buldyrev S.V.,Boston University | Buldyrev S.V.,Yeshiva University | Havlin S.,Bar - Ilan University
Physical Review Letters | Year: 2010

We study a system composed from two interdependent networks A and B, where a fraction of the nodes in network A depends on nodes of network B and a fraction of the nodes in network B depends on nodes of network A. Because of the coupling between the networks, when nodes in one network fail they cause dependent nodes in the other network to also fail. This invokes an iterative cascade of failures in both networks. When a critical fraction of nodes fail, the iterative process results in a percolation phase transition that completely fragments both networks. We show both analytically and numerically that reducing the coupling between the networks leads to a change from a first order percolation phase transition to a second order percolation transition at a critical point. The scaling of the percolation order parameter near the critical point is characterized by the critical exponent β=1. © 2010 The American Physical Society.


Hasselmo M.E.,Boston University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Data show a relationship of cellular resonance and network oscillations in the entorhinal cortex to the spatial periodicity of grid cells. This paper presents a model that simulates the resonance and rebound spiking properties of entorhinal neurons to generate spatial periodicity dependent upon phasic input from medial septum. The model shows that a difference in spatial periodicity can result from a difference in neuronal resonance frequency that replicates data from several experiments. The model also demonstrates a functional role for the phenomenon of theta cycle skipping in the medial entorhinal cortex. © 2013 The Author(s) Published by the Royal Society. All rights reserved.


Peres N.M.R.,University of Minho | Ribeiro R.M.,University of Minho | Castro Neto A.H.,Boston University
Physical Review Letters | Year: 2010

We study the effect of electron-electron interactions in the optical conductivity of graphene under an applied gate and derive a generalization of Elliott's formula, commonly used for semiconductors, for the optical intensity. We show that excitonic resonances are responsible for several features of the experimentally measured midinfrared response of graphene such as the increase of the conductivity beyond the universal value above the Fermi blocked regime, the broadening of the absorption at the threshold, and the decrease of the optical conductivity at higher frequencies. © 2010 The American Physical Society.


Haynes B.F.,Duke University | Kelsoe G.,Duke University | Harrison S.C.,Howard Hughes Medical Institute | Kepler T.B.,Duke University | Kepler T.B.,Boston University
Nature Biotechnology | Year: 2012

Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do produce them after years of chronic HIV-1 infection have one or more unusual characteristics, including polyreactivity for host antigens, extensive somatic hypermutation and long, variable heavy-chain third complementarity-determining regions, factors that may limit their expression by host immunoregulatory mechanisms. The isolation of BnAbs from HIV-1g-infected subjects and the use of computationally derived clonal lineages as templates provide a new path for HIV-1 vaccine immunogen design. This approach, which should be applicable to many infectious agents, holds promise for the construction of vaccines that can drive B cells along rare but desirable maturation pathways. © 2012 Nature America, All Right Reserved.


Davidson S.M.,Boston University
Journal of Ambulatory Care Management | Year: 2013

Efforts to influence utilization of services to bring down spending and to improve quality of care have largely failed. A critical reason is that most attention has focused on dysfunctional financial incentives without considering other factors that also influence physicians' utilization decisions. In this article, after providing a framework for ideal physician-patient interactions, questions are also raised about other influences, including physicians' impulse to help patients, professional codes of ethics, the threat of malpractice claims, and the leadership of health care organizations. An Appendix contains a summary of the literature on these factors. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Culpepper L.,Boston University
The Journal of clinical psychiatry | Year: 2013

Several barriers can hinder the diagnosis of ADHD in college students, especially those with unrecognized symptoms, dysfunctional behavior, or psychiatric conditions. One specific barrier includes the misuse of prescription stimulants among college students, perhaps to improve academic performance or to self-treat undiagnosed ADHD symptoms. Because of the dangers, both medical and legal, that nonmedical stimulant use can cause, clinicians must recognize these undiagnosed students and initiate proper treatment. By establishing a therapeutic relationship with students, clinicians can provide education, monitoring, and treatment options that will help minimize misuse of prescriptions while giving students the support they need to successfully complete college. © Copyright 2013 Physicians Postgraduate Press, Inc.


Verfaellie M.,Boston University
Journal of the International Neuropsychological Society : JINS | Year: 2013

Postconcussion symptoms (PCS) and functional outcomes were evaluated in 91 OEF/OIF outpatient veterans with reported histories of blast-exposure, with the goal of evaluating (1) the association between these outcomes and a clinical diagnosis of mild traumatic brain injury (mTBI) with or without loss of consciousness (LOC); and (2) the influence of post-traumatic stress disorder (PTSD) and depression on PCS reporting and perceived functional limitations. Individuals who reported mTBI with LOC had greater PCS complaints than individuals who reported mTBI without LOC or individuals without mTBI. However, after adjusting for severity of PTSD and depression symptoms, this group difference disappeared. Functional limitations were particularly prominent in the psychosocial domain. Again, PTSD was significantly associated with functional outcomes, but the mTBI with LOC group had greater psychosocial limitations than the other two groups, even when PTSD and depression symptoms were taken into account. These findings highlight the role of mental health in both outcomes, but additionally point to the impact of mTBI with LOC on long-term psychosocial adjustment.


Rodima-Taylor D.,Boston University
Applied Geography | Year: 2012

In African communities, informal associations are becoming increasingly important in shaping and mediating local adaptation practices. The study suggests that the concept of social innovation is useful for analyzing climate adaptation in the multiscale institutional environments with complex vulnerability contexts. Small-scale local associations have a potential to facilitate collective experimentation and risk management, contributing to the resilience and sustainability of the social-ecological system. Ethnographic focus is on the informal associations of economic cooperation and dispute mediation of Kuria people of northwest Tanzania, and the ways these institutional forms facilitate resource management and the negotiation of difference under income diversification. Organizational features of the groups are examined that facilitate social innovation and alternative patterns of communication, effecting flexible and relational connections between scales. The study examines the features of the local institutions that have a potential to enhance local adaptive capacity, and discusses possible challenges to sustainable climate adaptation. © 2011 Elsevier Ltd.


Einhorn T.A.,Boston University
Science Translational Medicine | Year: 2010

The development of new technologies to enhance skeletal healing after fracture or surgery is an important goal of musculoskeletal regenerative medicine. Although the bone morphogenetic proteins have shown some efficacy in this area, there is a need for more effective and less expensive therapies for bone repair and regeneration. A recent report demonstrating that Wnt signaling could be used to stimulate bone healing may provide a new direction for designing anabolic therapies for the skeleton. The identification of human phenotypes demonstrating robust bone formation as a result of mutations in Wnt signaling provides a strong basis for pursuing this area of investigation.


Odell C.A.,Boston University
Current Opinion in Pediatrics | Year: 2010

Purpose of Review: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly important as a cause of skin and soft tissue infections (SSTIs), particularly abscesses, in patients seen in the emergency department setting. The antibiotic sensitivity profile of Staphylococcus aureus isolates from SSTIs has changed over time in many geographic locations. Whether antibiotics are needed in the management of skin abscesses, and, if so, when, is controversial. Recent Findings: A number of studies have looked at antibiotic therapy in conjunction with incision and drainage in managing abscesses. Factors evaluated were resolution of infection, need for change in antibiotic therapy, hospitalization after initial outpatient management, need for an additional drainage procedure, and recurrence of infection within 30 days after the initial incision and drainage procedure. For abscesses, clinical failure was associated with lack of adequate incision and drainage and not antibiotic use, regardless of the size of the abscess or the choice of antibiotic therapy. For other soft tissue infections, when antibiotic susceptibility data were available for the infection (impetigo or cellulitis with purulent drainage but no abscess), there was no difference in clinical resolution of MRSA infection even if the infecting organism was resistant to the antibiotic chosen for therapy. Summary: CA-MRSA has become an important cause of SSTIs. Current data suggest that most abscesses can be treated successfully with incision and drainage alone. Antibiotic choice is more crucial for management of cellulitis and should be guided by the prevalence of CA-MRSA in the community and its antibiotic susceptibility profile. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


The Framingham Heart Study, the longest-running prospective epidemiologic study in history, was initiated in 1948 in response to the rising toll of coronary heart disease and hypertension. During the ensuing decades, the study of other diseases, notably stroke and dementia, was added. In 1971, 5124 offspring of the original cohort of 5209 men and women were added, and a third generation of 4095 men and women were added in 2002. The 3-generation structure was used to relate a host of risk factors measured in mid and late life to the subsequent development of stroke, dementia, and cognitive decline. It has also facilitated studies of family occurrence of disease over generations particularly for genomic research. Dementia and Alzheimer disease research has proceeded from the determination of risk factors for at least moderately severe Alzheimer disease in the first generation to mild cognitive impairment and mild Alzheimer disease in the offspring and to studies of the third generation for detection of pre-mild cognitive impairment and indicators of cognitive decline in mid life. These research efforts have been facilitated by genome-wide association studies, biomarkers, and multiple measures of subclinical vascular disease. The tempo of decline has been documented by serial quantitative measures of brain structure on magnetic resonance imaging and cognitive performance by neuropsychological testing. Clinical correlation with systematic neuropathological examinations of more than 150 brains has provided important confirmation of cerebrovascular and brain tissue indices of disease. Identification of persons at heightened risk for stroke, mild cognitive impairment, Alzheimer disease, and cognitive decline years prior to disease onset may facilitate delay in disease onset and prevention.


Kotton D.N.,Boston University
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Research discoveries in the fields of stem cell biology and regenerative medicine are beginning to advance and refine our understanding of lung injury and repair. Although these emerging studies offer unprecedented opportunities to develop novel therapies for a variety of lung diseases, the quickening pace of work in this nascent field also makes it difficult to discern hope from hype when addressing the pleas of patients eager for clinical translation or when seeking information on the risk versus reward of participation in clinical trials. This perspective provides an overview of the latest advances in lung-related stem cell research and places the new discoveries in a historical context. Established, lineage-restricted epithelial progenitors of the conducting airways and gas-exchanging alveoli are briefly reviewed, and controversial, newly proposed tissue-specific candidate lung stem/progenitor cells with broader differentiation repertoire are introduced. Exogenous derivation of lung epithelia from embryonic stem cells or induced pluripotent stem cells is also presented as an alternative method for engineering lung tissue de novo in culture. Copyright © 2012 by the American Thoracic Society.


Howe M.S.,Boston University
Journal of Fluid Mechanics | Year: 2010

An analysis is made of the noise generated during the passage of quiescent temperature/entropy inhomogeneities through regions of rapidly accelerated mean flow. This is an important source of jet engine core noise. Bake et al. (J. Sound Vib., vol. 326, 2009, pp. 574-598) have used an entropy wave generator coupled with a converging-diverging nozzle to perform a series of canonical measurements of the sound produced when the inhomogeneity consists of a nominally uniform slug of hot gas. When flow separation and jet formation occur in the diffuser section of the nozzle, it is shown in this paper that the vortex sound generated by the jet is strongly correlated with the entropy noise produced by the slug and that the overall noise level is significantly reduced. Streamwise stretching of the hot slug during high subsonic acceleration into the nozzle and the consequent attenuation of the entropy gradient in the nozzle are shown to significantly decrease the effective rate at which indirect combustion noise increases with the Mach number. Numerical predictions indicate that this is responsible for the peak observed by Bake et al. in the entropy-generated sound pressure at a nozzle Mach number near 0.6. © 2010 Cambridge University Press.


Jiang J.-W.,Shanghai University | Park H.S.,Boston University
Applied Physics Letters | Year: 2014

We perform classic molecular dynamics simulations to comparatively investigate the mechanical properties of single-layer MoS2 and a graphene/MoS2/graphene heterostructure under uniaxial tension. We show that the lattice mismatch between MoS2 and graphene will lead to an spontaneous strain energy in the interface. The Young's modulus of the heterostructure is much larger than that of MoS2. While the stiffness is enhanced, the yield strain of the heterostructure is considerably smaller than the MoS2 due to lateral buckling of the outer graphene layers owning to the applied mechanical tension. © 2014 AIP Publishing LLC.


Weber H.C.,Boston University
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2015

Purpose of Review: To highlight the most recent advances regarding gastrointestinal peptides and their relation to chronic itch, with focus on gastrin-releasing peptide (GRP), substance P, and their respective receptors. Recent Findings: GRP and its high-affinity GRP receptor (GRPR) have been identified as key regulators in the spinal cord itch pathway and may be involved in the maintenance of chronic itch sensation. Several neuropeptides including GRP, neuromedin B, and substance P regulate itch signals in a cooperative or inhibitory manner on the spinal level. Small clinical studies show that neurokinin 1 receptor antagonists might be of benefit in the treatment of chronic itch. Summary: Chronic itch is a burdensome clinical problem, for which no specific treatment is available. Studies on the mechanisms of pruriceptive sensation and its signaling to the central nervous system (CNS) via the spinal cord have elucidated a number of peptides that are implicated in the regulation of itch-specific signaling pathways. Among those, GRP and its high-affinity GRP receptor have been proposed as key elements in the itch-specific neuronal pathways. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Zaia J.,Boston University
OMICS A Journal of Integrative Biology | Year: 2010

Glycosylation defines the adhesive properties of animal cell surfaces and the surrounding extracellular environments. Because cells respond to stimuli by altering glycan expression, glycan structures vary according to spatial location in tissue and temporal factors. These dynamic structural expression patterns, combined with the essential roles glycans play in physiology, drive the need for analytical methods for glycoconjugates. In addition, recombinant glycoprotein drug products represent a multibillion dollar market. Effective analytical methods are needed to speed the identification of new targets and the development of industrial glycoprotein products, both new and biosimilar. Mass spectrometry is an enabling technology in glycomics. This review summarizes mass spectrometry of glycoconjugate glycans. The intent is to summarize appropriate methods for glycans given their chemical properties as distinct from those of proteins, lipids, and small molecule metabolites. Special attention is given to the uses of mass spectral profiling for glycomics with respect to the N-linked, O-linked, ganglioside, and glycosaminoglycan compound classes. Next, the uses of tandem mass spectrometry of glycans are summarized. The review finishes with an update on mass spectral glycoproteomics. © 2010, Mary Ann Liebert, Inc.


Castillo J.J.,The Miriam Hospital | Dalia S.,Brown University | Pascual S.K.,Boston University
Blood | Year: 2010

The incidence of non-Hodgkin lymphoma (NHL) has increased steadily for the past few decades. Previous studies have suggested an association between blood transfusions and NHL. The main objective of this study was to evaluate this relationship with a meta-analysis of observational studies. A literature search was undertaken, looking for case-control and cohort studies evaluating the risk of developing NHL in persons who received allogeneic blood transfusions; 14 studies were included. Outcome was calculated and reported as relative risk (RR). Heterogeneity was assessed with Cochrane Q and I2 statistics. Dissemination bias was evaluated by funnel plot visualization and trim-and-fill analysis. Quality assessment was performed with the Newcastle-Ottawa scale. Our analysis showed a RR of developing NHL of 1.05 (95% CI, 0.89-1.25; P = .42) and 1.34 (95% CI, 1.15-1.55; P < .01) in case-control and cohort studies, respectively. When pooling all studies, RR was 1.2 (95% CI, 1.07-1.35; P < .01). In subset analysis, RR of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was 1.66 (95% CI, 1.08-2.56; P = .02). The RR of NHL was elevated in both men and women and in persons receiving transfusions either before or after 1992. Blood transfusions appear to increase the risk of developing NHL; however, the risk of CLL/SLL appears higher than for other NHL subtypes. © 2010 by The American Society of Hematology.


Primack R.B.,Boston University | Miller-Rushing A.J.,National Park Service
BioScience | Year: 2012

Historical records are an important resource for understanding the biological impacts of climate change. Such records include naturalists' journals, club and field station records, museum specimens, photographs, and scientific research. Finding records and overcoming their limitations are serious challenges to climate change research. In the present article, we describe efforts to locate data from Concord, Massachusetts, and provide a template that can he replicated in other locations. Analyses of diverse data sources, including observations made in the 1850s by Henry David Thoreau, indicate that climate change is affecting the phenology, presence, and abundance of species in Concord. Despite recent work on historical records, many sources of historical data are underutilized. Analyses of these data may provide insights into climate change impacts and techniques to manage them. Moreover, the results are useful for communicating local examples of changing climate conditions to the public. © 2012 by American Institute of Biological Sciences. All rights reserved.


Frank-Kamenetskii M.D.,Boston University | Prakash S.,University of Pune
Physics of Life Reviews | Year: 2014

A critical overview of the extensive literature on fluctuations in the DNA double helix is presented. Both theory and experiment are comprehensively reviewed and analyzed. Fluctuations, which open up the DNA double helix making bases accessible for hydrogen exchange and chemical modification, are the main focus of the review. Theoretical descriptions of the DNA fluctuations are discussed with special emphasis on most popular among them: the nonlinear-dynamic Peyrard-Bishop-Dauxois (PBD) model and the empirical two-state (or helix-coil) model. The experimental data on the issue are comprehensibly overviewed in the historical retrospective with main emphasis on the hydrogen exchange data and formaldehyde kinetics. The theoretical descriptions are critically evaluated from the viewpoint of their applicability to describe DNA in water environment and from the viewpoint of agreement of their predictions with the reliable experimental data. The presented analysis makes it possible to conclude that, while the two-state model is most adequate from theoretical viewpoint and its predictions, based on an empirical parametrization, agree with experimental data very well, the PBD model is inapplicable to DNA in water from theoretical viewpoint on one hand and it makes predictions totally incompatible with reliable experimental data on the other. In particular, it is argued that any oscillation movements of nucleotides, assumed by the PBD model, are severely damped in water, that no "bubbles", which the PBD model predicts, exist in reality in linear DNA well below the melting range and the lifetime of an open state in DNA is actually 5 orders of magnitude longer than the value predicted by the PBD model. © 2014 Elsevier B.V.


Leventhal J.M.,Yale University | Gaither J.R.,Yale University | Sege R.,Boston University
Pediatrics | Year: 2014

BACKGROUND AND OBJECTIVE: Despite recent national attention on deaths from firearms, little information exists about children and adolescents who are hospitalized for firearm injuries. The objective was to determine the national frequency of firearm-related hospitalizations in the United States in children, compare rates by cause and demographics, and describe hospitalized cases. METHODS: We used the 2009 Kids' Inpatient Database to identify hospitalizations from firearm-related injuries in young people <20 years of age; International Classification of Diseases, Ninth Revision, Clinical Modification, and external-cause-of injury codes were used to categorize the injuries and the causes as follows: assault, suicide attempt, unintentional, or undetermined. Incidences were calculated by using the weighted number of cases and the intercensal population. Risk ratios compared incidences. RESULTS: In 2009, 7391 (95% confidence interval [CI]: 6523-8259) hospitalizations were due to firearm-related injuries. The hospitalization rate was 8.87 (95% CI: 7.83-9.92) per 100 000 persons <20 years of age. Hospitalizations due to assaults were most frequent (n = 4559) and suicide attempts were least frequent (n = 270). Of all hospitalizations, 89.2% occurred in males; the hospitalization rate for males was 15.22 per 100 000 (95% CI: 13.41-17.03) and for females was 1.93 (95% CI: 1.66-2.20). The rate for black males was 44.77 (95% CI: 36.69-52.85), a rate more than 10 times that for white males. Rates were highest for those aged 15 to 19 years (27.94; 95% CI: 24.42-31.46). Deaths in the hospital occurred in 453 (6.1%); of those hospitalized after suicide attempts, 35.1% died. CONCLUSIONS: On average, 20 US children and adolescents were hospitalized each day in 2009 due to firearm injuries. Public health efforts are needed to reduce this common source of childhood injury. Copyright © 2014 by the American Academy of Pediatrics.


Hall P.S.,Boston University
Physics of the Earth and Planetary Interiors | Year: 2012

We use a 2-dimensional numerical geodynamic model to investigate the evolution of the mantle wedge at subduction zones over a period of 300. Myr following the onset of subduction. A variety of parameterizations of the overriding plate, as well as plate subduction rates and mantle potential temperatures, are considered systematically. The average temperature in the mantle wedge within 120. km of the trench is found to decrease substantially (up to ∼100 °C) over this period, with the most rapid cooling occurring during the first 100. Myr. The observed cooling is not spatially uniform, but rather is concentrated in the uppermost 50. km of the mantle wedge, immediately beneath the overriding plate. Temperatures in the mantle wedge in the vicinity of arc volcanism decrease by as much as >200 °C over the 300. Myr period. This decrease in temperature results in a decrease in the portion of mantle wedge beneath the arc in which hydrous melting can occur, impacting both the distribution of melting within the wedge and likely the composition of erupted melts. The observed variations in temperatures in the subarc portion of the mantle wedge with time are significantly larger than the changes in temperature resulting from inclusion of radiogenic heat production in the overriding plate or a zone of partial coupling between the slab and mantle. The results suggest that the mantle wedge is warmer than predicted by steady state thermal models, which may account in part for the differences between the petrologically determined pressure and temperature of equilibration for arc magmas and predictions of the thermal structure of the mantle wedge obtained from steady state thermal models. © 2012 Elsevier B.V.


Peters O.,London Mathematical Laboratory | Klein W.,Boston University
Physical Review Letters | Year: 2013

Geometric Brownian motion (GBM) is a model for systems as varied as financial instruments and populations. The statistical properties of GBM are complicated by nonergodicity, which can lead to ensemble averages exhibiting exponential growth while any individual trajectory collapses according to its time average. A common tactic for bringing time averages closer to ensemble averages is diversification. In this Letter, we study the effects of diversification using the concept of ergodicity breaking. © 2013 American Physical Society.


Studies of gene expression at the single cell level in live bacterial cells represent a new and fertile area of research providing real-time, spatially specified information that cannot be obtained by techniques relying on large cell populations. Before recently, most single-cell studies have been concerned with gene expression at the protein level and explored the spatiotemporal localization and dynamics of different bacterial proteins. However, to fully understand the complex process of gene expression, it is necessary to visualize and quantify RNA molecules in the cellular environment. The first studies analysing the kinetics of RNA transcription and the distribution of RNA in single bacterial cells in real time have recently been reported. Here, I discuss the methods allowing RNA detection in living bacterial cells, the results on RNA kinetics and RNA localization, and the challenges for future research in this area. © 2011 Blackwell Publishing Ltd.


Rahimi N.,Boston University
Molecular Cancer Therapeutics | Year: 2012

A strict physiological balance between endogenous proangiogenic and antiangiogenic factors controls endothelial cell functions, such that endothelial cell growth is normally restrained. However, in pathologic angiogenesis, a shift occurs in the balance of regulators, favoring endothelial growth. Much of the control of angiogenic events is instigated through hypoxia-induced VEGF expression. The ubiquitin-proteasome system (UPS) plays a central role in fine-tuning the functions of core proangiogenic proteins, including VEGF, VEGFR- 2, angiogenic signaling proteins (e.g., the PLCγ1 and PI3 kinase/AKT pathways), and other non-VEGF angiogenic pathways. The emerging mechanisms by which ubiquitin modification of angiogenic proteins control angiogenesis involve both proteolytic and nonproteolytic functions. Here, I review recent advances that link the UPS to regulation of angiogenesis and highlight the potential therapeutic value of the UPS in angiogenesis- associated diseases. ©2012 AACR.


Jasti R.,Boston University | Bertozzi C.R.,Howard Hughes Medical Institute
Chemical Physics Letters | Year: 2010

Carbon nanotubes (CNTs) have emerged as some of the most promising materials for the technologies of the future. One of the most significant limitations to furthering the understanding and application of these fascinating systems is the lack of atomic-level structural control in their syntheses. Current synthetic methods produce mixtures of structures with varying physical properties. In this Letter, we describe the potential advantages, recent advances, and challenges that lie ahead for the bottom-up organic synthesis of homogeneous carbon nanotubes with well-defined structures. © 2010 Elsevier B.V. All rights reserved.


Preston A.R.,University of Texas at Austin | Eichenbaum H.,Boston University
Current Biology | Year: 2013

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. © 2013 Elsevier Ltd.


Calderwood S.K.,Beth Israel Deaconess Medical Center | Gong J.,Boston University
Journal of Cellular Biochemistry | Year: 2012

Heat shock protein (HSP) levels are elevated in breast cancer and are molecular targets for novel therapies. HSPs were first observed as proteins induced in massive amounts in normal cells exposed to stresses that lead to protein denaturation. Their expanded expression in mammary carcinoma appears to be largely due to the proliferation of malfolded mutant proteins and overexpressed oncoproteins that trigger transcription of HSP genes. HSPs play major roles in malignant transformation and progression mediated through their intrinsic molecular chaperone properties. These permit the emergence of new malignant traits through the facilitated accumulation of altered oncoproteins. The elevation of HSP concentrations in mammary carcinoma is at least partially dependent on heat shock transcription factor 1 (HSF1), a protein that responds to unfolded proteins and leads to HSP transcription. HSF1 activation has additional downstream activities, crucial for emergence of the breast cancer phenotype and these include activated cell signaling, HSP-mediated ability to evade apoptosis and senescence and an HSF1-dependent bias in transcriptional activity towards a metastatic phenotype. The HSPs are currently being targeted in breast cancer therapy and effective drugs for Hsp90 have been synthesized and evaluated in clinical trial. Mammary carcinoma cells also contain abundant quantities of HSP-tumor antigen complexes and these complexes are being used to develop effective tumor vaccine approaches that provide personalized therapy for each individual's cancer. © 2011 Wiley Periodicals, Inc.


