Northern California Institute for Research and Education

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Northern California Institute for Research and Education

San Francisco, CA, United States

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Yaffe K.,University of California at San Francisco | Yaffe K.,San Francisco Medical Center | Vittinghoff E.,University of California at San Francisco | Pletcher M.J.,University of California at San Francisco | And 4 more authors.
Circulation | Year: 2014

Background: Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife. Methods and results: In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol. Conclusions: Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation. © 2014 American Heart Association, Inc.

Liu H.,University of California at San Francisco | Liu H.,Northern California Institute for Research and Education | Matson G.B.,University of California at San Francisco
Magnetic Resonance in Medicine | Year: 2011

Although high-field MRI offers increased signal-to-noise, the nonuniform tipping produced by conventional radiofrequency (RF) pulses leads to spatially dependent contrast and suboptimal signal-to-noise, thus complicating the interpretation of the MR images. For structural imaging, three-dimensional sequences that do not make use of frequency-selective RF pulses have become popular. Therefore, the aim of this research was to develop non-slice-selective (NSS) RF pulses with immunity to both amplitude of (excitation) RF field (B 1) inhomogeneity and resonance offset. To accomplish this, an optimization routine based on optimal control theory was used to design new NSS pulses with desired ranges of immunity to B 1 inhomogeneity and resonance offset. The design allows the phase of transverse magnetization produced by the pulses to vary. Although the emphasis is on shallow tip designs, new designs for 30°, 60°, 90°, and 180° NSS RF pulses are also provided. These larger tip angle pulses are compared with recently published NSS pulses. Evidence is presented that the pulses presented in this article have equivalent performance but are shorter than the recently published pulses. Although the NSS pulses generate higher specific absorption rates and larger magnetization transfer effects than the rectangular pulses they replace, they nevertheless show promise for three-dimensional MRI experiments at high field. Copyright © 2011 Wiley Periodicals, Inc.

Chang T.T.,University of California at San Francisco | Hughes-Fulford M.,University of California at San Francisco | Hughes-Fulford M.,Northern California Institute for Research and Education
Biomaterials | Year: 2014

Three-dimensional (3D) culture of hepatocytes leads to improved and prolonged synthetic and metabolic functions, but the underlying molecular mechanisms are unknown. In order to investigate the role of 3D cell-cell interactions in maintaining hepatocyte differentiated functions exvivo, primary mouse hepatocytes were cultured either as monolayers on tissue culture dishes (TCD) or as 3D aggregates in rotating wall vessel (RWV) bioreactors. Global gene expression analyses revealed that genes upregulated in 3D culture were distinct from those upregulated during liver development and liver regeneration. Instead, they represented a diverse array of hepatocyte-specific functional genes with significant over-representation of hepatocyte nuclear factor 4α (Hnf4a) binding sites in their promoters. Expression of Hnf4a and many of its downstream target genes were significantly increased in RWV cultures as compared to TCD. Conversely, there was concomitant suppression of mesenchymal and cytoskeletal genes in RWV cultures that were induced in TCDs. These findings illustrate the importance of 3D cell-cell interactions in maintaining fundamental molecular pathways of hepatocyte function and serve as a basis for rational design of biomaterials that aim to optimize hepatocyte functions exvivo for biomedical applications. © 2013 Elsevier Ltd.

Nix L.M.,University of California at San Francisco | Nix L.M.,Northern California Institute for Research and Education | Tien P.C.,University of California at San Francisco
Current HIV/AIDS Reports | Year: 2014

HIV infection and its treatment have been associated with adipose tissue changes and disorders of glucose and lipid metabolism. The proportion of HIV-infected adults over the age of 50 is also growing placing HIV-infected adults at particular risk for metabolic perturbations and cardiovascular disease. The metabolic syndrome in HIV-infected adults has been increasingly studied but whether HIV is associated with greater risk remains unclear, likely because of the interplay of host, viral and antiretroviral factors that are associated with the components of the metabolic syndrome. The relationship between HIV and diabetes mellitus (DM) risk has also been debated. While the Framingham Risk Score is a well-accepted measure of 10-year cardiovascular risk in the general population, it may not accurately predict risk in the HIV setting due to HIV-related factors such as inflammation that are not accounted for. We summarize the recent literature on metabolic syndrome, DM, and cardiovascular risk in HIV-infected adults. © 2014 Springer Science+Business Media New York.

Frank J.A.,University of California at San Francisco | Frank J.A.,Northern California Institute for Research and Education
Annals of the New York Academy of Sciences | Year: 2012

The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair. © 2012 New York Academy of Sciences.

Yaffe K.,University of California at San Francisco | Falvey C.M.,University of California at San Francisco | Hoang T.,Northern California Institute for Research and Education
The Lancet Neurology | Year: 2014

Sleep disturbances and cognitive impairment are common in older adults. Mounting evidence points to a potential connection between sleep and cognitive function. Findings from observational studies support a role for sleep disturbances (particularly for sleep duration, sleep fragmentation, and sleep-disordered breathing) in the development of cognitive impairment. Less consistent evidence exists for associations of insomnia and circadian rhythm dysfunction with cognition. These findings suggest that the sleep-wake cycle plays a crucial part in brain ageing, pointing to a potential avenue for improvement of cognitive outcomes in people at risk of cognitive decline and dementia. Several biological mechanisms might underlie the association between sleep and cognition, but these pathways are not completely understood. Future studies that aim to clarify the association between sleep and cognition might help to identify people at risk of cognitive disorders and to facilitate the development of novel therapies to treat and potentially prevent both sleep disturbances and cognitive impairment. © 2014 Elsevier Ltd.

