Cambridge, MA, United States
Cambridge, MA, United States

Harvard University is a private Ivy League research university in Cambridge, Massachusetts, established in 1636. Its history, influence and wealth have made it one of the most prestigious universities in the world.Established originally by the Massachusetts legislature and soon thereafter named for John Harvard , Harvard is the United States' oldest institution of higher learning, and the Harvard Corporation is its first chartered corporation. Although never formally affiliated with any denomination, the early College primarily trained Congregation­alist and Unitarian clergy. Its curriculum and student body were gradually secularized during the 18th century, and by the 19th century Harvard had emerged as the central cultural establishment among Boston elites. Following the American Civil War, President Charles W. Eliot's long tenure transformed the college and affiliated professional schools into a modern research university; Harvard was a founding member of the Association of American Universities in 1900. James Bryant Conant led the university through the Great Depression and World War II and began to reform the curriculum and liberalize admissions after the war. The undergraduate college became coeducational after its 1977 merger with Radcliffe College.The University is organized into eleven separate academic units—ten faculties and the Radcliffe Institute for Advanced Study—with campuses throughout the Boston metropolitan area: its 209-acre main campus is centered on Harvard Yard in Cambridge, approximately 3 miles northwest of Boston; the business school and athletics facilities, including Harvard Stadium, are located across the Charles River in the Allston neighborhood of Boston and the medical, dental, and public health schools are in the Longwood Medical Area. Harvard has the largest financial endowment of any academic institution in the world, standing at $32.3 billion as of June 2013.Harvard is a large, highly residential research university. The nominal cost of attendance is high, but the University's large endowment allows it to offer generous financial aid packages. It operates several arts, cultural, and scientific museums, alongside the Harvard University Library which is the world's largest academic and private library system, comprising 79 individual libraries with over 18 million volumes.It has many eminent alumni. Eight U.S. presidents and several foreign heads of state have been graduates. It is also the alma mater of 62 living billionaires and 335 Rhodes Scholars, both the most in the country. To date, some 150 Nobel laureates have been affiliated as students, faculty, or staff. Wikipedia.

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Samocha K.E.,Harvard University
Nature Genetics | Year: 2014

Spontaneously arising (de novo) mutations have an important role in medical genetics. For diseases with extensive locus heterogeneity, such as autism spectrum disorders (ASDs), the signal from de novo mutations is distributed across many genes, making it difficult to distinguish disease-relevant mutations from background variation. Here we provide a statistical framework for the analysis of excesses in de novo mutation per gene and gene set by calibrating a model of de novo mutation. We applied this framework to de novo mutations collected from 1,078 ASD family trios, and, whereas we affirmed a significant role for loss-of-function mutations, we found no excess of de novo loss-of-function mutations in cases with IQ above 100, suggesting that the role of de novo mutations in ASDs might reside in fundamental neurodevelopmental processes. We also used our model to identify ∼1,000 genes that are significantly lacking in functional coding variation in non-ASD samples and are enriched for de novo loss-of-function mutations identified in ASD cases.

Willett W.,Harvard University
Nutritional Epidemiology | Year: 2013

This book is about the complex relationships between diet and risks of important diseases, such as cancer and cardiovascular disease. The book starts with an overview of research strategies in nutritional epidemiology - still a relatively new discipline that combines the vast knowledge compiled by nutritionists during this century with the methodologies developed by epidemiologists to study the determinants of diseases with multiple etiologies and long latent periods. A major section is devoted to the methods of dietary assessment using data on food intake, biochemical indicators of diet, and measures of body composition and size. The reproducibility and validity of each approach and the implications of measurement error are considered in detail. The analysis, presentation, and interpretation of data from epidemiologic studies of diet and disease are explored in depth. Particular attention is paid to the important influence of total energy intake on findings in such studies. To illustrate methodological issues in nutritional epidemiology, the relationships of dietary factors to the incidence of lung and breast cancer, heart disease, and birth defects are examined in depth. This new edition, in addition to updating existing chapters, includes new chapters on assessment of physical activity, nutrition, and genetic epidemic ology, and the role of nutritional epidemiology in policy. © 2013 by Oxford University Press. All rights reserved.