Ochoa H.,CSIC - Institute of Materials Science | Castro Neto A.H.,National University of Singapore | Castro Neto A.H.,Boston University | Guinea F.,CSIC - Institute of Materials Science
Physical Review Letters | Year: 2012

The differences between spin relaxation in graphene and in other materials are discussed. For relaxation by scattering processes, the Elliot-Yafet mechanism, the relation between the spin and the momentum scattering times, acquires a dependence on the carrier density, which is independent of the scattering mechanism and the relation between mobility and carrier concentration. This dependence puts severe restrictions on the origin of the spin relaxation in graphene. The density dependence of the spin relaxation allows us to distinguish between ordinary impurities and defects which modify locally the spin-orbit interaction. © 2012 American Physical Society.


Oldham M.A.,Boston University
Addiction science & clinical practice | Year: 2012

Alcohol withdrawal delirium (AWD) is associated with significant morbidity and mortality. Pellagra (niacin deficiency) can be a cause of delirium during alcohol withdrawal that may often be overlooked. We present a three-patient case series of pellagrous encephalopathy (delirium due to pellagra) presenting as AWD. We provide a brief review of pellagra's history, data on pellagra's epidemiology, and discuss pellagra's various manifestations, particularly as related to alcohol withdrawal. We conclude by providing a review of existing guidelines on the management of alcohol withdrawal, highlighting that they do not include pellagrous encephalopathy in the differential diagnosis for AWD. Though pellagra has been historically described as the triad of dementia, dermatitis, and diarrhea, it seldom presents with all three findings. The neurocognitive disturbance associated with pellagra is better characterized by delirium rather than dementia, and pellagra may present as an isolated delirium without any other aspects of the triad. Although endemic pellagra is virtually eradicated in Western countries, it continues to present as pellagrous encephalopathy in patients with risk factors for malnutrition such as chronic alcohol intake, homelessness, or AIDS. It may often be mistaken for AWD. Whenever pellagra is suspected, treatment with oral nicotinamide (100 mg three times daily for 3-4 weeks) prior to laboratory confirmation is recommended as an inexpensive, safe, and potentially life-saving intervention.


Chamon C.,Boston University | Mucciolo E.R.,University of Central Florida
Physical Review Letters | Year: 2012

We propose a form of parallel computing on classical computers that is based on matrix product states. The virtual parallelization is accomplished by representing bits with matrices and by evolving these matrices from an initial product state that encodes multiple inputs. Matrix evolution follows from the sequential application of gates, as in a logical circuit. The action by classical probabilistic one-bit and deterministic two-bit gates such as NAND are implemented in terms of matrix operations and, as opposed to quantum computing, it is possible to copy bits. We present a way to explore this method of computation to solve search problems and count the number of solutions. We argue that if the classical computational cost of testing solutions (witnesses) requires less than O(n2) local two-bit gates acting on n bits, the search problem can be fully solved in subexponential time. Therefore, for this restricted type of search problem, the virtual parallelization scheme is faster than Grover's quantum algorithm. © 2012 American Physical Society.


Zaia J.,Boston University
Molecular and Cellular Proteomics | Year: 2013

The fact that sulfated glycosaminoglycans (GAGs) are necessary for the functioning of all animal physiological systems drives the need to understand their biology. This understanding is limited, however, by the heterogeneous nature of GAG chains and their dynamic spatial and temporal expression patterns. GAGs have a regulated structure overlaid by heterogeneity but lack the detail necessary to build structure/function relationships. In order to provide this information, we need glycomics platforms that are sensitive, robust, high throughput, and information rich. This review summarizes progress on mass-spectrometry-based GAG glycomics methods. The areas covered include disaccharide analysis, oligosaccharide profiling, and tandem mass spectrometric sequencing. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


Once thought to be a chromosomal aberration associated with absolute sterility, Klinefelter syndrome may now be potentially treatable by testicular sperm retrieval coupled with intracytoplasmic sperm injection. With these therapeutic advances, azoospermic 47,XXY men now may have an opportunity for biological paternity. However, our knowledge of the basic mechanisms underlying germ cell loss and Leydig cell compromise is lagging, and is just now beginning to evolve and provide answers to some of the field's most vexing questions: how to maximize and preserve fertility in Klinefelter males many years or even decades before they wish to actively pursue fatherhood. This article reviews the development of the androgenic and spermatogenic compartments of the Klinefelter testis through puberty, and recommends that it is only with a clear understanding of the basic facts that a rational, considered approach to fertility optimization and preservation can be determined. Copyright © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.


Pearce E.N.,Boston University
Journal of Trace Elements in Medicine and Biology | Year: 2012

Dietary iodine requirements are increased in pregnancy due to increased thyroid hormone production, increased renal iodine losses, and fetal iodine requirements. Adverse effects of iodine deficiency in pregnancy include maternal and fetal goiter, cretinism, intellectual impairments, neonatal hypothyroidism, and increased pregnancy loss and infant. Dietary iodine requirements remain increased in lactation due to the concentration of iodine in breast milk. Iodine deficiency remains a significant global public health problem. Excess iodine ingestion in pregnancy, while a relatively uncommon problem, may also have adverse fetal effects. However, the safe upper limit for chronic iodine ingestion in pregnancy and lactation is not currently well defined. © 2012 Elsevier GmbH.


Katira P.,University of Texas at Austin | Zaman M.H.,Boston University | Bonnecaze R.T.,University of Texas at Austin
Physical Review Letters | Year: 2012

Tumor growth and metastasis are ultimately mechanical processes involving cell migration and uncontrolled division. Using a 3D discrete model of cells, we show that increased compliance as observed for cancer cells causes them to grow at a much faster rate compared to surrounding healthy cells. We also show how changes in intercellular binding influence tumor malignancy and metastatic potential. These findings suggest that changes in the mechanical properties of cancer cells is the proximate cause of uncontrolled division and migration and various biochemical factors drive cancer progression via this mechanism. © 2012 American Physical Society.


Evans G.W.,Cornell University | Fuller-Rowell T.E.,University of Wisconsin - Madison | Doan S.N.,Boston University
Pediatrics | Year: 2012

OBJECTIVES: We tested whether early childhood risk exposures are related to weight gain in adolescence and evaluate an underlying mechanism, self-regulatory behavior, for the risk-obesity link. METHODS: Cumulative risk exposure to 9 sociodemographic (eg, poverty), physical (eg, substandard housing), and psychosocial (eg, family turmoil) stressors was assessed in 244 nine-year-old children. BMI was calculated at age 9 and then 4 years later. At age 9, children's ability to delay gratification as an index of self-regulatory behavior was assessed. Path analyses were then estimated to evaluate our mediational model (Cumulative risk → Self-regulation → BMI) over a 4-year period in a prospective, longitudinal design. RESULTS: Nine-year-old children exposed to a greater accumulation of multiple risk factors show larger gains in adiposity over the next four year period, net of their initial BMI. These gains in BMI during early adolescence are largely accounted for by deteriorated self-regulatory abilities among children facing more cumulative risks. CONCLUSIONS: Early childhood risk exposure leads to larger gains in BMI in adolescence. Given the importance of childhood adiposity to the development of obesity later in life, understanding the underlying mechanisms that link early experience to weight gain is an essential task. Deficiencies in self-regulation in response to chronic stress appears to be an important agent in the obesity epidemic. Copyright © 2012 by the American Academy of Pediatrics.


Wilson K.C.,Boston University
European Respiratory Review | Year: 2015

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes. © ERS 2015.


Merkin V.G.,Boston University | Lyon J.G.,Dartmouth College
Journal of Geophysical Research: Space Physics | Year: 2010

In common treatment of magnetosphere-ionosphere coupling at high latitudes, the ionosphere is represented by a thin conducting spherical shell, which closes field-aligned currents generated in the magnetosphere. In this approach, the current continuity yields a Poisson equation for the electrostatic potential associated with the ionospheric convection pattern. Solution of the Poisson equation then provides a means of self-consistently describing magnetospheric and ionospheric plasma convection with a feedback of one on the other. While the high-latitude ionospheric convection is driven by the solar wind and magnetosphere interaction, at lower latitudes atmospheric neutral winds start to dominate. The question that arises then is whether and how midlaltitude and low-latitude ionospheric convection affects high-latitude ionospheric and magnetospheric convection. In global magnetospheric models, ionospheric convection equatorward of the low-latitude boundary is excluded from the simulation domain. However, the boundary condition applied at that boundary to the electrostatic potential may be used as a proxy of this convection. In this paper, we explore effects that different idealized low-latitude boundary conditions have on the magnetospheric configuration simulated by the Lyon-Fedder-Mobarry global magnetohydrodynamic model. To this end, we perform a number of idealized simulations different only in the low-latitude ionospheric boundary condition used. We find that the behavior of the system can be influenced rather significantly by the different boundary conditions, which is expressed by changes in the evolution of the polar cap potential, global magnetospheric convection, and plasma pressure distribution in the magnetotail and on the dayside. The differences in the cross-polar cap potential can reach up to >10%, dependent on the boundary condition used. In the magnetosphere the low-latitude ionospheric boundary condition affects the strength and location of the plasma outflow from the distant tail x-line and the subsequent earthward convection. Changes in the plasma pressure distribution on the nightside are accompanied by noticeable differences in the shape of the magnetotail. We confirm that the changes in the magnetospheric and ionospheric configuration are not just temporal deviations of the system from the same average dynamical state by considering 1 h averages of the magnetospheric flow and pressure distribution. These results verify that the simulated system reaches similar but distinctly different dynamical states dependent on the low-latitude boundary condition applied. Copyright 2010 by the American Geophysical Union.


Rubio-Tapia A.,Mayo Medical School | Hill I.D.,Wake forest University | Kelly C.P.,Beth Israel Deaconess Medical Center | Calderwood A.H.,Boston University | Murray J.A.,Mayo Medical School
American Journal of Gastroenterology | Year: 2013

This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients. © 2013 by the american College of Gastroenterology.


Gilmore T.D.,Boston University
Current topics in microbiology and immunology | Year: 2011

As described extensively in this issue, NF-κB transcription factors regulate a number of important physiological processes, including inflammation and immune responses, cell growth and survival, and the expression of certain viral genes. Moreover, NF-κB activity is elevated in and contributes to the pathology of several human diseases, including many cancers and chronic inflammatory diseases. Therefore, there has been great interest in the characterization and development of methods to limit NF-κB signaling for pharmacological intervention. This article describes some of the approaches that have been employed to inhibit NF-κB using in vitro and in vivo experimental models. Moreover, some examples of the clinical use of NF-κB inhibitors are discussed, primarily for the treatment of two B-cell malignancies, multiple myeloma and diffuse large B-cell lymphoma. Finally, the rationale and strategies for inhibiting specific NF-κB subunit activity for disease therapy are discussed.


Runger T.M.,Boston University
Journal of Investigative Dermatology | Year: 2013

Data on the wavelength dependence of UV-induced formation of DNA damage and skin cancer have been available for quite some time, but a detailed in vivo action spectrum of mutation formation has not yet been reported so far. This important information gap is filled by Ikehata et al. in this issue. Their findings question several aspects of our current thinking about UV-induced mutagenesis and carcinogenesis. © 2013 The Society for Investigative Dermatology.


Clemens D.P.,Boston University
Astrophysical Journal | Year: 2012

The L183 (= L134N) dark molecular cloud has been probed using deep near-infrared imaging polarimetry of stars to beyond 14mag in H band (1.6μm), using the Mimir instrument on the 1.83m Perkins Telescope. Nearly 400arcmin2 were surveyed, including the dense core in L183, as seen in WISE Band 3 (12μm) extinction, and the near surroundings, revealing 35 stars with either detected polarizations or significant upper limits. Stars with detected polarizations are reddened if closer than 8arcmin (0.25pc at the 110pc cloud distance) and unreddened beyond. The polarimetric sample probes as close to the core as 3arcmin (0.1pc), where AV 14mag. Compared to the relatively unextincted surrounding stars, the reddened stars show no increase in polarization with extinction, suggesting that all of the polarization is induced in the outer layers of the cloud. This 0.25pc radius envelope magnetic field does show a strong interaction with the L183 dark cloud. The envelope field is also virtually perpendicular, on the plane of the sky, to the field seen at 850μm, though more closely aligned with the rotation axis of the dense gas core. The physical size scale at which the envelope and the core magnetic fields either decouple from each other or strongly modify their directions must be inside the 0.1pc region probed here. © 2012 The American Astronomical Society. All rights reserved.


In global environmental cooperation, legally binding agreements remain a customary way for states to set common goals and standards. This article analyzes the Minamata Convention on Mercury by addressing three questions: First, how did linkages to earlier agreements shape the negotiations? Second, what were the main legal and political issues during the negotiations? Third, what are the major issues moving forward with treaty implementation and mercury abatement? The analysis shows that the decision to start treaty negotiations was influenced by related policy developments on hazardous chemicals as well as differences in national interests. Five sets of issues dominated the negotiations: 1) supply and trade, 2) products and processes, 3) emissions and releases, 4) artisanal and small-scale gold mining, and 5) resources and compliance. The article concludes that future mercury abatement hinges on the parties' ability to move beyond the initial mandates, as the convention may affect decisions by a wide range of public, private, and civil society actors. © 2014 by the Massachusetts Institute of Technology.


Spiegel J.H.,Boston University
Laryngoscope | Year: 2011

Objective/Hypothesis: Information determined by viewing a face includes familiarity, emotion, attractiveness, and gender. However, the specific facial characteristics that enable one to identify gender are largely unknown. Research suggests that femininity is a critical component of beauty; however, the most important identifiers of a womans face are unknown. The objectives of this article were: 1) determine the area of the face most significant in identifying female gender, 2) determine if individuals with gender-confirming surgery of the face are identified as male or female, 3) review the efficacy and safety of a series of feminizing forehead cranioplasties. Study Design: 1) Prospective evaluation of computer simulated changes and postoperative patient images, 2) retrospective review of medical records. Methods: 1) Photographs of men were digitally altered to adjust (a) the forehead (b) the nose/lip, (c) the jaw. Each change a, b, or c is done in isolation in both frontal and profile views. Subjects were shown the three profile and the three frontal photographs and asked to rate which of each set is the most feminine. 2) Photographs of male-to-female (MTF) transgender patients who may have had forehead, midface, or jaw surgery were shown to subjects. Subjects were asked the gender of the person in each picture. 3) Medical records and operative reports of 168 patients who underwent feminizing forehead cranioplasty were evaluated for surgical technique, and complications. Results: For Experiment 1, in frontal views of all subjects the forehead modification was selected as the most feminine, whereas in no cases was the forehead modification selected as least feminine by a majority of respondents. For the profile view, again the forehead modification was selected as most feminine by respondents for the majority of subjects, but surprisingly, the strength of the association between frontal modification and femininity, while strongly statistically significant, was more evident in the frontal view. For Experiment 2, among transgendered faces shown to viewers, 82% of postoperative forehead modifications were judged as women, 87% of postoperative midface modifications were judged as women, and 85% of postoperative lower faces were judged as women. For section 3, the review of safety and technique in 168 feminizing forehead cranioplasties, there were three basic surgical techniques utilized with only three complications for an overall complication rate of 1.8%. Conclusions: Feminization of the forehead through cranioplasty is safe and has a significant impact in determining the gender of the patient. The strong association between femininity and attractiveness can now be more specifically attributed to the upper third of the face and the interplay of the glabellar prominence of the forehead, along with the eyebrow shape and position, and hairline shape and position. These results have strong implications for a paradigm shift in the method of facial analysis used to select aesthetic procedures and illuminates the processes by which femininity and attractiveness are interpreted in faces. © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.


Baxter E.F.,Boston University | Caddick M.J.,Virginia Polytechnic Institute and State University
Geology | Year: 2013

The release of volatiles from subducting lithologies is a crucial triggering process for arc magmatism, seismicity, the growth and maturation of continents, and the global geological water-CO2 cycle. While models exist to predict slab volatile release from hydrous phases, it is challenging to reconstruct and test these fluid fluxes in nature. Here we show that the growth of garnet may be used as a proxy for devolatilization at blueschist to lower eclogite facies conditions in subduction zones. Using thermodynamic analysis including the effects of garnet fractionation and fluid removal, we show the proportional relationship between garnet and water production in two end-member crustal lithologies (pelitic sediment and hydrated mid-oceanic-ridge basalt [MORB]) in three representative subduction geotherms. Dehydrating minerals such as lawsonite, chlorite, amphibole, and epidote contribute to garnet growth, especially between ~1.4 and 3.0 GPa where geophysical models and observations predict dehydration. The average production ratio for altered MORB compositions is 0.52 (wt% water as fluid per vol% garnet) in cooler geotherms (Honshu [Japan] and Nicaragua) and 0.27 in hotter geotherms (Cascadia [North America]), whereas for pelite the production ratios are about half (0.24 and 0.13, respectively). Garnet growth correlates with production of 3.3-5.9 wt% water in hydrated MORB and 1.8-3.1 wt% water in pelite, representing 42%-100% of the water lost between 0.5 and 6.5 GPa from a fully saturated starting material. Garnet abundance, its pressure-temperature growth span, and its growth chronology may be used to recognize, reconstruct, and test models for progressive subduction zone dehydration. © 2013 Geological Society of America.


Wolozin B.,Boston University
Molecular Neurodegeneration | Year: 2012

The protein aggregation that occurs in neurodegenerative diseases is classically thought to occur as an undesirable, nonfunctional byproduct of protein misfolding. This model contrasts with the biology of RNA binding proteins, many of which are linked to neurodegenerative diseases. RNA binding proteins use protein aggregation as part of a normal regulated, physiological mechanism controlling protein synthesis. The process of regulated protein aggregation is most evident in formation of stress granules. Stress granules assemble when RNA binding proteins aggregate through their glycine rich domains. Stress granules function to sequester, silence and/or degrade RNA transcripts as part of a mechanism that adapts patterns of local RNA translation to facilitate the stress response. Aggregation of RNA binding proteins is reversible and is tightly regulated through pathways, such as phosphorylation of elongation initiation factor 2. Microtubule associated protein tau also appears to regulate stress granule formation. Conversely, stress granule formation stimulates pathological changes associated with tau. In this review, I propose that the aggregation of many pathological, intracellular proteins, including TDP-43, FUS or tau, proceeds through the stress granule pathway. Mutations in genes coding for stress granule associated proteins or prolonged physiological stress, lead to enhanced stress granule formation, which accelerates the pathophysiology of protein aggregation in neurodegenerative diseases. Over-active stress granule formation could act to sequester functional RNA binding proteins and/or interfere with mRNA transport and translation, each of which might potentiate neurodegeneration. The reversibility of the stress granule pathway also offers novel opportunities to stimulate endogenous biochemical pathways to disaggregate these pathological stress granules, and perhaps delay the progression of disease. © 2012 Wolozin; licensee BioMed Central Ltd.


Declercq E.,Boston University
Journal of Midwifery and Women's Health | Year: 2012

Introduction: Data on attendance at birth by midwives in the United States have been available on the national level since 1989. Rates of certified nurse-midwife (CNM)-attended births more than doubled between 1989 (3.3% of all births) and 2002 (7.7%) and have remained steady since. This article examines trends in midwife-attended births from 1989 to 2009. Methods: The data in this report are based on records gathered as part of the US National Standard Certificate of Live Birth from a public use Web site, Vital Stats, that allows users to create and download specialized tables. Results: Between 2007 and 2009, the proportion of all births attended by CNMs increased by 4% from 7.3% of all births to 7.6% and a total of 313,516. This represents a decline in total births attended by CNMs from 2008 but a higher proportion of all births because total US births dropped at a faster rate. The proportion of vaginal births attended by CNMs reached an all-time high of 11.4% in 2009. There were strong regional patterns to the distribution of CNM-attended births. Births attended by "other midwives" rose to 21,787 or 0.5% of all US births, and the total proportion of all births attended by midwives reached an all-time high of 8.1%. The race/ethnicity of mothers attended by CNMs has shifted over the years. In 1990, CNMs attended a disproportionately high number of births to non-white mothers, whereas in 2009, the profile of CNM births mirrors the national distribution in race/ethnicity. Discussion: Midwife-attended births in the United States are increasing. The geographic patterns in the distribution of midwife-attended births warrant further study. © 2012 by the American College of Nurse-Midwives.


Apovian C.M.,Boston University | Aronne L.J.,New York Medical College
JAMA - Journal of the American Medical Association | Year: 2013

BACKGROUND: Obese individuals who have failed to achieve adequate weight loss with lifestyle changes have limited nonsurgical therapeutic options. We evaluated the efficacy and tolerability of zonisamide, an antiepileptic drug, for enhancing weight loss in obese patients receiving diet and lifestyle guidance. METHODS: This was a 1-year, randomized, double-blind, placebo-controlled trial conducted from January 9, 2006, through September 20, 2011, at Duke University Medical Center. A total of 225 obese (mean [SD] body mass index, 37.6 [4.9]) participants included 134 women (59.6%) and 91 men (40.4%) without diabetes mellitus. (Body mass index is calculated as weight in kilograms divided by height in meters squared.) Interventions were daily dosing with placebo (n = 74), 200mg of zonisamide (n = 76), or 400 mg of zonisamide (n = 75), in addition to diet and lifestyle counseling by a dietitian for 1 year. Primary outcome was change in body weight at 1 year. RESULTS: Of the 225 randomized patients, 218 (96.9%) provided 1-year follow-up assessments. Change in body weight was -4.0 kg (95% CI, -5.8 to -2.3 kg; least squares mean, -3.7%) for placebo, -4.4 kg (-6.1 to -2.6 kg; -3.9%; P = .79 vs placebo) for 200 mg of zonisamide, and -7.3 kg (-9.0 to -5.6 kg; -6.8%; P = .009 vs placebo) for 400 mg of zonisamide. In the categorical analysis, 23 (31.1%) assigned to placebo, 26 (34.2%; P = .72) assigned to 200mg of zonisamide, and 41 (54.7%; P = .007) assigned to 400 mg of zonisamide achieved 5% or greater weight loss; for 10% or greater weight loss, the corresponding numbers were 6 (8.1%), 17 (22.4%; P = .02), and 24 (32.0%; P < .001). Gastrointestinal, nervous system, and psychiatric adverse events occurred at a higher incidence with zonisamide than with placebo. CONCLUSION: Zonisamide at the daily dose of 400 mg moderately enhanced weight loss achieved with diet and lifestyle counseling but had a high incidence of adverse events.


Krieger N.,Boston University | Krieger N.,Harvard University
American Journal of Public Health | Year: 2013

How we think about biology-in historical, ecological, and societal context-matters for framing causes of and solutions to health inequities. Drawing on new insights from ecological evolutionary developmental biology and ecosocial theory, I question dominant gene-centric and ultimately static approaches to conceptualizing biology, using the example of the breast cancer estrogen receptor (ER). Analyzed in terms of its 4 histories-societal, individual (life course), tumor (cellular pathology), and evolutionary-the ER is revealed as a flexible characteristic of cells, tumors, individuals, and populations, with magnitudes of health inequities tellingly changing over time. This example suggests our science will likely be better served by conceptualizing disease and its biomarkers, along with changing magnitudes of health inequities, as embodied history-that is, emergent embodied phenotype, not innate biology. Copyright © 2012 by the American Public Health Association®.


Doerrer L.H.,Boston University
Dalton Transactions | Year: 2010

This Perspective highlights our efforts to assemble infinite chains of metal atoms in double salts of the form [M]+[M]- under the complementary influences of metallophilic interactions and electrostatic attraction. Our design strategy necessarily incorporates the significant steric constraints of one-dimensional assemblies as well as the more subtle and challenging electronic tuning of weak dispersion forces. © 2010 The Royal Society of Chemistry.


Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition,since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. © 2011 by the authors; licensee MDPI, Basel, Switzerland.


Gursky O.,Boston University
FEBS Letters | Year: 2014

ApoA-II is the second-major protein of high-density lipoproteins. C-terminal extension in human apoA-II or point substitutions in murine apoA-II cause amyloidosis. The molecular mechanism of apolipoprotein misfolding, from the native predominantly α-helical conformation to cross-β-sheet in amyloid, is unknown. We used 12 sequence-based prediction algorithms to identify two ten-residue segments in apoA-II that probably initiate β-aggregation. Previous studies of apoA-II fragments experimentally verify this prediction. Together, experimental and bioinformatics studies explain why the C-terminal extension in human apoA-II causes amyloidosis and why, unlike murine apoA-II, human apoA-II normally does not cause amyloidosis despite its unusually high sequence propensity for β-aggregation. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Novogrodsky R.,Boston University
Clinical Linguistics and Phonetics | Year: 2013

In the current study, storytelling and story retelling by children with autism spectrum disorder (ASD) were analyzed to explore ambiguous third-person pronoun use in narratives. Twenty-three children diagnosed with ASD aged 6;1 to 14;3 and 17 typically-developing (TD) children aged 5;11 to 14;4 participated in the study. In the retelling task, no significant difference between the groups was found, suggesting that in less challenging tasks, children with ASD produce third-person subject pronouns appropriately. In the storytelling task, children with ASD produced more ambiguous third-person subject pronouns than did the TD children. The findings suggest a model in which children with ASD show deficits in the pragmatic domain of producing narratives. © 2013 Informa UK Ltd.