Uchida Y.,University of California at San Francisco | Uchida Y.,Dermatology Service and Research Unit | Uchida Y.,Northern California Institute for Research and Education
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2014

Ceramide, the backbone structure of all sphingolipids, as well as a minor component of cellular membranes, has a unique role in the skin, by forming the epidermal permeability barrier at the extracellular domains of the outermost layer of the skin, the stratum corneum, which is required for terrestrial mammalian survival. In contrast to the role of ceramide in forming the permeability barrier, the signaling roles of ceramide and its metabolites have not yet been recognized. Ceramide and/or its metabolites regulate proliferation, differentiation, and apoptosis in epidermal keratinocytes. Recent studies have further demonstrated that a ceramide metabolite, sphingosine-1-phosphate, modulates innate immune function. Ceramide has already been applied to therapeutic approaches for treatment of eczema associated with attenuated epidermal permeability barrier function. Pharmacological modulation of ceramide and its metabolites' signaling can also be applied to cutaneous disease prevention and therapy. The author here describes the signaling roles of ceramide and its metabolites in mammalian cells and tissues, including the epidermis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. © 2013 Elsevier B.V.

News Article | December 4, 2015

Young adults who watch a lot of TV and don't exercise much may start to see the effects of their unhealthy habits on their brains as early as midlife, a new study suggests. In the study, researchers looked at the TV viewing habits of more than 3,200 people, who were 25 years old, on average, at the start of the study. The people in the study who watched more than 3 hours of TV per day on average over the next 25 years were more likely to perform poorly on certain cognitive tests, compared with people who watched little TV, the researchers found. The results suggest that engaging in physical activity, as opposed to sitting and watching TV, is important for brain health, said study author Tina D. Hoang, of the Northern California Institute for Research and Education at the Veterans Affairs Medical Center in San Francisco. "Being physically active at any time in your life is good for your brain," Hoang said. In the study, the researchers asked the participants every five years how many hours per day they spent watching TV on average during the past year. At the start of the study, and again every two to five years later, the researchers asked the participants if, and how much, they exercised. [6 Foods That Are Good For Your Brain] After the 25 years, the researchers also examined the people's cognitive function using three tests that assessed the speed at which they processed information, their verbal memory and executive function — a number of mental skills that help people plan, organize and pay attention. The 353 people in the study who watched more than 3 hours of TV per day, on average, were more likely to perform worse on some of the tests, compared with people who watched little TV, the researchers found. And the 528 people in the study who exercised the least performed worse on one of the tests than the people who were more physically active, the researchers found. In addition, the 107 people in the study who both exercised the least and watched more than 3 hours of TV per day were twice as likely to perform poorly on the cognitive tests, compared with those who spent little time watching TV but exercised more. It is not clear exactly why spending more time watching TV may be linked to worse cognitive performance later in life. One hypothesis is that television viewing is not a cognitively engaging way of spending time, Hoang said. Or it could be that people who watch a lot of TV and don't exercise much may have other unhealthy lifestyle habits, such as a poor diet, which might also contribute to their worse cognitive function, she said. The new study was published today (Dec. 2) in the journal JAMA Psychiatry. Copyright 2015 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Kassebaum N.J.,University of Washington | Kassebaum N.J.,Seattle Childrens Hospital | Jasrasaria R.,Stanford University | Naghavi M.,University of Washington | And 11 more authors.
Blood | Year: 2014

Previous studies of anemia epidemiology have been geographically limited with little detail about severity or etiology. Using publicly available data, we estimated mild, moderate, and severe anemia from 1990 to 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data from the Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study. Global anemia prevalence in 2010 was 32.9%, causing 68.36 (95% uncertainty interval [UI], 40.98 to 107.54) million years lived with disability (8.8% of total for all conditions [95% UI, 6.3% to 11.7%]). Prevalence dropped for both sexes from 1990 to 2010, although more for males. Prevalence in females was higher in most regions and age groups. South Asia and Central, West, and East sub-Saharan Africa had the highest burden, while East, Southeast, and South Asia saw the greatest reductions. Iron-deficiency anemia was the top cause globally, although 10 different conditions were among the top 3 in regional rankings. Malaria, schistosomiasis, and chronic kidney disease-related anemia were the only conditions to increase in prevalence. Hemoglobinopathies made significant contributions in most populations. Burden was highest in children under age 5, the only age groups with negative trends from 1990 to 2010. (Blood. 2014;123(5):615-624).© 2014 by The American Society of Hematology.

Shi Y.,Northern California Institute for Research and Education | Meeker W.Q.,Iowa State University
IEEE Transactions on Reliability | Year: 2012

Accelerated Destructive Degradation Tests (ADDTs) provide timely product reliability information in practical applications. This paper describes Bayesian methods for ADDT planning under a class of nonlinear degradation models with one accelerating variable. We use a Bayesian criterion based on the estimation precision of a specified failure-time distribution quantile at use conditions to find optimum test plans. A large-sample approximation for the posterior distribution provides a useful simplification to the planning criterion. The general equivalence theorem (GET) is used to verify the global optimality of the numerically optimized test plans. Optimum plans usually provide insight for constructing compromise plans which tend to be more robust, and practically useful. We present a numerical example with a log-location-scale distribution to illustrate the Bayesian test planning methods, and to investigate the effects of the prior distribution and sample size on test planning results. © 2006 IEEE.

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