Wu H.,Harvard University
Cell | Year: 2013

Recent studies have revealed that multiple intracellular signaling proteins may assemble into structured, yet sometimes infinite, higher-order signaling machines for transmission of receptor activation information to cellular responses. These studies advance our understanding of cell signaling and implicate new molecular mechanisms in proximity-driven enzyme activation, threshold behavior, signal amplification, reduction of biological noise, and temporal and spatial control of signal transduction. © 2013 Elsevier Inc.

Mathis D.,Harvard University
Cell Metabolism | Year: 2013

Chronic, low-grade inflammation of visceral adipose tissue, and systemically, is a critical link between recent strikingly parallel rises in the incidence of obesity and type 2 diabetes. Macrophages have been recognized for some time to be critical participants in obesity-induced inflammation of adipose tissue. Of late, a score of other cell types of the innate and adaptive arms of the immune system have been suggested to play a positive or negative role in adipose tissue infiltrates. This piece reviews the existing data on these new participants; discusses experimental uncertainties, inconsistencies, and complexities; and puts forward a minimalist synthetic scheme. © 2013 Elsevier Inc.

Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. Interpretation Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits.

Pizzagalli D.A.,Harvard University
Annual Review of Clinical Psychology | Year: 2014

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (a) anhedonia, (b) dopamine, and (c) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affects mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reorcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. © 2014 by Annual Reviews.

Ridker P.M.,Harvard University
The Lancet | Year: 2014

Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60 000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications. © 2014 Elsevier Ltd.

Sachdev S.,Harvard University
Annual Review of Condensed Matter Physics | Year: 2012

I discuss the impact of gauge-gravity duality on our understanding of two classes of systems: conformal quantum matter and compressible quantum matter. The first conformal class includes systems, such as the boson Hubbard model in two spatial dimensions, which display quantum critical points described by conformal field theories. Questions associated with nonzero temperature dynamics and transport are difficult to answer using conventional field-theoretic methods. I argue that many of these can be addressed systematically using gauge-gravity duality and discuss the prospects for reliable computation of low-frequency correlations. Compressible quantum matter is characterized by the smooth dependence of the charge density, associated with a global U(1) symmetry, upon a chemical potential. Familiar examples are solids, superfluids, and Fermi liquids, but there are more exotic possibilities involving deconfined phases of gauge fields in the presence of Fermi surfaces. I survey the compressible systems studied using gauge-gravity duality and discuss their relationship to the condensed matter classification of such states. The gravity methods offer hope of a deeper understanding of exotic and strongly coupled compressible quantum states. Copyright © 2012 by Annual Reviews. All rights reserved.

Jain R.K.,Harvard University
Cancer Cell | Year: 2014

Ten antiangiogenic drugs targeting VEGF or its receptors are approved for cancer treatment. However, these agents, intended to block tumors' blood supply, may cause hypoxia, which may fuel tumor progression and treatment resistance. Emerging clinical data suggest that patients whose tumor perfusion or oxygenation increases in response to these agents may actually survive longer. Hence, strategies aimed at alleviating tumor hypoxia while improving perfusion may enhance the outcome of radiotherapy, chemotherapy, and immunotherapy. Here I summarize lessons learned from preclinical and clinical studies over the past decade and propose strategies for improving antiangiogenic therapy outcomes for malignant and nonmalignant diseases. © 2014 Elsevier Inc.

Libby P.,Harvard University
New England Journal of Medicine | Year: 2013

Our understanding of the pathogenesis of acute coronary syndromes has undergone a veritable revolution in the past 20 years. We now understand in molecular and cellular terms how most serious thrombotic complications of coronary atherosclerosis occur. In particular, inflammatory pathways have emerged as important drivers of plaque disruption and thrombosis. This insight into the pathophysiological features of acute coronary syndromes expands the scope of treatment of this disease beyond the traditional focus on reducing stenoses. The laboratory and clinical data summarized here should help us both to understand how contemporary therapies can reduce the risk of these events and to make further inroads against the residual burden of disease in the future. Copyright © 2013 Massachusetts Medical Society. All rights reserved.

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