Bewley K.D.,Boston University
Biochemical Society transactions | Year: 2012

Shewanella oneidensis MR-1 has the ability to use many external terminal electron acceptors during anaerobic respiration, such as DMSO. The pathway that facilitates this electron transfer includes the decahaem cytochrome DmsE, a paralogue of the MtrA family of decahaem cytochromes. Although both DmsE and MtrA are decahaem cytochromes implicated in the long-range electron transfer across a ~300 Å (1 Å=0.1 nm) wide periplasmic 'gap', MtrA has been shown to be only 105 Å in maximal length. In the present paper, DmsE is further characterized via protein film voltammetry, revealing that the electrochemistry of the DmsE haem cofactors display macroscopic potentials lower than those of MtrA by 100 mV. It is possible this tuning of the redox potential of DmsE is required to shuttle electrons to the outer-membrane proteins specific to DMSO reduction. Other decahaem cytochromes found in S. oneidensis, such as the outer-membrane proteins MtrC, MtrF and OmcA, have been shown to have electrochemical properties similar to those of MtrA, yet possess a different evolutionary relationship.


We study the effect of dye-dye interactions in labeled double-stranded DNA molecules on the Förster resonance energy transfer (FRET) efficiency at the single-molecule level. An extensive analysis of internally labeled double-stranded DNA molecules in bulk and at the single-molecule level reveals that donor-acceptor absolute distances can be reliably extracted down to approximately 3-nm separation, provided that dye-dye quenching is accounted for. At these short separations, we find significant long-lived fluorescence fluctuations among discrete levels originating from the simultaneous and synchronous quenching of both dyes. By comparing four different donor-acceptor dye pairs (TMR-ATTO647N, Cy3-ATTO647N, TMR-Cy5, and Cy3-Cy5), we find that this phenomenon depends on the nature of the dye pair used, with the cyanine pair Cy3-Cy5 showing the least amount of fluctuations. The significance of these results is twofold: First, they illustrate that when dye-dye quenching is accounted for, single-molecule FRET can be used to accurately measure inter-dye distances, even at short separations. Second, these results are useful when deciding which dye pairs to use for nucleic acids analyses using FRET. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.


Declercq E.,Boston University
Journal of Midwifery and Women's Health | Year: 2015

Introduction: Data on attendance at birth by midwives in the United States have been available on the national level since 1989, allowing for the documentation of long-term trends. New items on payer source and prepregnancy body mass index (BMI) from a 2003 revision of the birth certificate provide an opportunity to examine additional aspects of US midwifery practice. Methods: The data in this report are based on records on birth attendant gathered as part of the US National Standard Certificate of Live Birth from a public use Web site, Vital Stats (http://www.cdc.gov/nchs/VitalStats.htm), which allows users to create and download specialized tables. Analysis of new items on prepregnancy BMI and birth payer source are limited to the 38 states (86% of US births) that adopted the revised birth certificate by 2012. Results: Between 1989 and 2012, the proportion of all births attended by certified nurse-midwives (CNMs) increased from 3.3% to 7.9%. The proportion of vaginal births attended by CNMs reached an all-time high of 11.9%. Births attended by "other midwives" (typically certified professional midwives) rose to a peak of 28,343, or 0.7% of all US births. The distribution of payer source for CNM-attended births (44% Medicaid; 44% private insurance; 6% self-pay) is very similar to the national distribution, whereas the majority (53%) of births attended by other midwives are self-pay. Women whose births are attended by other midwives are less likely (13%) to have a prepregnancy BMI in the obese range than women attended by CNMs (19%) or overall (24%). Discussion: The total number of births attended by CNMs and other midwives has remained steady or grown at a time when total US births have declined, resulting in the largest proportions of midwife-attended births in the quarter century that such data have been collected. © 2015 by the American College of Nurse-Midwives.


Eichenbaum H.,Boston University
Neuron | Year: 2015

The traditional view of the hippocampus is that it creates a cognitive map to navigate physical space. Here, in this issue of Neuron, Tavares et al. (2015) show that the human hippocampus maps dimensions of social space, indicating a function in the service of navigating everyday life. © 2015 Elsevier Inc.


Nikolajczyk B.S.,Boston University
Cytokine | Year: 2010

B lymphocytes play roles in many auto-immune diseases characterized by unresolved inflammation, and B cell ablation is proving to be a relatively safe, effective treatment for such diseases. B cells function, in part, as important sources of regulatory cytokines in auto-immune disease, but B cell cytokines also play roles in other non-auto-immune inflammatory diseases. B cell ablation may therefore benefit inflammatory disease patients in addition to its demonstrated efficacy in auto-immune disease. Current ablation drugs clear both pro- and anti-inflammatory B cell subsets, which may unexpectedly exacerbate some pathologies. This possibility argues that a more thorough understanding of B cell function in human inflammatory disease is required to safely harness the clinical promise of B cell ablation. Type 2 diabetes (T2D) and periodontal disease (PD) are two inflammatory diseases characterized by little autoimmunity. These diseases are linked by coincident presentation and alterations in toll-like receptor (TLR)-dependent B cell cytokine production, which may identify B cell ablation as a new therapy for co-affected individuals. Further analysis of the role B cells and B cell cytokines play in T2D, PD and other inflammatory diseases is required to justify testing B cell depletion therapies on a broader range of patients. © 2010 Elsevier Ltd.


Hiller G.,TU Dortmund | Schmaltz M.,Boston University
Journal of High Energy Physics | Year: 2015

Abstract: Ratios of branching fractions of semileptonic B decays, (B → Hμμ) over (B → Hee) with H = K, K∗, Xs, K0(1430), ϕ, . . are sensitive probes of lepton universality. In the Standard Model, the underlying flavor changing neutral current process b → sℓℓ is lepton flavor universal. However models with new flavor violating physics above the weak scale can give substantial non-universal contributions. The leading contributions from such new physics can be parametrized by effective dimension six operators involving left- or right-handed quarks. We show that in the double ratios (Formula presented) the dependence on new physics coupling to left-handed quarks cancels out. Thus a measurement of any of these double ratios is a clean probe of flavor nonuniversal physics coupling to right-handed quarks. We also point out that the observables (Formula presented.) and Rϕ depend on the same combination of Wilson coefficients and therefore satisfy simple consistency relations. © 2015, The Author(s).


Baicker K.,Boston University | Cutler D.,Harvard University | Song Z.,Harvard University
Health Affairs | Year: 2010

Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes. © 2010 Project HOPE-The People-to-People Health Foundation, Inc.


Spira A.,Boston University
Cancer Prevention Research | Year: 2010

This perspective on Boyle et al. (beginning on page 266 in this issue of the journal) explores transcriptomic profiling of upper airway epithelium as a biomarker of host response to tobacco smoke exposure. Boyle et al. have shown a striking relationship between smoking-related gene expression changes in the mouth and bronchus. This relationship suggests that buccal gene expression may serve as a relatively noninvasive surrogate marker of the physiologic response of the lung to tobacco smoke that could be used in large-scale screening and chemoprevention studies for lung cancer. ©2010 AACR.


Gottlieb L.,University of California at San Francisco | Sandel M.,Boston University | Adler N.E.,University of California at San Francisco
JAMA Internal Medicine | Year: 2013

Despite strong evidence linking patients' social circumstances to their health, little guidance exists for health care practitioners and institutions on addressing social needs in clinical settings. Current approaches to social determinants generally focus on population-level and policy interventions; these overlook individual and clinical innovations within health care that can address patients' social circumstances. This article proposes a framework for how social determinants interventions in the health care system can be construed across 3 tiers - patient, institution, and broader population - and describes ways to collect data and target interventions at these levels. ©2013 American Medical Association. All rights reserved.


DeSilva J.M.,Boston University
American Journal of Physical Anthropology | Year: 2010

The midtarsal break was first described in this journal nearly 75 years ago to explain the ability of non-human primates to lift their heel independently of the rest of the foot. Since the initial description of the midtarsal break, the calcaneocuboid joint has been assumed to be the anatomical source of this motion. Recently, however, it has been suggested that the midtarsal break may occur at the cuboid-metatarsal joint, rather than at the calcaneocuboid joint. Data compiled from X-rays, dissections, manual manipulation of living primate feet, video of captive catarrhines, and osteological specimens concur that the midtarsal break is a complex motion caused by dorsiflexion at both joints with the cuboid-metatarsal joint contributing roughly 2/3 of total midfoot dorsiflexion, and the calcaneocuboid joint only about 1/3 of total midfoot dorsiflexion. The convexity of the proximal articular surface of the fourth and fifth metatarsals and corresponding concave cuboid facets provide skeletal correlates for the presence of midfoot dorsiflexion at the cuboid-metatarsal joint. Study of hominin metatarsals from Australopithecus afarensis, A. africanus, Homo erectus, and the metatarsals and a cuboid from the OH 8 foot show little capacity for dorsiflexion at the cuboid-metatarsal joint. These results suggest that hominins may have already evolved a stable midfoot region well adapted for the push-off phase of bipedalism by at least 3.2 million years ago. These data illuminate the evolution of the longitudinal arch and show further evidence of constraints on the arboreal capacity in early hominins. © 2009 Wiley-Liss, Inc.


Carey K.,Boston University
Health Economics (United Kingdom) | Year: 2015

If patients are discharged from the hospital prematurely, many may need to return within a short period of time. This paper investigates the relationship between length of stay and readmission within 30 days of discharge from an acute care hospitalization. It applies a two-part model to data on Medicare patients treated for heart attack in New York state hospitals during 2008 to obtain the expected cost of readmission associated with length of stay. The expected cost of a readmission is compared with the marginal cost of an additional day in the initial stay to examine the cost trade-off between an extra day of care and the expected cost of readmission. The cost of an additional day of stay was offset by expected cost savings from an avoided readmission in the range of 15% to 65%. Results have implications for payment reform based on bundled payment reimbursement mechanisms. Copyright © 2014 John Wiley & Sons, Ltd.


Kramer M.A.,Boston University | Cash S.S.,Massachusetts General Hospital | Cash S.S.,Harvard University
Neuroscientist | Year: 2012

The brain is naturally considered as a network of interacting elements which, when functioning properly, produces an enormous range of dynamic, adaptable behavior. However, when elements of this network fail, pathological changes ensue, including epilepsy, one of the most common brain disorders. This review examines some aspects of cortical network organization that distinguish epileptic cortex from normal brain as well as the dynamics of network activity before and during seizures, focusing primarily on focal seizures. The review is organized around four phases of the seizure: the interictal period, onset, propagation, and termination. For each phase, the authors discuss the most common rhythmic characteristics of macroscopic brain voltage activity and outline the observed functional network features. Although the characteristics of functional networks that support the epileptic seizure remain an area of active research, the prevailing trends point to a complex set of network dynamics between, before, and during seizures. © The Author(s) 2012.


Jackson M.G.,Boston University | Shirey S.B.,Carnegie Institution of Washington
Earth and Planetary Science Letters | Year: 2011

Samoan shield-stage lavas (from the islands of Ta'u, Savai'i, and Ofu and the seamounts of Vailulu'u and Malumalu) with Os concentrations >30ppt have 187Os/ 188Os ratios that exhibit a narrow range of values between 0.128 and 0.132. Lavas with ≤30ppt Os show more radiogenic 187Os/ 188Os ratios, in some cases as high as 0.191, suggesting that the 187Os/ 188Os ratios of the extreme Samoan EM2 (enriched mantle 2) lavas likely have been compromised by assimilation of altered oceanic crust. The 187Os/ 188Os ratios for rejuvenated-stage lavas from Savai'i are lower than shield lavas, and they exhibit some of the lowest 187Os/ 188Os ratios in the global ocean island basalt database (Hauri and Hart, 1993). The difference may owe to contamination of the rejuvenated lavas with unradiogenic Os from disaggregated xenoliths from the mantle lithosphere, and their low Os isotopic composition does not reflect the EM2 mantle source of magmas. The limited range in 187Os/ 188Os ratios of the higher Os-abundance shield lavas (0.128-0.132), coupled with a tremendous range of 87Sr/ 86Sr (0.7045-0.7114), are characteristics of the EM2 source that can be explained by mixing a continental crustal sediment characterized by a high Sr/Os (~10 7) with a mantle peridotite that has low Sr/Os (~10 4).Os abundances for nine whole rocks and their olivine phenocrysts show opposite trends with respect to whole rock MgO content: olivines have less than 0.1ppb Os at 15wt.% MgO and increase to 1-2ppb Os in lavas with 8wt.% MgO. Even though the Os isotopic composition of an evolved lava is susceptible to crustal assimilation, olivine phenocrysts with high Os concentrations preserve the pre-assimilation magmatic 187Os/ 188Os ratio. For example, the range of 187Os/ 188Os ratios measured on magmatic olivines from Samoan shield lavas (0.127 to 0.130) is lower (and narrower than) the range estimated using Os-rich (>30ppt) whole rock lavas (0.128-0.132). © 2011 Elsevier B.V.


Mullen S.P.,Boston University | Shaw K.L.,Cornell University
Annual Review of Entomology | Year: 2014

The study of speciation is concerned with understanding the connection between causes of divergent evolution and the origin and maintenance of barriers to gene exchange between incipient species. Although the field has historically focused either on examples of recent divergence and its causes or on the genetic basis of reproductive isolation between already divergent species, current efforts seek to unify these two approaches. Here we integrate these perspectives through a discussion of recent progress in several insect speciation model systems. We focus on the evolution of speciation phenotypes in each system (i.e., those phenotypes causally involved in reducing gene flow between incipient species), drawing an explicit connection between cause and effect (process and pattern). We emphasize emerging insights into the genomic architecture of speciation as well as timely areas for future research. © Copyright ©2014 by Annual Reviews. All rights reserved.


Basov D.N.,University of California at San Diego | Averitt R.D.,Boston University | Van Der Marel D.,University of Geneva | Dressel M.,University of Stuttgart | Haule K.,Rutgers University
Reviews of Modern Physics | Year: 2011

Studies of the electromagnetic response of various classes of correlated electron materials including transition-metal oxides, organic and molecular conductors, intermetallic compounds with d and f electrons, as well as magnetic semiconductors are reviewed. Optical inquiry into correlations in all these diverse systems is enabled by experimental access to the fundamental characteristics of an ensemble of electrons including their self-energy and kinetic energy. Steady-state spectroscopy carried out over a broad range of frequencies from microwaves to UV light and fast optics time-resolved techniques provides complimentary prospectives on correlations. Because the theoretical understanding of strong correlations is still evolving, the review is focused on the analysis of the universal trends that are emerging out of a large body of experimental data augmented where possible with insights from numerical studies. © 2011 American Physical Society.


Guadagnoli D.,University of Savoy | Lane K.,Boston University | Lane K.,CERN
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

We present a model for calculating charged-lepton mixing matrices. These matrices are an essential ingredient for predicting lepton flavor-violating rates in the lepton number nonuniversal models recently proposed to explain anomalies in B-meson decays. The model is based on work on "constrained flavor breaking" by Appelquist, Bai and Piai relating the charged-lepton mass matrix, Mℓ, to those for the up- and down-type quarks, Mu,d. We use our recent model of lepton nonuniversality to illustrate the magnitudes of flavor-violating B-decay rates that might be expected. Decays with μτ final states generally have the highest rates by far. © 2015 The Authors.


Han X.,Boston University
ACS Chemical Neuroscience | Year: 2012

Optogenetics combines optical and genetic methods to rapidly and reversibly control neural activities or other cellular functions. Using genetic methods, specific cells or anatomical pathways can be sensitized to light through exogenous expression of microbial light activated opsin proteins. Using optical methods, opsin expressing cells can be rapidly and reversibly controlled by pulses of light of specific wavelength. With the high spatial temporal precision, optogenetic tools have enabled new ways to probe the causal role of specific cells in neural computation and behavior. Here, we overview the current state of the technology, and provide a brief introduction to the practical considerations in applying optogenetics in vivo to analyze neural circuit functions. © 2012 American Chemical Society.


Dodwell E.R.,Boston University
Calcified tissue international | Year: 2010

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain control. However, concerns regarding the potential deleterious effects of NSAIDs on bone healing have compelled many physicians to avoid NSAIDs in patients with healing fractures, osteotomies, and fusions. We systematically reviewed and analyzed the best clinical evidence regarding the effects of NSAID exposure on bone healing. Medline, Embase, and Cochrane electronic databases were searched for prospective and retrospective clinical studies of fracture, osteotomy, and fusion studies of patients with NSAID exposure and nonunion as an outcome. Study quality was assessed using the Newcastle-Ottawa Scale. Data on study design, patient characteristics, and risk estimates were extracted. Pooled effect estimates were calculated. Subanalyses were performed by bone type and by NSAID dose, duration, and route of administration. In the initial analysis of 11 cohort and case-control studies, the pooled odds ratio for nonunion with NSAID exposure was 3.0 (95% confidence interval 1.6-5.6). A significant association between lower-quality studies and higher reported odds ratios for nonunion was observed. When only higher-quality studies were considered, seven spine fusion studies were analyzed, and no statistically significant association between NSAID exposure and nonunion was identified (odds ratio = 2.2, 95% confidence interval 0.8-6.3). There was no increased risk of nonunion with NSAID exposure when only the highest-quality studies were assessed. Randomized controlled trials assessing NSAID exposure in fracture, fusion, and osteotomy populations are warranted to confirm or refute the findings of this meta-analysis of observational studies.


Spike timing dependent plasticity (STDP) has been demonstrated in various neural systems of many animals. It has been shown that STDP depends on the target and the location of the synapse and is dynamically regulated by the activity of adjacent synapses, the presence of postsynaptic calcium, presynaptic GABA inhibition or the action of neuromodulators. Recent experimental evidence has reported that the profile of STDP in the CA1 pyramidal neuron can be classified into two types depending on its dendritic location: (1) A symmetric STDP profile in the proximal to the soma dendrites, and (2) an asymmetric one in the distal dendrites. Bicuculline application revealed that GABAA is responsible for the symmetry of the STDP curve. We investigate via computer simulations how GABAA shapes the STDP profile in the CA1 pyramidal neuron dendrites when it is driven by excitatory spike pairs (doublets). The model constructed uses calcium as the postsynaptic signaling agent for STDP and is shown to be consistent with classical long-term potentiation (LTP) and long-term depression (LTD) induced by several doublet stimulation paradigms in the absence of inhibition. Overall, simulation results provide computational evidence for the first time that the switch between the symmetrical and the asymmetrical STDP operational modes is indeed due to GABA inhibition. Furthermore, gamma frequency inhibition and not theta one is responsible for the transition from asymmetry-to-symmetry. The resulted symmetrical STDP profile is centered at+10 ms with two distinct LTD tails at -10 and +40 ms. Finally, the a+symmetry-to-symmetry transition is strongly dependent on the strength (conductance) of inhibition and its relative onset with respect to pre- and postsynaptic spike stimulation. © 2010 Elsevier Ltd.


Fennelly K.P.,University of Florida | Jones-Lopez E.C.,Boston University
Frontiers in Immunology | Year: 2015

Experimental animal models of tuberculosis (TB) have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has traditionally been assessed using microscopy for acid-fast bacilli in the sputum, which should be considered only a risk factor. We have recently demonstrated that cough aerosol cultures from index cases with pulmonary TB are the best predictors of new infection among household contacts. We suggest that cough aerosols of M. tuberculosis are the best surrogates of inhaled dose, and we hypothesize that the quantity of cough aerosols is associated with TB infection versus disease. Although several factors affect the quality of infectious aerosols, we propose that the particle size distribution of cough aerosols is an important predictor of primary upper airway disease and cervical lymphadenitis and of immune responses in exposed hosts. We hypothesize that large droplet aerosols (>5 μ) containing M. tuberculosis deposit in the upper airway and can induce immune responses without establishing infection. We suggest that this may partially explain the large proportion of humans who never develop TB disease in spite of having immunological evidence of M. tuberculosis infection (e.g., positive tuberculin skin test or interferon gamma release assay). If these hypotheses are proven true, they would alter the current paradigm of latent TB infection and reactivation, further demonstrating the need for better biomarkers or methods of assessing TB infection and the risk of developing disease. © 2015 Fennelly and Jones-López.


Risitano A.,Boston University | Beaulieu L.M.,University of Massachusetts Medical School | Vitseva O.,University of Massachusetts Medical School | Freedman J.E.,University of Massachusetts Medical School
Blood | Year: 2012

The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation; however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were cocultured with vascular cells. Coculture of plateletlike particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Posttransfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/ HBG2 and HBA1/HBA2 expression that was directly related to the transfer. Infusion of wild-type platelets into a TLR2- deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, we also observed external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis. © 2012 by The American Society of Hematology.


Stachel J.,Boston University
Living Reviews in Relativity | Year: 2014

This is a historical-critical study of the hole argument, concentrating on the interface between historical, philosophical and physical issues. Although it includes a review of its history, its primary aim is a discussion of the contemporary implications of the hole argument for physical theories based on dynamical, background-independent space-time structures. The historical review includes Einstein's formulations of the hole argument, Kretschmann's critique, as well as Hilbert's reformulation and Darmois' formulation of the general-relativistic Cauchy problem. The 1970s saw a revival of interest in the hole argument, growing out of attempts to answer the question: Why did three years elapse between Einstein's adoption of the metric tensor to represent the gravitational field and his adoption of the Einstein field equations? The main part presents some modern mathematical versions of the hole argument, including both coordinate-dependent and coordinate-independent definitions of covariance and general covariance; and the fiber bundle formulation of both natural and gauge natural theories. By abstraction from continuity and differentiability, these formulations can be extended from differentiable manifolds to any set; and the concepts of permutability and general permutability applied to theories based on relations between the elements of a set, such as elementary particle theories. We are closing with an overview of current discussions of philosophical and physical implications of the hole argument.


Ma N.,University of California at Berkeley | Ishwar P.,Boston University
IEEE Transactions on Information Theory | Year: 2011

A two-terminal interactive distributed source coding problem with alternating messages for function computation at both locations is studied. For any number of messages, a computable characterization of the rate region is provided in terms of single-letter information measures. While interaction is useless in terms of the minimum sum-rate for lossless source reproduction at one or both locations, the gains can be arbitrarily large for function computation even when the sources are independent. For a class of sources and functions, interaction is shown to be useless, even with infinite messages, when a function has to be computed at only one location, but is shown to be useful, if functions have to be computed at both locations. For computing the Boolean AND function of two independent Bernoulli sources at both locations, an achievable infinite-message sum-rate with infinitesimal-rate messages is derived in terms of a 2-D definite integral and a rate-allocation curve. The benefit of interaction is highlighted in multiterminal function computation problem through examples. For networks with a star topology, multiple rounds of interactive coding is shown to decrease the scaling law of the total network rate by an order of magnitude as the network grows. © 2011 IEEE.


Grigoryan L.,Baylor College of Medicine | Trautner B.W.,Houston Center for Innovations in Quality | Trautner B.W.,Baylor College of Medicine | Gupta K.,Boston University
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Urinary tract infection is among the most common reasons for an outpatient visit and antibiotic use in adult populations. The increasing prevalence of antibacterial resistance among community uropathogens affects the diagnosis and management of this clinical syndrome.OBJECTIVES: To define the optimal approach for treating acute cystitis in young healthy women and in women with diabetes and men and to define the optimal approach for diagnosing acute cystitis in the outpatient setting.EVIDENCE REVIEW: Evidence for optimal treatment regimens was obtained by searching PubMed and the Cochrane database for English-language studies published up to July 21, 2014.FINDINGS: Twenty-seven randomized clinical trials (6463 patients), 6 systematic reviews, and 11 observational studies (252 934 patients) were included in our review. Acute uncomplicated cystitis in women can be diagnosed without an office visit or urine culture. Trimethoprimsulfamethoxazole (160/800 mg twice daily for 3 days), nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5-7 days), and fosfomycin trometamol (3 gin a single dose) are all appropriate first-line therapies for uncomplicated cystitis. Fluoroquinolones are effective for clinical outcomes but should be reserved for more invasive infections. β-Lactam agents (amoxicillin-clavulanate and cefpodoxime-proxetil) are not as effective as empirical first-line therapies. Immediate antimicrobial therapy is recommended rather than delayed treatment or symptom management with ibuprofen alone. Limited observational studies support 7 to 14 days of therapy for acute urinary tract infection in men. Based on 1 observational study and our expert opinion, women with diabetes without voiding abnormalities presenting with acute cystitis should be treated similarly to women without diabetes.CONCLUSIONS AND RELEVANCE: Immediate antimicrobial therapy with trimethoprimsulfamethoxazole, nitrofurantoin, or fosfomycin is indicated for acute cystitis in adult women. Increasing resistance rates among uropathogens have complicated treatment of acute cystitis. Individualized assessment of risk factors for resistance and regimen tolerability is needed to choose the optimum empirical regimen. © 2014 American Medical Association. All rights reserved.


Schwab D.J.,Princeton University | Nemenman I.,Emory University | Mehta P.,Boston University
Physical Review Letters | Year: 2014

The joint probability distribution of states of many degrees of freedom in biological systems, such as firing patterns in neural networks or antibody sequence compositions, often follows Zipf's law, where a power law is observed on a rank-frequency plot. This behavior has been shown to imply that these systems reside near a unique critical point where the extensive parts of the entropy and energy are exactly equal. Here, we show analytically, and via numerical simulations, that Zipf-like probability distributions arise naturally if there is a fluctuating unobserved variable (or variables) that affects the system, such as a common input stimulus that causes individual neurons to fire at time-varying rates. In statistics and machine learning, these are called latent-variable or mixture models. We show that Zipf's law arises generically for large systems, without fine-tuning parameters to a point. Our work gives insight into the ubiquity of Zipf's law in a wide range of systems. © 2014 American Physical Society.


Culpepper L.,Boston University
Journal of Clinical Psychiatry | Year: 2010

Primary care clinicians need to move beyond first-line therapy for major depression. While initial treatment is ineffective in about two-thirds of patients, patients who have not responded to such initial treatments can be managed effectively. The severity of depression is as high in primary care as in specialty care settings. The risk of depression is currently elevated because economic hardship, job insecurity, and low socioeconomic status increase the likelihood of depression and treatment resistance. Depression worsens outcomes for medical comorbidities, such as cardiac disease, chronic obstructive pulmonary disease, and diabetes mellitus, and it increases the risk of rehospitalization. When depression is treatment-resistant (generally defined as not responding to 2 courses of treatment of adequate dose and duration), morbidity and mortality are increased, quality of life and function are reduced, and long-term brain changes may occur. Opportunities for change in care are available. Screening for depression in primary care settings with staff-assisted support, adopting the concepts of the patient-centered medical home and stepped care, and using new treatment options such as atypical antipsychotics and other treatment modalities can improve outcomes for these patients. Now is the time to make these moves because new tools, systems, and treatments offer ways to help these patients. © Copyright 2010 Physicians Postgraduate Press, Inc.


Farwell A.P.,Boston University
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2013

PURPOSE OF REVIEW: The current state of the pathophysiology, diagnosis, and therapeutic implications of the nonthyroidal illness syndrome is reviewed. RECENT FINDINGS: Previous studies attributed the development of the nonthyroidal illness syndrome to alterations in three main areas of thyroid hormone metabolism: deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding to serum proteins. New studies suggest that alterations in thyroid hormone transport into tissues and alterations of the nuclear thyroid hormone receptors may also play a role. Therapy of the nonthyroidal illness syndrome remains a controversial topic. SUMMARY: Multiple factors lead to the development of the nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase activity, thyrotropin-releasing hormone and thyroid-stimulating hormone secretion, hormone binding to plasma proteins, thyroid hormone transporter expression and activity, and the thyroid hormone nuclear receptor complex. These data show that acute and chronic illness affect all aspects of thyroid hormone metabolism and action. Some of these changes are physiologic and some are pharmacologic. The mediators of these alterations are still largely unclear. There continues to be no indication for thyroid hormone therapy in the vast majority of patients with the nonthyroidal illness syndrome, although interesting data suggest a possible role for treating a small subset of patients. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Weil D.,Boston University | Graham M.,Harvard University | Fung A.,Harvard University
Science | Year: 2013

Research explores how policy goals might be reached by simply requiring that information be made public.


Boswell J.F.,Boston University
Journal of consulting and clinical psychology | Year: 2013

Although associations with outcome have been inconsistent, therapist adherence and competence continues to garner attention, particularly within the context of increasing interest in the dissemination, implementation, and sustainability of evidence-based treatments. To date, research on therapist adherence and competence has focused on average levels across therapists. With a few exceptions, research has failed to address multiple sources of variability in adherence and competence, identify important factors that might account for variability, or take these sources of variability into account when examining associations with symptom change. (a) statistically demonstrate between- and within-therapist variability in adherence and competence ratings and examine patient characteristics as predictors of this variability and (b) examine the relationship between adherence/competence and symptom change. Method: Randomly selected audiotaped sessions from a randomized controlled trial of cognitive-behavioral therapy for panic disorder were rated for therapist adherence and competence. Patients completed a self-report measure of panic symptom severity prior to each session and the Inventory of Interpersonal Problems-Personality Disorder Scale prior to the start of treatment. Significant between- and within-therapist variability in adherence and competence were observed. Adherence and competence deteriorated significantly over the course of treatment. Higher patient interpersonal aggression was associated with decrements in both adherence and competence. Neither adherence nor competence predicted subsequent panic severity. Variability and "drift" in adherence and competence can be observed in controlled trials. Training and implementation efforts should involve continued consultation over multiple cases in order to account for relevant patient factors and promote sustainability across sessions and patients.


Eichten E.J.,Fermi National Accelerator Laboratory | Lane K.,Boston University | Martin A.,Fermi National Accelerator Laboratory
Physical Review Letters | Year: 2011

We propose that the 3.2σ excess at ∼150GeV in the dijet mass spectrum of W+jets reported by CDF is the technipion πT of low-scale technicolor. Its relatively large cross section is due to production of a narrow Wjj resonance, the technirho, which decays to WπT. We discuss ways to enhance and strengthen the technicolor hypothesis and suggest companion searches at the Tevatron and LHC. © 2011 American Physical Society.


Neupert T.,Paul Scherrer Institute | Santos L.,Harvard University | Chamon C.,Boston University | Mudry C.,Paul Scherrer Institute
Physical Review Letters | Year: 2011

We present a simple prescription to flatten isolated Bloch bands with a nonzero Chern number. We first show that approximate flattening of bands with a nonzero Chern number is possible by tuning ratios of nearest-neighbor and next-nearest-neighbor hoppings in the Haldane model and, similarly, in the chiral-π-flux square lattice model. Then we show that perfect flattening can be attained with further range hoppings that decrease exponentially with distance. Finally, we add interactions to the model and present exact diagonalization results for a small system at 1/3 filling that support (i) the existence of a spectral gap, (ii) that the ground state is a topological state, and (iii) that the Hall conductance is quantized. © 2011 American Physical Society.


Selin H.,Boston University
Global Environmental Politics | Year: 2012

As global environmental governance evolves, the parties to the 1989 Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal and to the 2001 Stockholm Convention on Persistent Organic Pollutants have established regional centers working on capacity building and technology transfer. This article empirically explores the following questions: Why did the parties to the Basel and Stockholm Conventions establish these regional centers? What roles do the regional centers play in treaty implementation and multilevel governance? The article argues that the parties have set up regional centers in response to three partially overlapping sets of developing- and industrialized-country interests: expanding regional cooperation (both developing and industrialized countries); attracting more resources for treaty implementation (mainly developing countries); and supporting implementation projects across smaller groups of countries (mainly industrialized countries). This article finds that the regional centers collectively operate in three broad areas important to treaty implementation: raising awareness, strengthening administrative ability, and diffusing scientific and technical assistance and information. However, the ability of the regional centers to function effectively depends on access to greater resources and stronger political support. There may also be benefits to expanding regional center mandates into areas of monitoring and compliance to improve multilevel governance. Furthermore, the regional level should be given more consideration in the study of global environmental politics. © 2012 by the Massachusetts Institute of Technology.


Fry J.L.,Boston University
Hypertension | Year: 2016

Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM-specific genetic SirT1 overexpression (SMTG) prevented pulse wave velocity increases induced by HFHS feeding, during 8 months. Administration of resveratrol or S17834, 2 polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 overexpression (SirT1 bacterial artificial chromosome overexpressor), without evident metabolic improvements. In addition, HFHS-induced pulse wave velocity increases were reversed by 1-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and vascular cell adhesion molecule (VCAM-1) and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and antioxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome. © 2016 American Heart Association, Inc


Nicotine is widely recognized as an addictive psychoactive drug. Since most smokers are bio-behaviorally addicted, quitting can be very difficult and is often accompanied by withdrawal symptoms. Research indicates that nicotine replacement therapy (NRT) can double quit rates. However, the success rate for quitting remains low. E-cigarettes (electronic cigarettes) are battery-powered nicotine delivery devices used to inhale doses of vaporized nicotine from a handheld device similar in shape to a cigarette without the harmful chemicals present in tobacco products. Anecdotal evidence strongly suggests that e-cigarettes may be effective in helping smokers quit and preventing relapse, but there have been few published qualitative studies, especially among successful e-cigarette users, to support this evidence. Qualitative design using focus groups (N = 11); 9 men and 2 women. Focus groups were conducted by posing open-ended questions relating to the use of e-cigarettes, comparison of effectiveness between NRTs and e-cigarettes, barriers to quitting, and reasons for choosing e-cigarettes over other methods. Five themes emerged that describe users' perceptions of why e-cigarettes are efficacious in quitting smoking: 1) bio-behavioral feedback, 2) social benefits, 3) hobby elements, 4) personal identity, and 5) distinction between smoking cessation and nicotine cessation. Additionally, subjects reported their experiences with NRTs compared with e-cigarettes, citing negative side effects of NRTs and their ineffectiveness at preventing relapse. These findings suggest tobacco control practitioners must pay increased attention to the importance of the behavioral and social components of smoking addiction. By addressing these components in addition to nicotine dependence, e-cigarettes appear to help some tobacco smokers transition to a less harmful replacement tool, thereby maintaining cigarette abstinence.


Opher M.,Boston University | Drake J.F.,University of Maryland University College
Astrophysical Journal Letters | Year: 2013

Based on the difference between the orientation of the interstellar and the solar magnetic fields, there was an expectation by the community that the magnetic field direction will rotate dramatically across the heliopause (HP). Recently, the Voyager team concluded that Voyager 1 (V1) crossed into interstellar space last year. The question is then why there was no significant rotation in the direction of the magnetic field across the HP. Here we present simulations that reveal that strong rotations in the direction of the magnetic field at the HP at the location of V1 (and Voyager 2) are not expected. The solar magnetic field strongly affects the drapping of the interstellar magnetic field (BISM) around the HP. BISM twists as it approaches the HP and acquires a strong T component (East-West). The strong increase in the T component occurs where the interstellar flow stagnates in front of the HP. At this same location the N component BN is significantly reduced. Above and below, the neighboring BISM lines also twist into the T direction. This behavior occurs for a wide range of orientations of B ISM. The angle δ = asin (BN/B) is small (around 10°-20°), as seen in the observations. Only after some significant distance outside the HP is the direction of the interstellar field distinguishably different from that of the Parker spiral. © 2013. The American Astronomical Society. All rights reserved.


Swisdak M.,University of Maryland University College | Drake J.F.,University of Maryland University College | Opher M.,Boston University
Astrophysical Journal Letters | Year: 2013

The picture of the heliopause (HP) - the boundary between the domains of the Sun and the local interstellar medium (LISM) - as a pristine interface with a large rotation in the magnetic field fails to describe recent Voyager 1 (V1) data. Magnetohydrodynamic (MHD) simulations of the global heliosphere reveal that the rotation angle of the magnetic field across the HP at V1 is small. Particle-in-cell simulations, based on cuts through the MHD model at V1's location, suggest that the sectored region of the heliosheath (HS) produces large-scale magnetic islands that reconnect with the interstellar magnetic field while mixing LISM and HS plasma. Cuts across the simulation reveal multiple, anti-correlated jumps in the number densities of LISM and HS particles, similar to those observed, at the magnetic separatrices. A model is presented, based on both the observations and simulations, of the HP as a porous, multi-layered structure threaded by magnetic fields. This model further suggests that contrary to the conclusions of recent papers, V1 has already crossed the HP. © 2013. The American Astronomical Society. All rights reserved..


Thirumalai D.,University of Maryland University College | Reddy G.,University of Maryland University College | Straub J.E.,Boston University
Accounts of Chemical Research | Year: 2012

A variety of neurodegenerative diseases are associated with amyloid plaques, which begin as soluble protein oligomers but develop into amyloid fibrils. Our incomplete understanding of this process underscores the need to decipher the principles governing protein aggregation. Mechanisms of in vivo amyloid formation involve a number of coconspirators and complex interactions with membranes. Nevertheless, understanding the biophysical basis of simpler in vitro amyloid formation is considered important for discovering ligands that preferentially bind regions harboring amyloidogenic tendencies. The determination of the fibril structure of many peptides has set the stage for probing the dynamics of oligomer formation and amyloid growth through computer simulations. Most experimental and simulation studies, however, have been interpreted largely from the perspective of proteins: the role of solvent has been relatively overlooked in oligomer formation and assembly to protofilaments and amyloid fibrils.In this Account, we provide a perspective on how interactions with water affect folding landscapes of amyloid beta (Aβ) monomers, oligomer formation in the Aβ16-22 fragment, and protofilament formation in a peptide from yeast prion Sup35. Explicit molecular dynamics simulations illustrate how water controls the self-assembly of higher order structures, providing a structural basis for understanding the kinetics of oligomer and fibril growth. Simulations show that monomers of Aβ peptides sample a number of compact conformations. The formation of aggregation-prone structures (N*) with a salt bridge, strikingly similar to the structure in the fibril, requires overcoming a high desolvation barrier. In general, sequences for which N* structures are not significantly populated are unlikely to aggregate.Oligomers and fibrils generally form in two steps. First, water is expelled from the region between peptides rich in hydrophobic residues (for example, Aβ16-22), resulting in disordered oligomers. Then the peptides align along a preferred axis to form ordered structures with anti-parallel β-strand arrangement. The rate-limiting step in the ordered assembly is the rearrangement of the peptides within a confining volume.The mechanism of protofilament formation in a polar peptide fragment from the yeast prion, in which the two sheets are packed against each other and create a dry interface, illustrates that water dramatically slows self-assembly. As the sheets approach each other, two perfectly ordered one-dimensional water wires form. They are stabilized by hydrogen bonds to the amide groups of the polar side chains, resulting in the formation of long-lived metastable structures. Release of trapped water from the pore creates a helically twisted protofilament with a dry interface. Similarly, the driving force for addition of a solvated monomer to a preformed fibril is water release; the entropy gain and favorable interpeptide hydrogen bond formation compensate for entropy loss in the peptides.We conclude by offering evidence that a two-step model, similar to that postulated for protein crystallization, must also hold for higher order amyloid structure formation starting from N*. Distinct water-laden polymorphic structures result from multiple N* structures. Water plays multifarious roles in all of these protein aggregations. In predominantly hydrophobic sequences, water accelerates fibril formation. In contrast, water-stabilized metastable intermediates dramatically slow fibril growth rates in hydrophilic sequences. © 2011 American Chemical Society.


Nazer B.,Boston University | Gastpar M.,University of California at Berkeley | Gastpar M.,Technical University of Delft
Proceedings of the IEEE | Year: 2011

When two or more users in a wireless network transmit simultaneously, their electromagnetic signals are linearly superimposed on the channel. As a result, a receiver that is interested in one of these signals sees the others as unwanted interference. This property of the wireless medium is typically viewed as a hindrance to reliable communication over a network. However, using a recently developed coding strategy, interference can in fact be harnessed for network coding. In a wired network, (linear) network coding refers to each intermediate node taking its received packets, computing a linear combination over a finite field, and forwarding the outcome towards the destinations. Then, given an appropriate set of linear combinations, a destination can solve for its desired packets. For certain topologies, this strategy can attain significantly higher throughputs over routing-based strategies. Reliable physical layer network coding takes this idea one step further: using judiciously chosen linear error-correcting codes, intermediate nodes in a wireless network can directly recover linear combinations of the packets from the observed noisy superpositions of transmitted signals. Starting with some simple examples, this paper explores the core ideas behind this new technique and the possibilities it offers for communication over interference-limited wireless networks. © 2006 IEEE.


Tager-Flusberg H.,Boston University
Neural Networks | Year: 2010

Core impairments in social and communicative behaviors are among the defining characteristics of autism spectrum disorder (ASD), making this a model syndrome for investigating the mechanisms that underlie social cognition and behavior. Current research is exploring the origins of social impairments in prospective longitudinal studies of infants who are at high risk for ASD, defined as having an older sibling with the disorder. Behavioral studies that have followed these infants through to outcomes have found that during the early months of life they are no different from typically developing infants; they are socially interested, engaged and enjoy interactions with people. By the end of the first year risk signs for later ASD can be identified though no single marker has been identified. It seems that an aggregate of risk markers together may be needed to predict ASD. Other studies have compared infants at risk for ASD to low risk controls to identify neurocognitive endophenotypes. Several differences in subtle aspects of behavior and in brain organization have been found in infants younger than 12 months, though it is not known whether these differences are also risk markers for a later ASD diagnosis. The findings from these lines of research are used to provide a new view of ASD, as a disorder defined on the basis of alterations in the developmental trajectories across multiple domains. ASD is an emergent disorder that is characterized by the loss of social communication skills in the period between 9 and 24 months. Across children the rate, timing and severity of this loss is highly variable. Future research will lead to a greater understanding of the genetic and neurocognitive mechanisms that underlie these fundamental changes in the developmental patterns of individuals with ASD. © 2010 Elsevier Ltd.


Krapivsky P.L.,Boston University | Mallick K.,CEA Saclay Nuclear Research Center | Sadhu T.,CEA Saclay Nuclear Research Center
Physical Review Letters | Year: 2014

We apply macroscopic fluctuation theory to study the diffusion of a tracer in a one-dimensional interacting particle system with excluded mutual passage, known as single-file diffusion. In the case of Brownian point particles with hard-core repulsion, we derive the cumulant generating function of the tracer position and its large deviation function. In the general case of arbitrary interparticle interactions, we express the variance of the tracer position in terms of the collective transport properties, viz., the diffusion coefficient and the mobility. Our analysis applies both for fluctuating (annealed) and fixed (quenched) initial configurations. © 2014 American Physical Society.


Polkovnikov A.,Boston University | Sengupta K.,Indian Association for The Cultivation of Science | Silva A.,Abdus Salam International Center For Theoretical Physics | Vengalattore M.,Cornell University
Reviews of Modern Physics | Year: 2011

This Colloquium gives an overview of recent theoretical and experimental progress in the area of nonequilibrium dynamics of isolated quantum systems. There is particularly a focus on quantum quenches: the temporal evolution following a sudden or slow change of the coupling constants of the system Hamiltonian. Several aspects of the slow dynamics in driven systems are discussed and the universality of such dynamics in gapless systems with specific focus on dynamics near continuous quantum phase transitions is emphasized. Recent progress on understanding thermalization in closed systems through the eigenstate thermalization hypothesis is also reviewed and relaxation in integrable systems is discussed. Finally key experiments probing quantum dynamics in cold atom systems are overviewed and put into the context of our current theoretical understanding. © 2011 American Physical Society.


Zaman M.H.,Boston University
Nature Reviews Cancer | Year: 2013

In the past decade, novel materials, probes and tools have enabled fundamental and applied cancer researchers to take a fresh look at the complex problem of tumour invasion and metastasis. These new tools, which include imaging modalities, controlled but complex in vitro culture conditions, and the ability to model and predict complex processes in vivo, represent an integration of traditional with novel engineering approaches; and their potential effect on quantitatively understanding tumour progression and invasion looks promising. © 2013 Macmillan Publishers Limited.


Apolipoprotein A-I (apoA-I) is the major protein of plasma high-density lipoproteins (HDLs), macromolecular assemblies of proteins and lipids that remove cell cholesterol and protect against atherosclerosis. HDL heterogeneity, large size (7.7-12 nm), and ability to exchange proteins have prevented high-resolution structural analysis. Low-resolution studies showed that two apoA-I molecules form an antiparallel α-helical "double belt" around an HDL particle. The atomic-resolution structure of the C-terminal truncated lipid-free Δ(185-243)apoA-I, determined recently by Mei and Atkinson, provides unprecedented new insights into HDL structure-function. It allows us to propose a molecular mechanism for the adaptation of the full-length protein to increasing lipid load during cholesterol transport. ApoA-I conformations on small, midsize, and large HDLs are proposed based on the tandem α-helical repeats and the crystal structure of Δ(185-243)apoA-I and are validated by comparison with extensive biophysical data reported by many groups. In our models, the central half of the double belt ("constant" segment 66-184) is structurally conserved while the N- and C-terminal half ("variable" segments 1-65 and 185-243) rearranges upon HDL growth. This includes incremental unhinging of the N-terminal bundle around two flexible regions containing G39 and G65 to elongate the belt, along with concerted swing motion of the double belt around G65-P66 and G185-G186 hinges that are aligned on various-size particles, to confer two-dimensional surface curvature to spherical HDLs. The proposed conformational ensemble integrates and improves several existing HDL models. It helps provide a structural framework necessary to understand functional interactions with over 60 other HDL-associated proteins and, ultimately, improve the cardioprotective function of HDL. © 2012 Elsevier Ltd.


Chakrabarti P.,Boston University
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2015

PURPOSE OF REVIEW: Metabolic diseases, such as type 2 diabetes, cardiac dysfunction, hypertension, and hepatic steatosis, share one critical causative factor: abnormal lipid partitioning, that redistribution of triglycerides from adipocytes to nonadipose peripheral tissues. Lipid overload of these tissues causes a number of pathological effects collectively known as lipotoxicity. If we find the way to correct lipid partitioning, we will restrain metabolic diseases, improve life quality and life expectancy and radically reduce healthcare costs. RECENT FINDINGS: Lipid partitioning in the body is maintained by tightly regulated and balanced rates of de novo lipogenesis, lipolysis, adipogenesis, and mitochondrial oxidation primarily in fat and liver. Recent studies highlighted in this review have established mTOR as a central regulator of lipid storage and metabolism. SUMMARY: Increased activity of mTOR in obesity may compensate for the negative consequences of overnutrition, whereas dysregulation of mTOR may lead to abnormal lipid partitioning and metabolic disease. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Wilson M.R.,Boston University
Current Opinion in Neurology | Year: 2013

Purpose of Review: This review highlights research and development in the field of emerging viral causes of encephalitis over the past year. Recent Findings: There is new evidence for the presence of henipaviruses in African bats. There have also been promising advances in vaccine and neutralizing antibody research against Hendra and Nipah viruses. West Nile virus continues to cause large outbreaks in the United States, and long-term sequelae of the virus are increasingly appreciated. There is exciting new research regarding the variable susceptibility of different brain regions to neurotropic virus infection. Another cluster of solid organ transplant recipients developed encephalitis from organ donor-acquired lymphocytic choriomeningitis virus. The global epidemiology of Japanese encephalitis virus has been further clarified. Evidence continues to accumulate for the central nervous system involvement of dengue virus, and the recent deadly outbreak of enterovirus 71 in Cambodian children is discussed. Summary: In response to complex ecological and societal dynamics, the worldwide epidemiology of viral encephalitis continues to evolve in surprising ways. The articles highlighted here include new research on virus epidemiology and spread, new outbreaks as well as progress in the development of vaccines and therapeutics. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


The associations of long-term patterns of risk factors and the risk of incident atrial fibrillation (AF) are incompletely characterized. Among 4351 Framingham Study participants (mean age 50±11 years at baseline examination, 57% women) from the original and offspring cohorts, we defined longitudinal patterns, referred to as trajectories, of AF risk factors and a composite AF risk score using ≈16 years of data. We used Cox proportional hazards models to examine the association of trajectories to 15-year risk of AF. During follow-up, 719 participants developed AF. Five distinct trajectory groups were identified for systolic blood pressure (BP): groups 1 and 2 (normotensive throughout), group 3 (prehypertensive), group 4 (hypertensive initially with decreasing BP), and group 5 (hypertensive and increasing BP). In multivariable-adjusted analyses, compared with group 1, groups 4 (hazard ratio 2.05; 95% confidence interval 1.24–3.37) and 5 (hazard ratio 1.95; 95% confidence interval 1.08–3.49) were associated with incident AF. Three trajectory groups were identified for antihypertensive treatment. Compared with the group with no treatment throughout, the other 2 groups were associated with increased risk of incident AF. Distinct trajectories for diastolic BP, smoking, diabetes mellitus, and the composite risk score were not associated with increased 15-year risk of AF. Longitudinal trajectories may distinguish how exposures related to AF contribute toward prospective AF risk. Distinct trajectory groups with persistently elevated systolic BP and longer antihypertensive treatment are associated with increased risk of incident AF. © 2016 American Heart Association, Inc


Siggers T.,Boston University | Gordan R.,Duke University
Nucleic Acids Research | Year: 2014

Binding of proteins to particular DNA sites across the genome is a primary determinant of specificity in genome maintenance and gene regulation. DNA-binding specificity is encoded at multiple levels, from the detailed biophysical interactions between proteins and DNA, to the assembly of multi-protein complexes. At each level, variation in the mechanisms used to achieve specificity has led to difficulties in constructing and applying simple models of DNA binding. We review the complexities in protein-DNA binding found at multiple levels and discuss how they confound the idea of simple recognition codes. We discuss the impact of new highthroughput technologies for the characterization of protein-DNA binding, and how these technologies are uncovering new complexities in protein-DNA recognition. Finally, we review the concept of multi-protein recognition codes in which new DNAbinding specificities are achieved by the assembly of multi-protein complexes. © 2013 The Author(s). Published by Oxford University Press.


Linden J.A.,Boston University | Linden J.A.,Boston Medical Center
New England Journal of Medicine | Year: 2011

A 20-year-old woman presents to the emergency department with a report of having been sexually assaulted 24 hours earlier. She reports that a man she had met at a campus party walked her to her apartment, where he assaulted and raped her, including vaginal penetration. She did not report the assault to the police but confided in a friend, who encouraged her to seek medical care. How should this patient be evaluated and treated? Copyright © 2011 Massachusetts Medical Society.


We investigated the pattern of genetic and morphological variation and the timing of diversification in a Neotropical direct developing frog, Pristimantis w-nigrum (Craugastoridae) to gain insight into the historical biogeography of the northern Andes. Phylogenetic inference and analyses of genetic differentiation at mitochondrial and nuclear markers reveal eight mitochondrial clades that display concordant and highly structured nuclear genetic variation along both eastern and western slopes of the Ecuadorian Andes. These eight phylogroups are deeply divergent and show little evidence of change in effective size over substantial periods of time. Consistent with other phylogenetic studies of vertebrates in the Andes, the timing of genetic divergence among lineages coincides with sequential bouts of Andean orogenesis during the late Miocene and early Pliocene. Morphometric analyses recover little morphological variation among populations in spite of considerable genetic divergence. The deep genetic differentiation among populations of P. w-nigrum suggests that this species harbors unrecognized diversity and may represent a complex of cryptic species. These results illuminate the evolutionary processes that generate diversity in tropical montane biomes and underscore the fact that cryptic diversity may be an important component of Neotropical montane biodiversity. Copyright © 2013 Elsevier Inc. All rights reserved.


Shah B.,Boston University
Radiographics : a review publication of the Radiological Society of North America, Inc | Year: 2011

Quantitative magnetic resonance (MR) imaging seeks to quantify fundamental biologic and MR-inducible tissue properties, in contrast to the routine application of MR imaging in the clinic, in which differences in MR parameters are used to generate contrast for subsequent subjective image analysis. Fundamental parameters that are commonly quantified by using MR imaging include proton density, diffusion, T1 relaxation, T2 and T2* relaxation, and magnetization transfer. Applications of these MR imaging-quantifiable parameters to abdominal imaging include oncologic imaging, evaluation of diffuse liver disease, and assessment of splenic, renal, and pancreatic disease. An understanding of the inherent physical principles underlying the basic quantitative parameters as well as the commonly used pulse sequences requisite to their derivation is critical, as this field is rapidly growing and its use will likely continue to expand in the clinic. The full potential of quantitative MR imaging applied to abdominal imaging has yet to be realized, but the myriad applications reported to date will undoubtedly continue to grow. Copyright © RSNA, 2011.


Dooms H.,Boston University
Journal of Autoimmunity | Year: 2013

Interleukin-7 (IL-7) is a critical survival factor for lymphocytes and recent studies suggest targeting the IL-7/IL-7Rα pathway holds promise for the treatment of autoimmune diseases. Several lines of evidence, genetic as well as functional, indicate an important role for this cytokine in autoimmune inflammation: polymorphisms in the IL-7Rα have been associated with increased risk for autoimmune disease and blocking IL-7/IL-7Rα with antibodies showed therapeutic efficacy in several autoimmune mouse models. Insights are starting to emerge about the mechanisms underlying IL-7's role in autoimmunity and tolerance, revealing surprising novel functions beyond its traditional activity as a T cell survival factor. In the first part of this review, the functions of IL-7 in the immune system are concisely described, providing a basis for understanding their potential role in promoting autoimmune responses. In the second part, current knowledge about the role of IL-7 in various autoimmune conditions is reviewed. © 2013 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.


Neilsen J.,Boston University
Advances in Space Research | Year: 2013

In the last decade, high-resolution X-ray spectroscopy has revolutionized our understanding of the role of accretion disk winds in black hole X-ray binaries. Here I present a brief review of the state of wind studies in black hole X-ray binaries, focusing on recent arguments that disk winds are not only extremely massive, but also highly variable. I show how new and archival observations at high timing and spectral resolution continue to highlight the intricate links between the inner accretion flow, relativistic jets, and accretion disk winds. Finally, I discuss methods to infer the driving mechanisms of observed disk winds and their implications for connections between mass accretion and ejection processes. © 2013 COSPAR. Published by Elsevier Ltd. All rights reserved.


Schmidt C.A.,Boston University
Journal of Geophysical Research: Space Physics | Year: 2013

Ground-based observations and MESSENGER's first flyby show persistent asymmetries in Mercury's neutral sodium tail, with brightest emission often seen in the northern lobe. This feature may be associated with the recent finding that the magnetic dipole moment is offset from the planet's center by 0.2 R M to the north, while approximately aligned with the spin axis. Such a configuration produces an asymmetry in the magnetosphere cusp whereby more plasma has direct access to the planet's southern hemisphere than the north. Using 3-D numerical modeling, it is demonstrated that ion precipitation, enhanced in the south, can result in the observed Na emission profiles across the tail that are brighter to the north. However, sources located at high-latitude cusp footprints on the dayside are unable to match the observed width of the brightness profiles across the tail. Instead, these simulations provide evidence for lower latitude sources on the dawnside, resulting from the accumulation of sodium during the long Mercury night. Photodesorption, rather than ion sputtering, is determined to be the responsible mechanism for this population's release and escape from the planet's surface. ©2013. American Geophysical Union. All Rights Reserved.


D'Alessio L.,Pennsylvania State University | D'Alessio L.,Boston University | Rigol M.,Pennsylvania State University
Nature Communications | Year: 2015

Realizing topological insulators is of great current interest because of their remarkable properties and possible future applications. There are recent proposals based on Floquet analyses that one can generate topologically non-trivial insulators by periodically driving topologically trivial ones. Here we address what happens if one follows the dynamics in such systems. Specifically, we present an exact study of the time evolution of a graphene-like system subjected to a circularly polarized electric field. We prove that for infinite (translationally invariant) systems the Chern number is conserved under unitary evolution. For systems with boundaries, on the other hand, we show that a properly defined topological invariant, the Bott index, can change. Hence, it should be possible to experimentally prepare topological states starting from non-topological ones. We show that the chirality of the edge current in such systems can be controlled by adjusting the filling. © 2015 Macmillan Publishers Limited. All rights reserved.


The relationship between testosterone, well-being and mood is poorly understood. We investigated the effect of testosterone supplementation on mood, well-being, and self-reported health in men with erectile dysfunction (ED) and low serum testosterone levels. This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov registration number NCT00512707), in which 140 men, 40-70 years, with ED and low serum testosterone levels were first optimized on sildenafil alone for 3-7 weeks and then randomized to receive either sildenafil plus testosterone gel (n = 70) or sildenafil plus placebo (n = 70) gel for 14 weeks. Using multiple imputations and generalized linear regression, we compared psychological changes in well-being, evaluated by the Psychological General Well-Being Index, and mood, evaluated by Derogatis Affects Balance Scale. Mood and well-being scores were similar between the two groups at baseline and did not substantially change during the administration of sildenafil or after randomization to testosterone. Our findings show that the addition of testosterone to sildenafil in men with ED and low serum testosterone levels was not associated with improvement in either well-being or mood. © 2013 American Society of Andrology and European Academy of Andrology.


Cherici C.,Boston University
Journal of vision | Year: 2012

During visual fixation, microscopic eye movements shift the image on the retina over a large number of photoreceptors. Although these movements have been investigated for almost a century, the amount of retinal image motion they create remains unclear. Currently available estimates rely on assumptions about the probability distributions of eye movements that have never been tested. Furthermore, these estimates were based on data collected with only a few, highly experienced and motivated observers and may not be representative of the instability of naive and inexperienced subjects in experiments that require steady fixation. In this study, we used a high-resolution eye-tracker to estimate the probability distributions of gaze position in a relatively large group of human observers, most of whom were untrained, while they were asked to maintain fixation at the center of a uniform field in the presence/absence of a fixation marker. In all subjects, the probability distribution of gaze position deviated from normality, the underlying assumption of most previous studies. The resulting fixational dispersion of gaze was much larger than previously reported and varied greatly across individuals. Unexpectedly, the precision by which different observers maintained fixation on the marker was best predicted by the properties of ocular drift rather than those of microsaccades. Our results show that, during fixation, the eyes move by larger amounts and at higher speeds than commonly assumed and highlight the importance of ocular drift in maintaining accurate fixation.


McGeeney B.E.,Boston University
Headache | Year: 2013

Hallucinogens and most cannabinoids are classified under schedule 1 of the Federal Controlled Substances Act 1970, along with heroin and ecstacy. Hence they cannot be prescribed by physicians, and by implication, have no accepted medical use with a high abuse potential. Despite their legal status, hallucinogens and cannabinoids are used by patients for relief of headache, helped by the growing number of American states that have legalized medical marijuana. Cannabinoids in particular have a long history of use in the abortive and prophylactic treatment of migraine before prohibition and are still used by patients as a migraine abortive in particular. Most practitioners are unaware of the prominence cannabis or "marijuana" once held in medical practice. Hallucinogens are being increasingly used by cluster headache patients outside of physician recommendation mainly to abort a cluster period and maintain quiescence for which there is considerable anecdotal success. The legal status of cannabinoids and hallucinogens has for a long time severely inhibited medical research, and there are still no blinded studies on headache subjects, from which we could assess true efficacy. © 2012 American Headache Society.


Swartz K.,Boston University
Annual Review of Public Health | Year: 2013

The rapid aging of OECD country populations and the now five-year-long financial crisis in Europe are causing many OECD countries to reconfigure their assistance programs for the elderly, particularly their long-term care (LTC) policies. Debates about intergenerational responsibilities are evident in recently published research papers that examine how countries are revising programs for the elderly. Building financial sustainability into program reforms has suddenly become a priority. Until just recently, reform efforts focused on creating efficiencies and better quality of services. What emerges from the recent literature is a strong sense that the OECD countries are responding to the financial crisis and the rapid aging of populations in very similar ways. Given the countries' different histories of how they provide assistance to their elderly citizens, the convergence of policy responses is not something we might have foreseen. The United States could learn much from the OECD countries' choices. © 2013 by Annual Reviews. All rights reserved.


Williams D.R.,Boston University
Journal of health and social behavior | Year: 2010

This article provides an overview of the contribution of sociologists to the study of racial and ethnic inequalities in health in the United States. It argues that sociologists have made four principal contributions. First, they have challenged and problematized the biological understanding of race. Second, they have emphasized the primacy of social structure and context as determinants of racial differences in disease. Third, they have contributed to our understanding of the multiple ways in which racism affects health. Finally, sociologists have enhanced our understanding of the ways in which migration history and status can affect health. Sociological insights on racial disparities in health have important implications for the development of effective approaches to improve health and reduce health inequities.


Vogt B.A.,Cingulum NeuroSciences Institute | Vogt B.A.,Boston University | Paxinos G.,University of New South Wales
Brain Structure and Function | Year: 2014

A gulf exists between cingulate area designations in human neurocytology and those used in rodent brain atlases with a major underpinning of the former being midcingulate cortex (MCC). The present study used images extracted from the Franklin and Paxinos mouse atlas and Paxinos and Watson rat atlas to demonstrate areas comprising MCC and modifications of anterior cingulate (ACC) and retrosplenial cortices. The laminar architecture not available in the atlases is also provided for each cingulate area. Both mouse and rat have a MCC with neurons in all layers that are larger than in ACC and layer Va has particularly prominent neurons and reduced neuron densities. An undifferentiated ACC area 33 lies along the rostral callosal sulcus in rat but not in mouse and area 32 has dorsal and ventral subdivisions with the former having particularly large pyramidal neurons in layer Vb. Both mouse and rat have anterior and posterior divisions of retrosplenial areas 29c and 30, although their cytology is different in rat and mouse. Maps of the rodent cingulate cortices provide for direct comparisons with each region in the human including MCC and it is significant that rodents do not have a posterior cingulate region composed of areas 23 and 31 like the human. It is concluded that rodents and primates, including humans, possess a MCC and this homology along with those in ACC and retrosplenial cortices permit scientists inspired by human considerations to test hypotheses on rodent models of human diseases. © 2012 Springer-Verlag Berlin Heidelberg.


Holick M.F.,Boston University
Anti-cancer agents in medicinal chemistry | Year: 2013

It has been more than 100 years when it was first appreciated that increased sun exposure reduced risk of dying of cancer. The most beneficial effect of sun exposure is the production of vitamin D in the skin. Recent evidence suggests that most cells in the body not only have a vitamin D receptor but also have the capacity to convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Once formed 1,25-dihydroxyvitamin D can inhibit cellular proliferation, induce cellular maturation, inhibit angiogenesis and ultimately cause apoptosis to prevent malignancy. A multitude of studies have associated improved vitamin D status with decreased risk for developing several deadly cancers including colon, breast, pancreatic and ovarian cancers. Patients with cancer are at high risk for vitamin D deficiency. Sensible sun exposure, vitamin D fortification and vitamin D supplementation should be encouraged to improve the vitamin D status of children and adults not only for bone health but for reducing risk of developing and dying of cancer. The goal is to achieve a blood level of 25-hydroxyvitamin D of 40-60 ng/mL. This can be accomplished by children taking 600-1000 and adults 1500-2000 international units (IU) vitamin D daily from diet and supplements along with sensible sun exposure when the sun is capable of producing vitamin D in the skin.


Dwyer D.J.,University of Maryland University College | Collins J.J.,Howard Hughes Medical Institute | Collins J.J.,Harvard University | Collins J.J.,Boston University | Walker G.C.,Massachusetts Institute of Technology
Annual Review of Pharmacology and Toxicology | Year: 2015

We face an impending crisis in our ability to treat infectious disease brought about by the emergence of antibiotic-resistant pathogens and a decline in the development of new antibiotics. Urgent action is needed. This review focuses on a less well-understood aspect of antibiotic action: the complex metabolic events that occur subsequent to the interaction of antibiotics with their molecular targets and play roles in antibiotic lethality. Independent lines of evidence from studies of the action of bactericidal antibiotics on diverse bacteria collectively suggest that the initial interactions of drugs with their targets cannot fully account for the antibiotic lethality and that these interactions elicit the production of reactive oxidants including reactive oxygen species that contribute to bacterial cell death. Recent challenges to this concept are considered in the context of the broader literature of this emerging area of research. Possible ways that this new knowledge might be exploited to improve antibiotic therapy are also considered. ©2015 by Annual Reviews. All rights reserved.


Andersson S.B.,Boston University
Applied Physics B: Lasers and Optics | Year: 2011

We describe an algorithm for using a confocal microscope for tracking single fluorescent particles diffusing in three dimensions. The algorithm uses a standard confocal setup and directly translates each fluorescence measurement into an actuator command. Through physical simulations, we illustrate 3-D tracking in both stage scanning and beam scanning confocal systems. The simulated stage scanning system achieved tracking of particles diffusing in 3-D with coefficients up to 0.2 μm 2/s when the average fluorescence intensities was less than 1.84 counts per measurement cycle (corresponding to less than 18,400 counts per second) in the presence of background fluorescence with a rate of 5,000 counts per second. Increasing the fluorescence intensity to approximately 193 counts per measurement cycle (1,930,000 counts per second) allowed the system to track up to particles diffusing with coefficients as large as 0.7 μm 2/s. The beam steering system allowed for faster motion of the focal volume of the microscope and successfully tracked particles diffusing with coefficients up to 0.7 μm 2/s with fluorescence measurement intensities of approximately 0.189 counts per measurement cycle (37,570 counts per second) and with coefficients up to 90 μm 2/s when the fluorescence intensity was increased to 19 counts per measurement cycle (3,807,500 counts/sec). © 2011 Springer-Verlag.


Lascaris E.,Boston University
Physical Review Letters | Year: 2016

Recently, it was shown that the Woodcock-Angell-Cheeseman model for liquid silica [L. V. Woodcock, C. A. Angell, and P. Cheeseman, J. Chem. Phys. 65, 1565 (1976)] is remarkably close to having a liquid-liquid critical point (LLCP). We demonstrate that increasing the ion charge separates the global maxima of the response functions, while reducing the charge smoothly merges them into a LLCP, a phenomenon that might be experimentally observable with charged colloids. An analysis of the Si and O coordination numbers suggests that a sufficiently low Si/O coordination number ratio is needed to attain a LLCP. © 2016 American Physical Society.


Hamilton J.A.,Boston University
Biochimica et Biophysica Acta - General Subjects | Year: 2013

Background The molecular details of fatty acid (FA) interactions with albumin are fundamental to understanding transport in the plasma and cellular utilization of these key nutrients and building blocks of membranes. Scope of review This review focuses on the development and application of NMR methods to study FA binding to albumin [bovine (BSA) and human (HSA)]. The key strategy was to use 13C enrichment of a specific carbon in the FA as a non-perturbing probe to permit visualization of the small ligand complexed to the very large protein. NMR contributions to illuminating molecular interactions and FA dynamics are summarized from three decades of studies. Major conclusions Our early studies detected multiple binding sites that we hypothesized were distinguished because of the unique tertiary structure of the protein in close proximity to the FA labeled carbon in each site. Later crystallographic structures revealed the presence of polar and charged amino acid side chains near the carboxyl carbon of the FA and unique tertiary structures lining all of the FA binding pockets. In collaboration with the crystallography group, several FA sites in the crystalline state were matched with NMR resonances in the solution state. With the newest application of NMR, 2D NMR spectroscopy detected nine binding sites, and three were located in the crystal structure through displacement of drugs with identified sites. General significance NMR spectroscopy utilizing the FA as a probe allows characterization of site-specific interactions, molecular motions within binding sites, the order of filling and removal of FA from sites. This article is part of a Special Issue entitled Serum Albumin. © 2013 Elsevier B.V.


Andreasson K.,Lund University | Andreasson K.,Skane University Hospital | Andreasson K.,Boston University
Annals of the rheumatic diseases | Year: 2014

OBJECTIVES: To estimate the prevalence and incidence of systemic sclerosis (SSc) in southern Sweden.METHODS: In Skåne, the southernmost region of Sweden (total population 1.2 million), healthcare provided is registered in the Skåne Healthcare Register. We identified all Skåne residents who had received an International Classification of Diseases 10 diagnosis of SSc (M34) or Raynaud's phenomenon (I73.0) between 1998 and 2010. Every single case was ascertained by review of medical records in reference to the 1980 American Rheumatism Association preliminary classification criteria for SSc and the proposed American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria presented at the ACR/Association of Rheumatology Health Professionals Annual Meeting 2012. We calculated the point prevalence by the end of 2010 by linkage with the population register to exclude deceased persons and we also estimated the mean annual cumulative incidence for 2006-2010.RESULTS: Using the 1980 ARA criteria, the adult prevalence and annual incidence of SSc in the Skåne region were 235 and 14 per 1 million inhabitants respectively. Applying the proposed ACR-EULAR criteria, the corresponding figures were 305 and 19 per 1 million inhabitants. A majority (82%) of the prevalent cases had the limited cutaneous SSc subtype.CONCLUSIONS: The prevalence and incidence of SSc in southern Sweden, based on the 1980 ARA criteria, are higher than previously reported in northern Europe and do not support the concept of a north-south gradient of SSc occurrence in Europe. Application of the proposed ACR-EULAR classification criteria in this population results in about 30-40% higher estimates of SSc prevalence and incidence compared to the 1980 ARA criteria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.


Willett W.C.,Boston University | Willett W.C.,Harvard University | Stampfer M.J.,Chronic Disease Epidemiology Unit | Stampfer M.J.,Harvard University
Annual Review of Public Health | Year: 2013

Large nutritional epidemiology studies, with long-term follow-up to assess major clinical end points, coupled with advances in basic science and clinical trials, have led to important improvements in our understanding of nutrition in primary prevention of chronic disease. Although much work remains, sufficient evidence has accrued to provide solid advice on healthy eating. Good data now support the benefits of diets that are rich in plant sources of fats and protein, fish, nuts, whole grains, and fruits and vegetables; that avoid partially hydrogenated fats; and that limit red meat and refined carbohydrates. The simplistic advice to reduce all fat, or all carbohydrates, has not stood the test of science; strong evidence supports the need to consider fat and carbohydrate quality and different protein sources. This article briefly summarizes major findings from recent years bearing on these issues. © 2013 by Annual Reviews. All rights reserved.


Freddo T.F.,Boston University
Progress in Retinal and Eye Research | Year: 2013

This review traces the evolution of the concept of the blood-aqueous barrier (BAB) during the past 20 years. The Classical model simply stipulated that the tight junctions of the iris vasculature and ciliary epithelium excluded plasma proteins from the aqueous humor (AH). It failed to reconcile the presence of AH protein levels equal to 1% of that found in plasma. Moreover, models of barrier kinetics assumed that the processes of AH secretion and plasma protein entry were directly linked. Thus, elevations of AH protein levels could only be explained by a pathological breakdown of the BAB. Over the last 20 years it has been shown that the plasma proteins in normal AH by-pass the posterior chamber entirely. Instead, these proteins diffuse from the capillaries of ciliary body stroma, into the iris stroma and then into the anterior chamber. This creates a reservoir of plasma-proteins in the iris stroma that is not derived from the iris vessels. This reservoir is prevented from diffusing posteriorly by tight junctions in the posterior iris epithelium. The one-way valve created by the pupil resting on the anterior lens capsule, combined with the continuous, forward flow of AH through the pupil, prevents protein reflux into the posterior chamber. Importantly, in the new paradigm, secretion of AH and the entry of plasma proteins into AH, are semi-independent events. This opens the possibility that AH protein levels could increase in the absence of breakdown of the BAB. Clinical consequences of this new paradigm of the BAB are discussed. © 2012 Elsevier Ltd.


Wetzler L.M.,Boston University
Future Microbiology | Year: 2010

Neisseria meningitidis is a Gram-negative pathogenic bacteria responsible for bacterial meningitis and septicemia. Porins are the most represented outer membrane proteins in the pathogenic Neisseria species, functioning as pores for the exchange of ions, and are characterized by a trimeric -barrel structure. Neisserial porins have been shown to act as adjuvants in the immune response via activation of B cells and other antigen-presenting cells. Their effect on the immune response is mediated by upregulation of the costimulatory molecule B7-2 (CD86) on the surface of antigen-presenting cells, an effect that is dependent on Toll-like receptor (TLR)2 and MyD88, through a cascade of signal transduction events mediated by direct binding of the porin to the TLR2-TLR1 heterodimer. This article summarizes work carried out investigating the mechanisms of the immune stimulating capacity of the neisserial porins (specifically meningococcal PorB), emphasizing cellular events involved in antigen-presenting cell activation and induction of expression of cell surface molecules involved in the immune response. © 2010 Future Medicine Ltd.


Qazi T.M.,Boston University
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Serrated polyps compromise both typical hyperplastic polyps as well as sessile serrated adenomas and dysplastic serrated polyps. Hyperplastic polyps exhibit two histological patterns: microvesicular hyperplastic polyps (MVHPs) and goblet cell hyperplastic polyps (GCHPs). MVHPs and GCHPs differ in their molecular signature. MVHPs have been frequently found to have the BRAFV600E mutation as well as aberrant methylation. In contrast, GCHPs have been associated with the KRAS mutation (KRAS-mut), which are infrequently seen in dysplastic serrated sessile adenomas. The particular risk factors that are associated with development of the types of hyperplastic polyps have not been previously studied. The purpose of this study is to characterize the associations between particular risk factors and the development of goblet cell or microvesicular hyperplastic polyps.METHODS:We conducted a cross-sectional analysis of 3,543 asymptomatic, mostly average risk patients 50 and 79 years of age undergoing open-access screening colonoscopy between March 2005 and January 2012. Each patient was given a survey regarding 25 reputed risk factors for colorectal neoplasia and the responses were correlated with findings at colonoscopy. Associations between putative risk factors for colorectal neoplasia and MVHPs and GSHPs were examined using multiple logistic regression.RESULTS:MVHPS and GCHPs were identified in 5.3% and 8.7% of patients, respectively. The results of the statistical analysis indicate that a history of smoking greater than 20 years is associated with an increased risk of MVHPs (P<0.005) and GCHPs (P<0.005). An elevated BMI >30 kg/m2 was also associated with the presence of MVHP at colonoscopy (P<0.005). Blacks and Asians appear to be protected from the development of MVHPs. In contrast, there was a positive association with the presence of GCHP at colonoscopy in blacks.CONCLUSIONS:The study suggests that the development of the distinct histological types of hyperplastic polyps are associated with distinct modifiable and non-modifiable lifestyle factors.Am J Gastroenterol advance online publication, 28 October 2014; doi:10.1038/ajg.2014.325. © 2014 American College of Gastroenterology


Hu Z.,Boston University
Nucleic acids research | Year: 2013

With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs. With improved understanding of the mechanisms of complex diseases and drug actions through network analysis, novel drug methods (e.g., drug repositioning, multi-target drug and combination therapy) can be designed. More specifically, the new update includes (i) integrated search and navigation of disease and drug hierarchies; (ii) integrated disease-gene, therapy-drug and drug-target association to aid the network construction and filtering; (iii) annotation of genes/drugs using disease/therapy information; (iv) prediction of associated diseases/therapies for a given set of genes/drugs using enrichment analysis; (v) network transformation to support construction of versatile network of drugs, genes, diseases and therapies; (vi) enhanced user interface using docking windows to allow easy customization of node and edge properties with build-in legend node to distinguish different node type. VisANT is freely available at: http://visant.bu.edu.


Davis A.D.,Boston University
The American journal of sports medicine | Year: 2010

BACKGROUND: To address persisting controversy in the literature concerning the efficacy of arthroscopic compared to open acromioplasty, a meta-analysis was performed to evaluate the treatment effect after both approaches. HYPOTHESIS: The final clinical outcomes will be the same after both open and arthroscopic acromioplasty. However, the arthroscopic technique results in faster recovery and less postoperative morbidity as reflected by faster return to work and decreased hospital stays. STUDY DESIGN: Meta-analysis; Level of evidence, 3. METHODS: We performed our search of published English language literature using PubMed. We also searched the proceedings from 4 major orthopaedic meetings convened from 2000 to 2007. Furthermore, the reference sections of all relevant articles were reviewed for pertinent studies and presentations. Nine studies met the inclusion criteria that directly compared arthroscopic versus open acromioplasty with minimum follow-up of 1 year. The analysis focused on 1-year clinical outcome and included comparison of the objective 100-point score, hospital stay, time until return to work, operative time, and complications. RESULTS: No significant differences were found in clinical outcomes or complications for the 2 groups. However, open acromioplasty was associated with longer hospital stays (2.3 days, P = .05) and a greater length in time until return to work (65.1 days) compared with the arthroscopic technique (48.6 days) (P < .05). CONCLUSION: Arthroscopic and open acromioplasty have equivalent ultimate clinical outcomes, operative times, and low complication rates. However, arthroscopic acromioplasty results in faster return to work and fewer hospital inpatient days compared with the open technique.


Mizock L.,Boston University
Psychiatric rehabilitation journal | Year: 2012

This article contrasts the traditional medical approach and size acceptance perspectives on obesity among people with serious mental illnesses. Higher incidences of obesity among populations with serious mental illnesses have been identified. In response, a recent initiative in mental health has urged providers to address the obesity rates among populations with mental illnesses by monitoring weight, prescribing weight loss medication, and recommending bariatric surgery. However, literature is emerging with regards to the double stigma experienced by individuals with obesity and a mental illness. Therefore, the traditional focus on weight loss can benefit from a size acceptance approach to focus on health promotion and avoid stigmatizing size. Citations of theoretical and behavioral health literature on the experiences of individuals with mental illnesses and obesity are presented. Recommendations for interventions, training, and future research related to obesity and mental illnesses are provided. Implications are suggested for a size acceptance approach to interventions for individuals in recovery from mental illnesses to promote health at every size within mental health and medical settings.


Detavernier C.,Ghent University | Dendooven J.,Ghent University | Pulinthanathu Sree S.,Catholic University of Leuven | Ludwig K.F.,Boston University | Martens J.A.,Catholic University of Leuven
Chemical Society Reviews | Year: 2011

Atomic layer deposition (ALD) is a cyclic process which relies on sequential self-terminating reactions between gas phase precursor molecules and a solid surface. The self-limiting nature of the chemical reactions ensures precise film thickness control and excellent step coverage, even on 3D structures with large aspect ratios. At present, ALD is mainly used in the microelectronics industry, e.g. for growing gate oxides. The excellent conformality that can be achieved with ALD also renders it a promising candidate for coating porous structures, e.g. for functionalization of large surface area substrates for catalysis, fuel cells, batteries, supercapacitors, filtration devices, sensors, membranes etc. This tutorial review focuses on the application of ALD for catalyst design. Examples are discussed where ALD of TiO2 is used for tailoring the interior surface of nanoporous films with pore sizes of 4-6 nm, resulting in photocatalytic activity. In still narrower pores, the ability to deposit chemical elements can be exploited to generate catalytic sites. In zeolites, ALD of aluminium species enables the generation of acid catalytic activity. © 2011 The Royal Society of Chemistry.


Scammell M.K.,Boston University
Environmental Health Perspectives | Year: 2010

Background: Recent articles have advocated for the use of qualitative methods in environmental health research. Qualitative research uses nonnumeric data to understand people's opinions, motives, understanding, and beliefs about events or phenomena. Objective: In this analysis of the literature, I report the use of qualitative methods and data in the study of the relationship between environmental exposures and human health. Data sources: A primary search on ISI Web of Knowledge/Web of Science for peer-reviewed journal articles dated from 1991 through 2008 included the following three terms: qualitative, environ*, and health. Inclusion and exclusion criteria are described.D ata extraction: Searches resulted in 3,155 records. Data were extracted and findings of articles analyzed to determine where and by whom qualitative environmental health research is conducted and published, the types of methods and analyses used in qualitative studies of environmental health, and the types of information qualitative data contribute to environmental health. Data synthesis: Ninety-one articles met inclusion criteria. These articles were published in 58 different journals, with a maximum of eight for a single journal. The results highlight a diversity of disciplines and techniques among researchers who used qualitative methods to study environmental health, with most studies relying on one-on-one interviews. Details of the analyses were absent from a large number of studies. Nearly all of the studies identified increased scientific understanding of lay perceptions of environmental health exposures. Discussion and conclusions: Qualitative data are published in traditionally quantitative environmental health studies to a limited extent. However, this analysis demonstrates the potential of qualitative data to improve understanding of complex exposure pathways, including the influence of social factors on environmental health, and health outcomes.


Aral S.,New York University | Dellarocas C.,Boston University | Godes D.,University of Maryland University College
Information Systems Research | Year: 2013

Social media are fundamentally changing the way we communicate, collaborate, consume, and create. They represent one of the most transformative impacts of information technology on business, both within and outside firm boundaries. This special issue was designed to stimulate innovative investigations of the relationship between social media and business transformation. In this paper we outline a broad research agenda for understanding the relationships among social media, business, and society. We place the papers comprising the special issue within this research framework and identify areas where further research is needed. We hope that the flexible framework we outline will help guide future research and develop a cumulative research tradition in this area. © 2013 INFORMS.


Crema M.D.,Boston University
Radiographics : a review publication of the Radiological Society of North America, Inc | Year: 2011

Magnetic resonance (MR) imaging is the most important imaging modality for the evaluation of traumatic or degenerative cartilaginous lesions in the knee. It is a powerful noninvasive tool for detecting such lesions and monitoring the effects of pharmacologic and surgical therapy. The specific MR imaging techniques used for these purposes can be divided into two broad categories according to their usefulness for morphologic or compositional evaluation. To assess the structure of knee cartilage, standard spin-echo (SE) and gradient-recalled echo (GRE) sequences, fast SE sequences, and three-dimensional SE and GRE sequences are available. These techniques allow the detection of morphologic defects in the articular cartilage of the knee and are commonly used in research for semiquantitative and quantitative assessments of cartilage. To evaluate the collagen network and proteoglycan content in the knee cartilage matrix, compositional assessment techniques such as T2 mapping, delayed gadolinium-enhanced MR imaging of cartilage (or dGEMRIC), T1ρ imaging, sodium imaging, and diffusion-weighted imaging are available. These techniques may be used in various combinations and at various magnetic field strengths in clinical and research settings to improve the characterization of changes in cartilage. RSNA, 2011


Robert Horsburgh Jr. C.,Boston University
European Respiratory Review | Year: 2014

This article reviews the published literature on tuberculosis from September 2012 to August 2013 and describes important advances in tuberculosis epidemiology, microbiology, pathology, clinical pharmacology, genetics, treatment and prevention. © ERS 2014.


Galectin-3 (GAL-3), a β-galactoside-binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure (HF). Plasma GAL-3 is inversely related to renal function. It is not known whether the relationship between renal function and GAL-3 is influenced by clinical decompensation, type of HF, or the presence or absence of clinical HF. Patients were prospectively categorized as having acute decompensated HF or stable HF on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma GAL-3 was measured by enzyme-linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL-3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) (P<0.001 versus controls for both) but did not differ between acute decompensated HF and stable HF (P=0.75). Likewise, GAL-3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (P<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (P=0.37). GAL-3 correlated strongly with estimated glomerular filtration rate, both in patients with HF (r=-0.75, P<0.001) and in patients without HF (r=-0.82, P<0.001), and this relationship was unaffected by the presence or absence of clinical HF. Plasma GAL-3 is inversely related to renal function in patients with and without clinical HF. Concentrations of plasma GAL-3 do not seem to depend on the level of compensation or type of HF. Furthermore, the relationship between GAL-3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF.


DeSilva J.M.,Boston University | Devlin M.J.,Beth Israel Deaconess Medical Center
Journal of Human Evolution | Year: 2012

This study tested the hypothesis that talar trabecular microarchitecture reflects the loading patterns in the primate ankle joint, to determine whether talar trabecular morphology might be useful for inferring locomotor behavior in fossil hominins. Trabecular microarchitecture was quantified in the anteromedial, anterolateral, posteromedial, and posterolateral quadrants of the talar body in humans and non-human primates using micro-computed tomography. Trabecular bone parameters, including bone volume fraction, trabecular number and thickness, and degree of anisotropy differed between primates, but not in a manner entirely consistent with hypotheses derived from locomotor kinematics. Humans have highly organized trabecular struts across the entirety of the talus, consistent with the compressive loads incurred during bipedal walking. Chimpanzees possess a high bone volume fraction, consisting of plate-like trabecular struts. Orangutan tali are filled with a high number of thin, connected trabeculae, particularly in the anterior portion of the talus. Gorillas and baboons have strikingly similar internal architecture of the talus. Intraspecific analyses revealed no regional differences in trabecular architecture unique to bipedal humans. Of the 22 statistically significant regional differences in the human talus, all can also be found in other primates. Trabecular thickness, number, spacing, and connectivity density had the same regional relationship in the talus of humans, chimpanzees, gorillas, and baboons, suggesting a deeply conserved architecture in the primate talus. . Australopithecus tali are human-like in most respects, differing most notably in having more oriented struts in the posteromedial quadrant of the body compared with the posterolateral quadrant. Though this result could mean that australopiths loaded their ankles in a unique manner during bipedal gait, the regional variation in degree of anisotropy was similar in humans, chimpanzees, and gorillas. These results collectively suggest that the microarchitecture of the talus does not simply reflect the loading environment, limiting its utility in reconstructing locomotion in fossil primates. © 2012 Elsevier Ltd.


Colson Y.L.,Brigham and Womens Hospital | Grinstaff M.W.,Boston University
Advanced Materials | Year: 2012

Responsive nanoparticles that release their drug cargo in accordance with a change in pH or oxidative stress are of signifi cant clinical interest as this approach offers the opportunity to link drug delivery to a specifi c location or disease state. This research news article reviews the current state of this fi eld by examining a series of published articles that highlight the novelty and benefi ts of using responsive polymeric particles to achieve functionally-targeted drug delivery. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Holick M.F.,Boston University
Public Health Reviews | Year: 2010

Early in the twentieth century more than 80 percent of children in industrialized Europe and North America were ravaged by the devastating skeletal consequences of rickets. Finding that exposure to ultraviolet radiation or sunlight treated and prevented rickets led to the ultraviolet irradiation of foods including milk. These practices along with the fortification of a variety of foods including dairy products with vitamin D and widespread use of cod liver oil eradicated rickets as a significant health problem by the late 1930s. Many countries mandated the fortification of milk with vitamin D to prevent rickets during wartime shortages. In the 1950s, in Europe, many countries forbid fortification of dairy and food products except breakfast cereals and margarine because of an outbreak of vitamin D intoxication in neonates. Vitamin D deficiency has again become a major public health interest with its association with osteoporosis, osteomalacia, fractures, and more recently with prevention of cancer, diabetes, heart disease and other chronic illnesses. Regular sun exposure has decreased due to changing lifestyles. Vitamin D deficiency is especially prevalent in dark skinned children and adults living in Northern latitudes, and obese children and adults. Improving the vitamin D status worldwide would have dramatic effects on public health, and reduce healthcare costs for many chronic diseases. The most cost-effective way to remedy this deficiency is to increase food fortification with higher levels of vitamin D along with sensible sun exposure, and adequate vitamin D supplementation. I review the pathophysiology of vitamin D deficiency and its health consequences and provide recommendations for a new policy approach to this vital public health issue.


Context: The Food and Drug Administration Modernization Act of 1997 (FDAMA) and the FDA Amendment Act of 2007 (FDAAA), respectively, established mandates for registration of interventional human research studies on the website clinicaltrials. gov (CTG) and for posting of results of completed studies. Objective: To characterise, contrast and explain rates of compliance with ontime registration of new studies and posting of results for completed studies on CTG. Design: Statistical analysis of publically available data downloaded from the CTG website. Participants: US studies registered on CTG since 1 November 1999, the date when the CTG website became operational, through 24 June 2011, the date the data set was downloaded for analysis. Main outcome measures: Ontime registration (within 21 days of study start); average delay from study start to registration; proportion of studies posting their results from within the group of studies listed as completed on CTG. Results: As of 24 June 2011, CTG contained 54 890 studies registered in the USA. Prior to 2005, an estimated 80% of US studies were not being registered. Among registered studies, only 55.7% registered within the 21-day reporting window. The average delay on CTG was 322 days. Between 28 September 2007 and June 23 2010, 28% of intervention studies at Phase II or beyond posted their study results on CTG, compared with 8.4% for studies without industry funding (RR 4.2, 95% CI 3.7 to 4.8). Factors associated with posting of results included exclusively paediatric studies (adjusted OR (AOR) 2.9, 95% CI 2.1 to 4.0), and later phase clinical trials (relative to Phase II studies, AOR for Phase III was 3.4, 95% CI 2.8 to 4.1; AOR for Phase IV was 6.0, 95% CI4.8 to 7.6). Conclusions: Non-compliance with FDAMA and FDAAA appears to be very common, although compliance is higher for studies sponsored by industry. Further oversight may be required to improve compliance.


Douglas S.D.,Childrens Hospital of Philadelphia | Leeman S.E.,Boston University
Annals of the New York Academy of Sciences | Year: 2011

The G protein-coupled receptor (GPCR), neurokinin-1 receptor (NK1R), and its preferred ligand, substance P (SP), are reviewed in relationship to the immune system and selected infections. NK1R and SP are ubiquitous throughout the animal kingdom. This important pathway has unique functions in numerous cells and tissues. The interaction of SP with its preferred receptor, NK1R, leads to the activation of nuclear factor-kappa B (NF-κB) and proinflammatory cytokines. NK1R has two isoforms, both a full-length and a truncated form. These isoforms have different functional significances and differ in cell signaling capability. The proinflammatory signals modulated by SP are important in bacterial, viral, fungal, and parasitic diseases, as well as in immune system function. The SP-NK1R system is a major class 1, rhodopsin-like GPCR ligand-receptor interaction. © 2010 New York Academy of Sciences.


Background: Childhood maltreatment has been linked to adolescent substance use in cross-sectional studies but the studies were unable to test the associations between childhood maltreatment and changes in substance use patterns during adolescence. The present study investigated the linkages between exposure to childhood maltreatment and developmental trends of alcohol, cannabis, cocaine, opioid, and hallucinogen use among high-risk adolescents. Methods: We used a sample of 937 adolescents (mean age: 15.9 years; range: 13-18), who were selected from five publicly-funded service systems, to examine the extent to which childhood maltreatment may influence changes in patterns of adolescent substance use over time. Results: The present study identified a 3-class model of adolescent substance use. Mover-stayer latent transition analyses (LTA) indicated that progression toward heavy polysubstance use increased with experience of childhood maltreatment. Findings also suggested that older male adolescents (ages 15-18) who are involved with public service systems are at high risk for developing and maintaining multiple-substance use in adolescence. Conclusions: Experience of childhood maltreatment is associated with problematic patterns of adolescent substance use and may shape the longitudinal course of substance use during adolescence. Copyright © American Academy of Addiction Psychiatry.


Olsson P.A.T.,Lund University | Park H.S.,Boston University
Acta Materialia | Year: 2011

In this work, we present results from atomistic simulations of gold nanowires under axial compression, with a focus on examining the effects of both axial and surface orientation effects on the buckling behavior. This was accomplished by using molecular statics simulations while considering three different crystallographic systems: 〈1 0 0〉/{1 0 0}, 〈1 0 0〉/{1 1 0} and 〈1 1 0〉/{1 1 0}{1 0 0}, with aspect ratios spanning from 20 to 50 and cross-sectional dimensions ranging from 2.45 to 5.91 nm. The simulations indicate that there is a deviation from the inverse square length dependence of critical forces predicted from traditional linear elastic Bernoulli-Euler and Timoshenko beam theories, where the nature of the deviation from the perfect inverse square length behavior differs for different crystallographic systems. This variation is found to be strongly correlated to either stiffening or increased compliance of the tangential stiffness due to the influence of nonlinear elasticity, which leads to normalized critical forces that decrease with decreasing aspect ratio for the 〈1 0 0〉/{1 0 0} and 〈1 0 0〉/{1 1 0} systems, but increase with decreasing aspect ratio for the 〈1 1 0〉/{1 1 0}{1 0 0} system. In contrast, it was found that the critical strains are all lower than their bulk counterparts, and that the critical strains decrease with decreasing cross-sectional dimensions; the lower strains may be an effect emanating from the presence of the surfaces, which are all more elastically compliant than the bulk and thus give rise to a more compliant flexural rigidity. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Rosenberg L.,Boston University
Cancer causes & control : CCC | Year: 2013

Active smoking and passive smoking have been associated with increased risk of breast cancer. The purpose of the present study was to prospectively assess associations of smoking with breast cancer and identify subgroups at higher risk among African-American women. Based on 1,377 incident cases identified during 14 years of follow-up in the Black Women's Health Study, we assessed active and passive smoking in relation to breast cancer incidence by menopausal status, estrogen receptor status, and other factors. Incidence rate ratios (IRR) and 95 % confidence intervals (CI) for categories of smoking relative to no active or passive smoking were calculated from Cox proportional hazards models, controlling for breast cancer risk factors. Active smoking was associated with increased risk of premenopausal breast cancer. The IRR was 1.21 (95 % CI 0.90-1.62) for premenopausal breast cancer overall and 1.70 (95 % CI 1.05-2.75) for premenopausal breast cancer associated with beginning smoking before age 18 together with accumulation of ≥20 pack years. The positive association with premenopausal breast cancer was most apparent for estrogen-receptor-positive cancer. Passive smoking was also associated with increased risk of premenopausal breast cancer (IRR = 1.42, 95 % CI 1.09-1.85), based on information on passive smoking at home and work. Neither active nor passive smoking was associated with increased risk of postmenopausal breast cancer. These results strengthen the evidence that both active and passive smoking increase the incidence of premenopausal breast cancer.


Jackiw R.,Massachusetts Institute of Technology | Pi S.-Y.,Boston University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We examine the local conformal invariance (Weyl invariance) in tensor-scalar theories used in recently proposed conformal cosmological models. We show that the Noether currents associated with Weyl invariance in these theories vanish. We assert that the corresponding Weyl symmetry does not have any dynamical role. © 2015 American Physical Society.


In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE with added CR (PE/CR). During treatment, bi-weekly self-report measures of posttraumatic and depressive symptoms were administered. Multilevel mediational analyses indicated that during PE, changes in posttraumatic symptoms accounted for 80.3% of changes in depressive symptoms, whereas changes in depressive symptoms accounted for 45.0% of changes in posttraumatic symptoms. During PE/CR, changes in posttraumatic symptoms accounted for 59.6% of changes in depressive symptoms, and changes in depressive symptoms accounted for 50.7% of changes in posttraumatic symptoms. This pattern of results suggests that PE primarily affects posttraumatic symptoms, which in turn affect depressive symptoms. In contrast, PE/CR results in a more reciprocal relationship between posttraumatic and depressive symptoms.


Lin J.-W.,Boston University
Journal of Neurophysiology | Year: 2013

At the crayfish opener neuromuscular junction, axons branch repeatedly before synapsing onto muscle fibers as varicosities. Excitability of these axons was examined with two-electrode current clamp before and after partial block of Na+ channels with 1 nM tetrodotoxin. 4-Aminopyridine (200;xM) was added to homogenize nonuniformity in K+ channel density. The impact of tetrodotoxin was evaluated in terms of action potential (AP) amplitude, rate of rise, and threshold. All three parameters were more severely affected at the secondary than the primary branching point (BP). Both BPs fired continuously during 1-s current steps before tetrodotoxin. After tetrodotoxin, the secondary BP fired only in brief bursts, whereas the primary BP still fired continuously. Despite this diminished excitability at the secondary BP, no failure in orthodromic AP conduction was observed. AP waveform at terminals (APf) was examined with voltage indicators. For orthodromic APs, reduction in AP amplitude and prolongation of AP rise time in tetrodotoxin were more pronounced in terminals than at the secondary BP. For APs initiated at the secondary BP, APf sometimes failed to show a spikelike waveform in tetrodotoxin. This degraded APf was not due to averaging variable AP invasion into terminals, because the variance of APf traces did not increase in tetrodotoxin. Tetrodotoxin applied in the absence of 4-aminopyridine showed an impact on the distal axon similar but less distinct than that recorded with 4-aminopyridine. In conclusion, the distal axon is more sensitive to tetrodotoxin than the proximal axon, such that AP waveform degrades as it propagates toward terminals in tetrodotoxin. © 2013 the American Physiological Society.


Ma N.,University of California at Berkeley | Ishwar P.,Boston University
IEEE Transactions on Information Theory | Year: 2011

Motivated by video coding applications, the problem of sequential coding of correlated sources with encoding and/or decoding frame-delays is studied. The fundamental tradeoffs between individual frame rates, individual frame distortions, and encoding/decoding frame-delays are derived in terms of a single-letter information-theoretic characterization of the rate-distortion region for general interframe source correlations and certain types of potentially frame specific and coupled single-letter fidelity criteria. The sum-rate-distortion region is characterized in terms of generalized directed information measures highlighting their role in delayed sequential source coding problems. For video sources which are spatially stationary memoryless and temporally Gauss-Markov, MSE frame distortions, and a sum-rate constraint, our results expose the optimality of idealized differential predictive coding among all causal sequential coders, when the encoder uses a positive rate to describe each frame. Somewhat surprisingly, causal sequential encoding with one-frame-delayed noncausal sequential decoding can exactly match the sum-rate-MSE performance of joint coding for all nontrivial MSE-tuples satisfying certain positive semidefiniteness conditions. Thus, even a single frame-delay holds potential for yielding significant performance improvements. Generalizations to higher order Markov sources are also presented and discussed. A rate-distortion performance equivalence between, causal sequential encoding with delayed noncausal sequential decoding, and delayed noncausal sequential encoding with causal sequential decoding, is also established. © 2011 IEEE.


Corkey B.E.,Boston University
Diabetes | Year: 2012

The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Dr. Barbara E. Corkey received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 71st Scientific Sessions, 24-28 June 2011, San Diego, California. She presented the Banting Lecture, "Hyperinsulinemia: Cause or Consequence?" on Sunday, 26 June 2011. © 2012 by the American Diabetes Association.


Debette S.,Lariboisiere Hospital | Debette S.,University of Paris Pantheon Sorbonne | Debette S.,Boston University
Current Opinion in Neurology | Year: 2014

PURPOSE OF REVIEW: Cervical artery dissection (CeAD) is a major cause of ischemic stroke in young and middle-aged adults, although relatively uncommon in the community. Recent large collaborative projects have provided new insights into mechanisms and risk factors of CeAD. RECENT FINDINGS: Pathologic changes observed at the media-adventitia border in temporal arteries of CeAD patients suggest a predisposing arterial wall weakness. In large multicenter series of CeAD patients, compared to age-matched healthy controls and patients with an ischemic stroke of another cause, hypertension and migraine, especially without aura, were confirmed as risk factors for CeAD, in addition to cervical trauma and recent infection. Hypercholesterolemia and being overweight were shown to be inversely associated with CeAD. Differences in risk factor profile and structural features between carotid and vertebral dissection suggest that their pathophysiology may partly differ. An association of CeAD with fibromuscular dysplasia and reversible cerebral vasoconstriction syndrome was described. Genetic risk factors of CeAD are still poorly understood. SUMMARY: Large cohorts of CeAD patients have refined our understanding of the pathophysiology and risk factors of CeAD, but the molecular mechanisms are still poorly understood. Ongoing high-throughput genetic projects will hopefully provide novel insight into the biological substrate of CeAD. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins.


Pearce E.N.,Boston University
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Thyroid hormone has multiple effectsonthe regulation of lipid synthesis, absorption,andmetabolism. Studies consistently demonstrate elevated levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, lipoprotein(a),andpossibly triglycerides in individuals with overt hypothyroidism, all of which are reversible with levothyroxine therapy. Although it is estimated that 1 to 11% of all patients with dyslipidemia have subclinical hypothyroidism, the effects of subclinical hypothyroidism on serum lipidvalues are less clear. Apolipoprotein B levels may be increased in patients with subclinical hypothyroidism. Although some studies have demonstrated that total cholesterol and LDL-C levels are elevated in patients with subclinical hypothyroidism, others have notshownany effect of subclinical hypothyroidism on these lipid measurements. Serum triglycerides, lipid subparticle size, and LDL-C oxidizability may be altered in subclinical hypothyroidism, but these studies have also been inconsistent. The preponderance of evidence suggests that HDL-C and lipoprotein(a) levels are not altered in subclinically hypothyroid patients. Smoking and insulin resistance may modify the effects of subclinical hypothyroidism on serum lipid values. Clinical trials to date have not consistently shown a beneficial effect of levothyroxine treatment on serum lipid levels in subclinically hypothyroid patients. Copyright © 2012 by The Endocrine Society.


Chae B.,Boston University
Insight (American Society of Ophthalmic Registered Nurses) | Year: 2013

Glaucoma is a common eye condition that affects millions of individuals worldwide, making it the second-leading cause of blindness. Because glaucoma is associated with increased IOP level, the primary goal in treatment of glaucoma includes lowering IOP to prevent further progression of the disease. While various surgical interventions exist, medical therapy is currently the first line of treatment. Medical treatment of glaucoma includes topical beta-blockers, alpha-2 agonists, prostaglandins, parasympathomimetics and CAIs. Anti-glaucoma agents help reduce IOP by affecting the production of aqueous humor or increasing the outflow of aqueous through the trabecular or uveoscleral pathway. Choosing an appropriate medical regimen can be challenging and various factors such as efficacy, safety, cost and patient compliance must be considered. First-line treatment is often topical beta-blockers or prostaglandin analogs. However, beta-blocking agents can be associated with systemic side effects and need to be used cautiously in patients with serious concomitant cardiopulmonary disease. Alpha-2 agonists and parasympathomimetics are often considered second- or third-line treatment options but good adjunctive agents. Oral CAIs are often indicated for patients with elevated IOP in an acute setting or for patients resistant to other glaucoma medications and patients who are not good surgical candidates.


The number of group members in an animal society can have a major influence on group members' life history, survival, and reproductive success. Identifying the factors that limit group size is therefore fundamental for a complete understanding of social behavior. Here, I examined the relationships between resource availability, social conflict, and group size in the coral-dwelling fish, Paragobiogon xanthosomus (Gobiidae). The size of the largest (breeding) female and the minimum size difference required for hierarchy stability strongly but not perfectly predicted maximum group size, suggesting that social conflicts and hierarchy structure set the upper limit on group size. Deviations in group size around the predicted maximum were explained by variation in average body size ratios but not by variation in coral size, suggesting that coral size does not directly influence group size. In contrast, coral size was a significant predictor of body size ratios, and possible explanations for this relationship are discussed. Group size may be limited by the social conflicts that characterize size-based dominance hierarchies. Ecological factors, namely coral size, may in turn play an indirect role via an effect on body size ratios. © 2011 Blackwell Verlag GmbH.


Sherman M.Y.,Boston University | Qian S.-B.,Cornell University
Trends in Biochemical Sciences | Year: 2013

Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins. A growing body of evidence suggests that the ribosome serves as a hub for co-translational folding, chaperone interaction, degradation, and stress response. Accordingly, in addition to the chaperone network and proteasome system, the ribosome has emerged as a major factor in protein homeostasis. Recent work revealed that high rates of elongation of translation negatively affect both the fidelity of translation and the co-translational folding of nascent polypeptides. Accordingly, by slowing down translation one can significantly improve protein folding. In this review, we discuss how to target translational processes to improve proteostasis and implications in treating protein misfolding diseases. © 2013 Elsevier Ltd.


Tannoury C.A.,Boston University | An H.S.,Rush University Medical Center
Spine Journal | Year: 2014

Background context Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a very potent osteogenic growth factor that has been used successfully in various spine fusions, obviating the need for autologous iliac crest bone graft harvest and therefore avoiding the associated morbidities. Purpose In the past few years, a tremendous increase in rhBMP-2 usage was noted, and concerns regarding costs, benefits, and safety issues were raised by many. The goal of this work was to provide a comprehensive review of the adverse events and complications associated with use of rhBMP-2. Study design Literature review. Methods This is a review of the current literature on the reported adverse events, complications, and concerns associated with rhBMP-2 use. Results This article discusses the wide spectrum of adverse outcomes related to rhBMP-2 use in the lumbar and the cervical spine; retrograde ejaculation, antibodies formation, postoperative radiculitis, postoperative nerve root injury, ectopic bone formation, vertebral osteolysis/edema, dysphagia and neck swelling, hematoma formation, interbody graft lucency, and wound healing complications are reviewed. Cost-related concerns, dosage considerations, carrier types, and theoretical carcinogenesis concerns were also presented. Conclusions Despite the excellent spinal fusion rates promoted by this powerful molecule, the increasingly reported adverse outcomes associated with bone morphogenetic protein usage have created real concerns. This article will provide the reader with a good understanding of the reported complications associated with rhBMP-2 use and ultimately help recognize its safety spectrum and limits for better clinical application. © 2014 Elsevier Inc. All rights reserved.


Many rural areas in the United States and throughout much of the postindustrial world are undergoing significant ecological, socioeconomic, and political transformations. The migration of urban and suburban dwellers into rural areas has led to the subdivision of large tracts of land into smaller parcels, which can complicate efforts to govern human-environmental problems. Non-point source (NPS) pollution from private rural lands is a particularly pressing human-environmental challenge that may be aggravated by changing land tenure. In this article, I report on a study of the governance and management of sediment (a common NPS pollutant) in the North Coastal basin of California, a region undergoing a transition from traditional extractive and agricultural land uses to rural residential and other alternative land uses. I focus on the differences in the governance and management across private timber, ranch, residential, vacation, and other lands in the region. I find that (1) the stringency and strength of sediment regulations differ by land use, (2) nonregulatory programs tend to target working landscapes, and (3) rural residential landowners have less knowledge of sediment control and report using fewer sediment-control techniques than landowners using their land for timber production or ranching. I conclude with an exploration of the consequences of these differences on an evolving rural landscape. © 2011 Springer Science+Business Media, LLC.


Denis G.V.,Boston University | Obin M.S.,Tufts University
Molecular Aspects of Medicine | Year: 2013

When humans eat more and exercise less, they tend to become obese and unhealthy. The molecular pathways that link obesity to serious diseases like Type 2 diabetes and cardiovascular disease have become a subject of intensive scientific investigation because the exploding prevalence of obesity worldwide represents a grave new threat to the health of hundreds of millions of people. However, obesity is not always destiny. Two important clinical populations have been valuable to understand the mechanisms behind this conundrum: individuals who exhibit metabolic dysfunction, diabetes and elevated cardiovascular disease risk despite a lean body type, and individuals who are relatively protected from these dangers despite significant obesity. Study of this second group of 'metabolically healthy obese' people in particular has been revealing because such individuals exhibit specific, identifiable, anatomic, cellular and molecular features that set them apart from the rest of us who suffer declining health with increasing weight. Here, we examine some of these features, including some mouse models that are informative of mechanism, and suggest hypotheses for further study, including the possibility that genes and pathways of the immune system might offer new diagnostic or therapeutic targets. © 2012 Elsevier Ltd. All rights reserved.


Marintchev A.,Boston University
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2013

The goal of this review is to summarize our current knowledge about the helicases involved in translation initiation and their roles in both general and mRNA-specific translation. The main topics covered are the mechanisms of helicase action, with emphasis on the roles of accessory domains and proteins; the functions performed by helicases in translation initiation; and the interplay between direct and indirect effects of helicases that also function in steps preceding translation initiation. Special attention is given to the dynamics of eIF4A binding and dissociation from eIF4F during mRNA unwinding. It is proposed that DHX29, as well as other helicases and translation initiation factors could also cycle on and off the translation initiation complexes, similar to eIF4A. The evidence in favor of this hypothesis and its possible implications for the mechanisms of translation initiation is discussed. This article is part of a Special Issue entitled: The biology of RNA helicases - Modulation for life. © 2013 Elsevier B.V.


Cahn Z.,University of California at Berkeley | Siegel M.,Boston University
Journal of Public Health Policy | Year: 2011

The issue of harm reduction has long been controversial in the public health practice of tobacco control. Health advocates have been reluctant to endorse a harm reduction approach out of fear that tobacco companies cannot be trusted to produce and market products that will reduce the risks associated with tobacco use. Recently, companies independent of the tobacco industry introduced electronic cigarettes, devices that deliver vaporized nicotine without combusting tobacco. We review the existing evidence on the safety and efficacy of electronic cigarettes. We then revisit the tobacco harm reduction debate, with a focus on these novel products. We conclude that electronic cigarettes show tremendous promise in the fight against tobacco-related morbidity and mortality. By dramatically expanding the potential for harm reduction strategies to achieve substantial health gains, they may fundamentally alter the tobacco harm reduction debate. © 2011 Macmillan Publishers Ltd.


Sherman M.,Boston University
Annals of the New York Academy of Sciences | Year: 2010

Various heat shock proteins, including Hsp72, are strongly upregulated in cancers, but their significance for tumor emergence and growth is poorly understood. Here we review recent data from several labs to indicate that Hsps, including Hsp72, are critical for growth of transformed but not normal cells. By manipulating expression and activity of Hsp72 and several oncogenes, it was shown that Hsp72 suppresses oncogene-induced senescence, thus allowing proliferation of cancer cells. Importantly, Hsp72 is able to suppress both p53-dependent and p53-independent senescence pathways. We propose that targeting Hsp72 may be a promising approach toward development of novel cancer therapies. © 2010 New York Academy of Sciences.


Zaia J.,Boston University
Methods in Molecular Biology | Year: 2013

The development of methods for capillary electrophoresis (CE) with on-line mass spectrometric detection (CE/MS) is driven by the need for accurate, robust, and sensitive glycomics analysis for basic biomedicine, biomarker discovery, and analysis of recombinant protein therapeutics. One important capability is to profile glycan mixtures with respect to the patterns of substituents including sialic acids, acetate, sulfate, phosphate, and other groups. There is additional need for an MS-compatible separation system capable of resolving carbohydrate isomers. This chapter summarizes applications of CS/MS to analysis of carbohydrates, glycoproteins, and glycopeptides that have appeared since 2008. Readers are referred to recent comprehensive reviews covering earlier publications. © Springer Science+Business Media, LLC 2013.


The yeast cell wall is a strong, but elastic, structure that is essential not only for the maintenance of cell shape and integrity, but also for progression through the cell cycle. During growth and morphogenesis, and in response to environmental challenges, the cell wall is remodeled in a highly regulated and polarized manner, a process that is principally under the control of the cell wall integrity (CWI) signaling pathway. This pathway transmits wall stress signals from the cell surface to the Rho1 GTPase, which mobilizes a physiologic response through a variety of effectors. Activation of CWI signaling regulates the production of various carbohydrate polymers of the cell wall, as well as their polarized delivery to the site of cell wall remodeling. This review article centers on CWI signaling in Saccharomyces cerevisiae through the cell cycle and in response to cell wall stress. The interface of this signaling pathway with other pathways that contribute to the maintenance of cell wall integrity is also discussed. © 2011 by the Genetics Society of America.


Lafyatis R.,Boston University
Nature Reviews Rheumatology | Year: 2014

Transforming growth factor β (TGF-β) has long been implicated in fibrotic diseases, including the multisystem fibrotic disease systemic sclerosis (SSc). Expression of TGF-β-regulated genes in fibrotic skin and lungs of patients with SSc correlates with disease activity, which points to this cytokine as the central mediator of pathogenesis. Patients with SSc often develop pulmonary arterial hypertension (PAH), a particularly lethal complication caused by vascular dysfunction. Several genetic diseases with vascular features related to SSc, such as familial PAH and hereditary haemorrhagic telangiectasia, are caused by mutations in the TGF-β-sensing ALK-1 signalling pathway. These observations suggest that increased TGF-β signalling causes both vascular and fibrotic features of SSc. The question of how latent TGF-β becomes activated in local SSc tissues is, therefore, central to the understanding of SSc. Both TGF-β1 and TGF-β3 can be activated by integrins αvβ6 and αvβ8, whose upregulation in bronchial epithelial cells can activate TGF-β in SSc lungs. Other αv integrins, thrombospondin-1 or altered TGF-β sequestration by matrix proteins might be important in other target tissues. How the immune system triggers this process remains unclear, although links between inflammation and TGF-β activation are emerging. Together, these observations provide an increasingly secure framework for understanding TGF-β in SSc pathogenesis. © 2014 Macmillan Publishers Limited. All rights reserved.


Steenkamp M.M.,New York University | Litz B.T.,Boston University | Hoge C.W.,U.S. Army | Marmar C.R.,New York University
JAMA - Journal of the American Medical Association | Year: 2015

IMPORTANCE: Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder common among military personnel and veterans. First-line psychotherapies most often recommended for PTSD consist mainly of "trauma-focused" psychotherapies that involve focusing on details of the trauma or associated cognitive and emotional effects. OBJECTIVE: To examine the effectiveness of psychotherapies for PTSD in military and veteran populations. EVIDENCE REVIEW: PubMed, PsycINFO, and PILOTS were searched for randomized clinical trials (RCTs) of individual and group psychotherapies for PTSD in military personnel and veterans, published from January 1980 to March 1, 2015.We also searched reference lists of articles, selected reviews, and meta-analyses. Of 891 publications initially identified, 36 were included. FINDINGS: Two trauma-focused therapies, cognitive processing therapy (CPT) and prolonged exposure, have been the most frequently studied psychotherapies for military-related PTSD. Five RCTs of CPT (that included 481 patients) and 4 RCTs of prolonged exposure (that included 402 patients) met inclusion criteria. Focusing on intent-to-treat outcomes, within-group posttreatment effect sizes for CPT and prolonged exposure were large (Cohen d range, 0.78-1.10). CPT and prolonged exposure also outperformed waitlist and treatment-as-usual control conditions. Forty-nine percent to 70%of participants receiving CPT and prolonged exposure attained clinically meaningful symptom improvement (defined as a 10- To 12-point decrease in interviewer-assessed or self-reported symptoms). However, mean posttreatment scores for CPT and prolonged exposure remained at or above clinical criteria for PTSD, and approximately two-thirds of patients receiving CPT or prolonged exposure retained their PTSD diagnosis after treatment (range, 60%-72%). CPT and prolonged exposure were marginally superior compared with non-trauma-focused psychotherapy comparison conditions. CONCLUSIONS AND RELEVANCE: In military and veteran populations, trials of the first-line trauma-focused interventions CPT and prolonged exposure have shown clinically meaningful improvements for many patients with PTSD. However, nonresponse rates have been high, many patients continue to have symptoms, and trauma-focused interventions show marginally superior results compared with active control conditions. There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non-trauma-focused. Copyright © 2015 American Medical Association.


Pencina M.J.,Boston University
American journal of epidemiology | Year: 2012

The discrimination of a risk prediction model measures that model's ability to distinguish between subjects with and without events. The area under the receiver operating characteristic curve (AUC) is a popular measure of discrimination. However, the AUC has recently been criticized for its insensitivity in model comparisons in which the baseline model has performed well. Thus, 2 other measures have been proposed to capture improvement in discrimination for nested models: the integrated discrimination improvement and the continuous net reclassification improvement. In the present study, the authors use mathematical relations and numerical simulations to quantify the improvement in discrimination offered by candidate markers of different strengths as measured by their effect sizes. They demonstrate that the increase in the AUC depends on the strength of the baseline model, which is true to a lesser degree for the integrated discrimination improvement. On the other hand, the continuous net reclassification improvement depends only on the effect size of the candidate variable and its correlation with other predictors. These measures are illustrated using the Framingham model for incident atrial fibrillation. The authors conclude that the increase in the AUC, integrated discrimination improvement, and net reclassification improvement offer complementary information and thus recommend reporting all 3 alongside measures characterizing the performance of the final model.


Mizgerd J.P.,Boston University
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Acute lower respiratory tract infection is responsible for an inordinate disease burden. Pulmonary immunity determines the outcomes of these infections. The innate and adaptive immune responses to microbes in the lung are critical to maintaining a healthy respiratory system and preventing pulmonary disease. In addition to balancing antimicrobial defense against the risk of lung injury during the immediate infection, the shaping of pulmonary immunity by respiratory infection contributes to the pathophysiology of many and even perhapsmost chronic pulmonary diseases. This Pulmonary Perspective aims to communicate two interconnected points. First, tremendous morbidity and mortality result from inadequate, misguided, or excessive pulmonary immunity. Second, our understanding of pulmonary immunity is at an exciting stage of rapid developments and discoveries, but many questions remain. Further advances in pulmonary immunity and elucidation of the cellular and molecular responses to microbes in the lung are needed to develop novel approaches to predicting, preventing, and curing respiratory disease. Copyright © 2012 by the American Thoracic Society.


Brainerd T.G.,Boston University
Astrophysical Journal | Year: 2010

The frequency and effects of multiple weak deflections in galaxy-galaxy lensing are investigated via Monte Carlo simulations. The lenses in the simulations are galaxies with known redshifts and known rest-frame blue luminosities. The frequency of multiple deflections above a given threshold shear value is quantified for discrete source redshifts, as well as for a set of sources that are broadly distributed in redshift space. In general, the closest lens in projection on the sky is not the only lens for a given source. In addition, 50% of the time the closest lens is not the most important lens for a given source. Compared to a naive single-deflection calculation in which only the lensing due to the closest weak lens is considered, a full multiple-deflection calculation yields a higher net shear for individual sources, as well as a higher mean tangential shear around the lens centers. The full multiple-deflection calculation also shows that galaxy-galaxy lensing may contribute a substantial amount to cosmic shear on small angular scales. The degree to which galaxy-galaxy lensing contributes to the small-scale cosmic shear is, however, quite sensitive to the mass adopted for the halos of L*B galaxies. Changing the halo mass by a factor of 2.5 changes the contribution of galaxy-galaxy lensing to the cosmic shear by a factor of 3 on scales of θ 1′. The contribution of galaxy-galaxy lensing to cosmic shear decreases rapidly with angular scale and extrapolates to zero at θ 5′. This last result is roughly independent of the halo mass and suggests that for scales θ ≳ 5′, cosmic shear is insensitive to the details of the gravitational potentials of large galaxies. © 2010 The American Astronomical Society. All rights reserved.


Best V.,Boston University
The Journal of the Acoustical Society of America | Year: 2012

This study tested the hypothesis that the reduction in spatial release from masking (SRM) resulting from sensorineural hearing loss in competing speech mixtures is influenced by the characteristics of the interfering speech. A frontal speech target was presented simultaneously with two intelligible or two time-reversed (unintelligible) speech maskers that were either colocated with the target or were symmetrically separated from the target in the horizontal plane. The difference in SRM between listeners with hearing impairment and listeners with normal hearing was substantially larger for the forward maskers (deficit of 5.8 dB) than for the reversed maskers (deficit of 1.6 dB). This was driven by the fact that all listeners, regardless of hearing abilities, performed similarly (and poorly) in the colocated condition with intelligible maskers. The same conditions were then tested in listeners with normal hearing using headphone stimuli that were degraded by noise vocoding. Reducing the number of available spectral channels systematically reduced the measured SRM, and again, more so for forward (reduction of 3.8 dB) than for reversed speech maskers (reduction of 1.8 dB). The results suggest that non-spatial factors can strongly influence both the magnitude of SRM and the apparent deficit in SRM for listeners with impaired hearing.


Bonegio R.,Boston University | Susztak K.,Yeshiva University
Experimental Cell Research | Year: 2012

Notch signaling is an evolutionarily conserved cell-cell signaling system that controls the fate of cells during development. In this review, we will summarize the literature that notch signaling during development controls nephron number and segmentation and therefore could influence kidney disease susceptibility. We will also review the evidence that Notch is reactivated in adult-onset diabetic kidney disease where it promotes the development of nephropathy including glomerulopathy, tubulointerstitial fibrosis and possibly arteriopathy and inflammation. Finally, we will review the evidence that blockade of pathogenic Notch signaling alters the natural history of diabetic nephropathy and thus could represent a novel therapeutic approach to the management of diabetic kidney disease. © 2012.


Polkovnikov A.,Boston University
Annals of Physics | Year: 2010

We discuss a phase space representation of quantum dynamics of systems with many degrees of freedom. This representation is based on a perturbative expansion in quantum fluctuations around one of the classical limits. We explicitly analyze expansions around three such limits: (i) corpuscular or Newtonian limit in the coordinate-momentum representation, (ii) wave or Gross-Pitaevskii limit for interacting bosons in the coherent state representation, and (iii) Bloch limit for the spin systems. We discuss both the semiclassical (truncated Wigner) approximation and further quantum corrections appearing in the form of either stochastic quantum jumps along the classical trajectories or the nonlinear response to such jumps. We also discuss how quantum jumps naturally emerge in the analysis of non-equal time correlation functions. This representation of quantum dynamics is closely related to the phase space methods based on the Wigner-Weyl quantization and to the Keldysh technique. We show how such concepts as the Wigner function, Weyl symbol, Moyal product, Bopp operators, and others automatically emerge from the Feynmann's path integral representation of the evolution in the Heisenberg representation. We illustrate the applicability of this expansion with various examples mostly in the context of cold atom systems including sine-Gordon model, one- and two-dimensional Bose-Hubbard model, Dicke model and others. © 2010 Elsevier Inc.


Chen J.-F.,Boston University | Eltzschig H.K.,Aurora University | Fredholm B.B.,Karolinska Institutet
Nature Reviews Drug Discovery | Year: 2013

Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors-either directly or indirectly-have now entered the clinic. However, only one adenosine receptor-specific agent-the adenosine A 2A receptor agonist regadenoson (Lexiscan; Astellas Pharma)-has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges.


Heyl M.,Ludwig Maximilians University of Munich | Heyl M.,TU Dresden | Polkovnikov A.,Boston University | Kehrein S.,University of Gottingen
Physical Review Letters | Year: 2013

A phase transition indicates a sudden change in the properties of a large system. For temperature-driven phase transitions this is related to nonanalytic behavior of the free energy density at the critical temperature: The knowledge of the free energy density in one phase is insufficient to predict the properties of the other phase. In this Letter we show that a close analogue of this behavior can occur in the real time evolution of quantum systems, namely nonanalytic behavior at a critical time. We denote such behavior a dynamical phase transition and explore its properties in the transverse-field Ising model. Specifically, we show that the equilibrium quantum phase transition and the dynamical phase transition in this model are intimately related. © 2013 American Physical Society.


Baum M.J.,Boston University
Frontiers in Neuroanatomy | Year: 2012

Until recently it was widely believed that the ability of female mammals (with the likely exception of women) to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female's vomeronasal organ (VNO) and their subsequent processing by a neural circuit that includes the accessory olfactory bulb (AOB), vomeronasal amygdala, and hypothalamus. Emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the main olfactory epithelium (MOE) of female mice which, in turn, leads to the activation of a population of glomeruli and abutting mitral cells in the main olfactory bulb (MOB). Anatomical results along with functional neuroanatomical data demonstrate that some of these MOB mitral cells project to the vomeronasal amygdala. These particular MOB mitral cells were selectively activated (i.e., expressed Fos protein) by exposure to male as opposed to female urinary volatiles. A similar selectivity to opposite sex urinary volatiles was also seen in mitral cells of the AOB of female mice. Behavioral data from female mouse, ferret, and human are reviewed that implicate the main olfactory system, in some cases interacting with the accessory olfactory system, in mate recognition. © 2012 Baum.


Meyer-Rath G.,Boston University | Meyer-Rath G.,University of Witwatersrand | Over M.,Center for Global Development
PLoS Medicine | Year: 2012

Policy discussions about the feasibility of massively scaling up antiretroviral therapy (ART) to reduce HIV transmission and incidence hinge on accurately projecting the cost of such scale-up in comparison to the benefits from reduced HIV incidence and mortality. We review the available literature on modelled estimates of the cost of providing ART to different populations around the world, and suggest alternative methods of characterising cost when modelling several decades into the future. In past economic analyses of ART provision, costs were often assumed to vary by disease stage and treatment regimen, but for treatment as prevention, in particular, most analyses assume a uniform cost per patient. This approach disregards variables that can affect unit cost, such as differences in factor prices (i.e., the prices of supplies and services) and the scale and scope of operations (i.e., the sizes and types of facilities providing ART). We discuss several of these variables, and then present a worked example of a flexible cost function used to determine the effect of scale on the cost of a proposed scale-up of treatment as prevention in South Africa. Adjusting previously estimated costs of universal testing and treatment in South Africa for diseconomies of small scale, i.e., more patients being treated in smaller facilities, adds 42% to the expected future cost of the intervention. © 2012 Meyer-Rath and Over.


Mueser K.T.,Boston University | Deavers F.,University of Central Florida | Penn D.L.,University of North Carolina at Chapel Hill | Cassisi J.E.,University of Central Florida
Annual Review of Clinical Psychology | Year: 2013

The current state of the literature regarding psychosocial treatments for schizophrenia is reviewed within the frameworks of the recovery model of mental health and the expanded stress-vulnerability model. Interventions targeting specific domains of functioning, age groups, stages of illness, and human service system gaps are classified as evidence-based practices or promising practices according to the extent to which their efficacy is currently supported by meta-analyses and individual randomized controlled trials (RCTs). Evidence-based practices include assertive community treatment (ACT), cognitive behavior therapy (CBT) for psychosis, cognitive remediation, family psychoeducation, illness self-management training, social skills training, and supported employment. Promising practices include cognitive adaptive therapy, CBT for posttraumatic stress disorder, first-episode psychosis intervention, healthy lifestyle interventions, integrated treatment for co-occurring disorders, interventions targeting older individuals, peer support services, physical disease management, prodromal stage intervention, social cognition training, supported education, and supported housing. Implications and future directions are discussed. Copyright © 2013 by Annual Reviews.


Morton L.M.,Boston University
Seminars in cutaneous medicine and surgery | Year: 2013

Cutaneous changes are a common feature of chronic venous insufficiency and include venous eczema and lipodermatosclerosis. This review will address the presumed pathophysiology of these conditions, their clinical findings, and important management strategies.


Fried I.,Boston University
International Journal for Numerical Methods in Engineering | Year: 2013

This paper presents high-order, single-point, iterative methods for the numerical solution of the general non-linear equilibrium equation. The methods are designed so that the approximations provided by the iterative process alternate about the targeted root, thus providing progressively better upper, as well as lower bounds on the sought root, which is thus numerically bracketed ever tighter. The effectiveness of the proposed methods is demonstrated by applying them to obtain close bounds on the extreme eigenvalues of the finite elements global stiffness matrix of the hanging string. © 2013 John Wiley & Sons, Ltd.


Gallagher K.P.,Boston University
Development Policy Review | Year: 2011

This article examines the extent to which measures to mitigate the current financial crisis and prevent future crises are permissible under a variety of bilateral, regional and multilateral trade and investment agreements. US trade and investment agreements, and, to a lesser extent, the World Trade Organization, leave little room to manoeuvre with capital controls, despite increasing evidence that certain controls can prevent or mitigate crises. Investment rules under the treaties of most capital-exporting nations allow for at least the use of temporary controls as a safeguard measure. The article offers a range of policies that could be deployed to improve US investment rules. © The Author 2011. Development Policy Review © 2011 Overseas Development Institute.


Mertz J.,Boston University
Nature Methods | Year: 2011

A key requirement for performing three-dimensional (3D) imaging using optical microscopes is that they be capable of optical sectioning by distinguishing in-focus signal from out-of-focus background. Common techniques for fluorescence optical sectioning are confocal laser scanning microscopy and two-photon microscopy. But there is increasing interest in alternative optical sectioning techniques, particularly for applications involving high speeds, large fields of view or long-term imaging. In this Review, I examine two such techniques, based on planar illumination or structured illumination. The goal is to describe the advantages and disadvantages of these techniques. © 2011 Nature America, Inc. All rights reserved.


Brody J.S.,Boston University
International Journal of Cancer | Year: 2012

Cigarette smoke alters the transcriptome of multiple tissues; those directly exposed to toxic products and those exposed to circulating components and metabolic products of tobacco smoke. In most tissues and organs that have been studied, the smoking transcriptome is characterized by increased expression of antioxidant and xenobiotic genes as well as a wide spectrum of inflammation-related genes, and potential oncogenic genes. Smoking is associated with an increased incidence of cancer in a number of organs both those directly exposed (lungs and airways) and those indirectly exposed (bladder, liver, pancreas). Individual transcriptomic responses vary, based to some degree on as yet to be clarified genetic factors, and likely how and what the individual has smoked. The complexity of individual responses to tobacco exposure and of smoking-related cancers in various organs is beginning to be revealed in transcriptomic and whole genome sequencing studies, of both tumors and cytologically normal appearing cells that have been exposed to cigarette smoke or its products creating a genomic "field of injury." The recent application of next generation sequencing to defining the transcriptome alterations induced by cigarette smoke holds the promise of discovering new approaches to personalized prevention and treatment of smoking-related lung diseases in the future. Copyright © 2012 UICC.


Hutyra L.R.,Boston University | Yoon B.,University of Washington | Alberti M.,University of Washington
Global Change Biology | Year: 2011

Most of our global population and its CO2 emissions can be attributed to urban areas. The process of urbanization changes terrestrial carbon stocks and fluxes, which, in turn, impact ecosystem functions and atmospheric CO2 concentrations. Using the Seattle, WA, region as a case study, this paper explores the relationships between aboveground carbon stocks and land cover within an urbanizing area. The major objectives were to estimate aboveground live and dead terrestrial carbon stocks across multiple land cover classes and quantify the relationships between urban cover and vegetation across a gradient of urbanization. We established 154 sample plots in the Seattle region to assess carbon stocks as a function of distance from the urban core and land cover [urban (heavy, medium, and low), mixed forest, and conifer forest land covers]. The mean (and 95% CI) aboveground live biomass for the region was 89±22MgCha-1 with an additional 11.8±4MgCha-1 of coarse woody debris biomass. The average live biomass stored within forested and urban land covers was 140±40 and 18±14MgCha-1, respectively, with a 57% mean vegetated canopy cover regionally. Both the total carbon stocks and mean vegetated canopy cover were surprisingly high, even within the heavily urbanized areas, well exceeding observations within other urbanizing areas and the average US forested carbon stocks. As urban land covers and populations continue to rapidly increase across the globe, these results highlight the importance of considering vegetation in urbanizing areas within the terrestrial carbon cycle. © 2010 Blackwell Publishing Ltd.


Lichtenstein D.R.,Boston University
Current Gastroenterology Reports | Year: 2011

Several hepatobiliary abnormalities have been described in association with inflammatory bowel disease (IBD), including primary sclerosing cholangitis (PSC), small duct PSC, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma, and cholelithiasis. PSC is the most common biliary condition in patients with IBD, with an incidence ranging from 2.5% to 7.5%. PSC usually progresses insidiously and eventually leads to cirrhosis independent of inflammatory bowel disease activity. There is a very high incidence of cholangiocarcinoma and an elevated risk for developing colon cancer in patients with PSC. Medical therapy has not proven successful in slowing disease progression or prolonging survival. Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins, such as cholestyramine or colestipol. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been conclusively demonstrated to improve survival or decrease the need for liver transplantation. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue. © Springer Science+Business Media, LLC 2011.


Stepp C.E.,Boston University
Journal of Speech, Language, and Hearing Research | Year: 2012

Purpose: Applying surface electromyography (sEMG) to the study of voice, speech, and swallowing is becoming increasingly popular. An improved understanding of sEMG and building a consensus as to appropriate methodology will improve future research and clinical applications.Method: An updated review of the theory behind recording sEMG for the speech and swallowing systems is provided. Several factors that are known to affect the content of the sEMG signal are discussed, and practical guidelines for sEMG recording and analysis are presented, focusing on special considerations within the context of the speech and swallowing anatomy. Results: Unique challenges are seen in application of sEMG to the speech and swallowing musculature owing to the small size of the muscles in relation to the sEMG detection volume and the present lack of knowledge about innervation zone locations. Conclusions: Despite the challenges discussed, application of sEMG to speech and swallowing has potential as a clinical and research tool when used correctly and is specifically suited to noninvasive clinical studies using between-condition or between-group comparisons for which detection of specific isolated muscle activities is not necessary. © American Speech-Language-Hearing Association.


Ravid K.,Boston University
Advances in Experimental Medicine and Biology | Year: 2010

Polyploidy, the state of having greater than a diploid content of DNA (e.g., tetraploid, octaploid, etc) has been recognized in a large variety of both, plant and animal cells. Human and murine megakaryocytes, hepatocytes, arterial smooth muscle cells and cardiac myocytes, all develop a certain degree of polyploidy during their normal lifespan. In addition, polyploid cells may be found in some tissues under conditions of stress, including uterine smooth muscle during pregnancy, aortic vascular smooth muscle cells during aging and hypertension, beta-cells in diabetic human or mouse thyroid cells in hyperthyroidism and cells in seminal vesicles with aging. Polyploid cells are also found in malignant tissues in which they are believed to contribute to the development of cells with intermediate DNA content values (e.g., 3n, 4.5n, etc.) (reviewed in refs. 1,2). With the use of micro-array, researchers have demonstrated that genetically identical yeast strains (Saccharomyces cerevisiae) with differences only in ploidy status (from haploid to tetraploid) display a substantial difference in gene expression, including of the G1 cyclins.3 This finding has suggested that DNA content per se might affect cellular functions. © 2010 Landes Bioscience and Springer Science+Business Media.


Carey K.,Boston University | Lin M.-Y.,Boston Medical Center
Health Affairs | Year: 2015

The Medicare Hospital Readmissions Reduction Program (HRRP), an initiative of the Affordable Care Act, imposes considerable financial penalties on hospitals with excess thirty-day readmissions for patients with selected high-volume conditions. We investigated the intended impact of the program by examining changes in thirty-day readmissions among Medicare patients admitted for three conditions targeted by the program in New York State, compared to Medicare patients with other conditions and with privately insured patients, before and after the program's introduction.We also examined potential unintended strategic responses by hospitals that might allow them to continue to treat target-condition patients while avoiding the readmission penalty.We found that thirty-day readmissions fell for the three conditions targeted by the HRRP, consistent with the goals of the program. Second, there also was a substantial fall in readmissions for a comparison group although not as large as for the target group, which suggests modest spillover effects in Medicare for other conditions. We did not find strong evidence of unintended effects associated with the program. These early findings suggest that the HRRP is affecting hospitals in the direction intended by the Affordable Care Act. © 2015 Project HOPE - The People-to-People Health Foundation, Inc.


Klitgord N.,Boston University
Genome informatics. International Conference on Genome Informatics | Year: 2010

Understanding the evolution and dynamics of metabolism in microbial ecosystems is an ongoing challenge in microbiology. A promising approach towards this goal is the extension of genome-scale flux balance models of metabolism to multiple interacting species. However, since the detailed distribution of metabolic functions among ecosystem members is often unknown, it is important to investigate how compartmentalization of metabolites and reactions affects flux balance predictions. Here, as a first step in this direction, we address the importance of compartmentalization in the well characterized metabolic model of the yeast Saccharomyces cerevisiae, which we treat as an "ecosystem of organelles". In addition to addressing the impact that the removal of compartmentalization has on model predictions, we show that by systematically constraining some individual fluxes in a de-compartmentalized version of the model we can significantly reduce the flux prediction errors induced by the removal of compartments. We expect that our analysis will help predict and understand metabolic functions in complex microbial communities. In addition, further study of yeast as an ecosystem of organelles might provide novel insight on the evolution of endosymbiosis and multicellularity.


The evolutionarily conserved aryl hydrocarbon receptor (AhR) has been studied for its role in environmental chemical-induced toxicity. However, recent studies have demonstrated that the AhR may regulate the hematopoietic and immune systems during development in a cell-specific manner. These results, together with the absence of an in vitro model system enabling production of large numbers of primary human hematopoietic progenitor cells (HPs) capable of differentiating into megakaryocyte- and erythroid-lineage cells, motivated us to determine if AhR modulation could facilitate both progenitor cell expansion and megakaryocyte and erythroid cell differentiation. Using a novel, pluripotent stem cell-based, chemically-defined, serum and feeder cell-free culture system, we show that the AhR is expressed in HPs and that, remarkably, AhR activation drives an unprecedented expansion of HPs, megakaryocyte-lineage cells, and erythroid-lineage cells. Further AhR modulation within rapidly expanding progenitor cell populations directs cell fate, with chronic AhR agonism permissive to erythroid differentiation and acute antagonism favoring megakaryocyte specification. These results highlight the development of a new Good Manufacturing Practice-compliant platform for generating virtually unlimited numbers of human HPs with which to scrutinize red blood cell and platelet development, including the assessment of the role of the AhR critical cell fate decisions during hematopoiesis.


Northrup N.A.,Boston University
Journal of Neuroimmune Pharmacology | Year: 2011

The focus of this commentary is to describe how neuroscience, immunology, and pharmacology intersect and how interdisciplinary research involving these areas has expanded knowledge in the area of neuroscience, in particular. Examples are presented to illustrate that the brain can react to the peripheral immune system and possesses immune function and that resident immune molecules play a role in normal brain physiology. In addition, evidence is presented that the brain immune system plays an important role in mediating neurodegenerative diseases, the aging process, and neurodevelopment and synaptic plasticity. The identification of these mechanisms has been facilitated by pharmacological studies and has opened new possibilities for pharmacotherapeutic approaches to the treatment of brain disorders. The emerging field of neuroimmune pharmacology exemplifies this interdisciplinary approach and has facilitated the study of basic cellular and molecular events and disease states and opens avenues for novel therapies. © 2010 Springer Science+Business Media, LLC.


Zhang Y.,Boston University | Jordan J.M.,University of North Carolina at Chapel Hill
Clinics in Geriatric Medicine | Year: 2010

Osteoarthritis (OA) is the most common joint disorder in the United States. Symptomatic knee OA occurs in 10% men and 13% in women aged 60 years or older. The number of people affected with symptomatic OA is likely to increase due to the aging of the population and the obesity epidemic. OA has a multifactorial etiology, and can be considered the product of an interplay between systemic and local factors. Old age, female gender, overweight and obesity, knee injury, repetitive use of joints, bone density, muscle weakness, and joint laxity all play roles in the development of joint OA, particularly in the weight-bearing joints. Modifying these factors may reduce the risk of OA and prevent subsequent pain and disability. © 2010 Elsevier Inc.


Heine W.F.,Boston University
Visual neuroscience | Year: 2011

The rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON-OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.


Bogan J.S.,Yale University | Kandror K.V.,Boston University
Current Opinion in Cell Biology | Year: 2010

Insulin regulates the trafficking of GLUT4 glucose transporters in fat and muscle cells. In unstimulated cells, GLUT4 is sequestered intracellularly in small, insulin-responsive vesicles. Insulin stimulates the translocation of these vesicles to the cell surface, inserting the transporters into the plasma membrane to enhance glucose uptake. Formation of the insulin-responsive vesicles requires multiple interactions among GLUT4, IRAP, LRP1, and sortilin, as well as recruitment of GGA and ACAP1 adaptors and clathrin. Once formed, the vesicles are retained within unstimulated cells by the action of TUG, Ubc9, and other proteins. In addition to acting at other steps in vesicle recycling, insulin releases this retention mechanism to promote the translocation and fusion of the vesicles at the cell surface. © 2010 Elsevier Ltd.


Zhang L.,Boston University
The Journal of biological chemistry | Year: 2012

Histone deacetylases (HDACs) play a critical role in the regulation of gene transcription, cardiac development, and diseases. The aim of this study was to test whether inhibition of HDACs induces myocardial repair and cardiac function restoration through c-kit signaling in mouse myocardial infarction models. Myocardial infarction in wild type Kit(+/+) and Kit(W)/Kit(W-v) mice was created following thoracotomy by applying permanent ligation to the left anterior descending artery. The HDAC inhibitor, trichostatin A (TSA, 0.1 mg/kg), was intraperitoneally injected daily for a consecutive 8 weeks after myocardial infarction. 5-Bromo-2-deoxyuridine (BrdU, 50 mg/kg) was intraperitoneally delivered every other day to pulse-chase label in vivo endogenous cardiac replication. Eight weeks later, inhibition of HDACs in vivo resulted in an improvement in ventricular functional recovery and the prevention of myocardial remodeling in Kit(+/+) mice, which was eliminated in Kit(W)/Kit(W-v) mice. HDAC inhibition promoted cardiac repairs and neovascularization in the infarcted myocardium, which were absent in Kit(W)/Kit(W-v) mice. Re-introduction of TSA-treated wild type c-kit(+) CSCs into Kit(W)/Kit(W-v) myocardial infarction heart restored myocardial functional improvement and cardiac repair. To further validate that HDAC inhibition stimulates c-kit(+) cardiac stem cells (CSCs) to facilitate myocardial repair, GFP(+) c-kit(+) CSCs were preconditioned with TSA (50 nmol/liter) for 24 h and re-introduced into infarcted hearts for 2 weeks. Preconditioning of c-kit(+) CSCs via HDAC inhibition with trichostatin A significantly increased c-kit(+) CSC-derived myocytes and microvessels and enhanced functional recovery in myocardial infarction hearts in vivo. Our results provide evidence that HDAC inhibition promotes myocardial repair and prevents cardiac remodeling, which is dependent upon c-kit signaling.


Straub J.E.,Boston University | Thirumalai D.,University of Maryland University College
Current Opinion in Structural Biology | Year: 2010

Identifying the principles that describe the formation of protein oligomers and fibrils with distinct morphologies is a daunting problem. Here we summarize general principles of oligomer formation gleaned from molecular dynamics simulations of A. β-peptides. The spectra of high free energy structures sampled by the monomer provide insights into the plausible fibril structures, providing a rationale for the 'strain phenomenon.' Heterogeneous growth dynamics of small oligomers of A. β16-22, whose lowest free energy structures are like nematic droplets, can be broadly described using a two-stage dock-lock mechanism. In the growth process, water is found to play various roles depending on the oligomer size, and peptide length, and sequence. Water may be an explicit element of fibril structure linked to various fibril morphologies. © 2010 Elsevier Ltd.


A hallmark of aging of the cardiac myocyte is impaired sarcoplasmic reticulum (SR) calcium uptake and relaxation due to decreased SR calcium ATPase (SERCA) activity. We tested the hypothesis that H2O2-mediated oxidation of SERCA contributes to impaired myocyte relaxation in aging. Young (5-month-old) and senescent (21-month-old) FVB wild-type (WT) or transgenic mice with myocyte-specific overexpression of catalase were studied. In senescent mice, myocyte-specific overexpression of catalase (1) prevented oxidative modification of SERCA as evidenced by sulfonation at Cys674, (2) preserved SERCA activity, (3) corrected impaired calcium handling and relaxation in isolated cardiac myocytes, and (4) prevented impaired left ventricular relaxation and diastolic dysfunction. Nitroxyl, which activates SERCA via S-glutathiolation at Cys674, failed to activate SERCA in freshly isolated ventricular myocytes from senescent mice. Finally, in adult rat ventricular myocytes in primary culture, adenoviral overexpression of SERCA in which Cys674 is mutated to serine partially preserved SERCA activity during exposure to H2O2. Oxidative modification of SERCA at Cys674 contributes to decreased SERCA activity and impaired myocyte relaxation in the senescent heart. Strategies to decrease oxidant levels and/or protect target proteins such as SERCA may be of value to preserve diastolic function in the aging heart.


Tanaka K.,Boston University
Journal of the American Heart Association | Year: 2013

Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and indicative of cardiac amyloid disease type. Fifty AL-CMP patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR patients). Clinical and laboratory evaluations including echocardiography were performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP), troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP-2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR, 1.041; P<0.01) were predictors for mortality for all patients with cardiac amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090; P<0.01). There were no prognostic factors for all-cause death in TTR-CMP patients. Circulating concentrations of MMPs and TIMPs may be useful in differentiating patients with AL-CMP from those with TTR-CMP, resulting in earlier diagnostic vigilance, and may add prognostic information. In addition to an elevated BNP level, female sex increased the risk of death in patients with cardiac amyloidoses.


Hylek E.,Boston University
Seminars in Thrombosis and Hemostasis | Year: 2013

Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder, and its prevalence is increasing worldwide. Atrial fibrillation confers a fivefold increased risk of stroke, and these strokes are associated with significant mortality and disability. The vitamin K antagonist, warfarin, has been the mainstay of anticoagulant therapy for patients with AF, reducing the risk of stroke by 65%. Despite its efficacy, warfarin remains underused in clinical practice because of its variable dose response, diet and medication interactions, and need for frequent monitoring. Stroke prevention in AF has entered an exciting therapeutic era with new classes of targeted anticoagulants that avoid the many pitfalls of the vitamin K antagonists. Dabigatran, an oral thrombin inhibitor, and the factor Xa inhibitors, rivaroxaban and apixaban, have demonstrated efficacy for stroke prevention and a reduced risk of intracranial hemorrhage relative to warfarin. Translating the efficacy of clinical trials into effective use of these novel agents in clinical practice will require an understanding of their pharmacokinetic profiles, dose selection, and management in select clinical situations. © 2013 by Thieme MedicalPublishers, Inc.


Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.


Heaney R.P.,Creighton University | Holick M.F.,Boston University
Journal of Bone and Mineral Research | Year: 2011

The IOM recommendations for vitamin D fail in a major way on logic, on science, and on effective public health guidance. Moreover, by failing to use a physiological referent, the IOM approach constitutes precisely the wrong model for development of nutritional policy. © 2011 American Society for Bone and Mineral Research. Copyright © 2011 American Society for Bone and Mineral Research.


Lee S.L.,Boston University
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2012

Purpose of review: Review of the management decisions that must be made by the endocrinologist during the use of radioactive iodine (RAI) therapy of hyperthyroidism and differentiated thyroid cancer. Recent findings: Since the 1940s radioactive I (RAI) therapy has been a major component of the treatment of hyperthyroidism and differentiated thyroid cancer. RAI is the most common definitive treatment of hyperthyroidism. Pretherapy decisions including use of antithyroid medication and low-iodine diet will be discussed with the relevant supportive literature. The method of semi-quantitative calculation used for RAI treatment of hyperthyroidism will be described. Evidence-based guideline for the management of differentiated thyroid cancer by the American Thyroid Association, new drug development and recent randomized controlled trials have changed current practice of how RAI is used for remnant ablation and adjuvant therapy of differentiated thyroid cancer. Summary: RAI is a common tool for the endocrinologist in the management of hyperthyroidism and differentiated thyroid cancer. Review of the management decisions and practice of RAI therapy will educate the endocrinologist of the literature supporting current RAI use in hyperthyroidism and new developments in limiting the radiation exposure to the patients with differentiated thyroid cancer. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Oates R.,Boston University
Asian Journal of Andrology | Year: 2012

When presented with an azoospermic patient, a thorough history and careful, considered physical examination often leads to a definite or presumptive diagnosis. An algorithmic, logical thought process is important to have in mind when embarking on the evaluation. Adjunctive laboratory tests, such as hormonal assays or genetic studies, are often complementary and/or additive and allow a very precise determination to be made as to the etiologies, either genetic or acquired. It is only with this information that a therapeutic plan can be made for the patient. As will be discussed, a targeted approach to testing is far more satisfying and cost-effective than a blind, shotgun approach. © 2012 AJA, SIMM &SJTU. All rights reserved.


Chaverri G.,Boston University
Behavioral Ecology and Sociobiology | Year: 2010

Even though social network analysis provides an important tool to characterize and compare societies, no studies have used its analytical applications to characterize patterns of sociality in bats. Here I use social network analysis to characterize and compare patterns of sociality between three populations of the leaf-roosting bat Thyroptera tricolor. Sites differed in the density of furled leaves used by T. tricolor for roosting. Finca had more leaves per hectare (77), followed by Ureña (58), and Esquinas (7). The time period over which the probability of association is halved based on fitted models was 1,086 days for Finca, 714 days for Ureña, and 303 days for Esquinas. Finca and Ureña had very similar network topologies, with several small clusters, high-clustering coefficients, short path lengths, low node betweenness, and high network robustness. Social networks at Esquinas were composed of one large cluster and several small isolated ones. Esquinas also had high-clustering coefficients, but path length and node betweenness were high. Network resilience was lower in Esquinas compared to Finca and Ureña. These results show that, unlike many other forest-dwelling bats that switch roosts regularly, T. tricolor does not exhibit a typical fission-fusion social system, and that resource availability seems to affect social networks in this bat. In addition, this study highlights the importance of emigrating individuals in maintaining social cohesion, establishing network connectedness, and determining network robustness. © 2010 Springer-Verlag.


Economo M.N.,Boston University | White J.A.,University of Utah
PLoS Computational Biology | Year: 2012

Computational studies as well as in vivo and in vitro results have shown that many cortical neurons fire in a highly irregular manner and at low average firing rates. These patterns seem to persist even when highly rhythmic signals are recorded