Showing papers by "Columbia University published in 2003"

Obesity is associated with macrophage accumulation in adipose tissue

Abstract: Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

Prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: conceptual issues and research evidence

Abstract: In this article the author reviews research evidence on the prevalence of mental disorders in lesbians, gay men, and bisexuals (LGBs) and shows, using meta-analyses, that LGBs have a higher prevalence of mental disorders than heterosexuals. The author offers a conceptual framework for understanding this excess in prevalence of disorder in terms of minority stress— explaining that stigma, prejudice, and discrimination create a hostile and stressful social environment that causes mental health problems. The model describes stress processes, including the experience of prejudice events, expectations of rejection, hiding and concealing, internalized homophobia, and ameliorative coping processes. This conceptual framework is the basis for the review of research evidence, suggestions for future research directions, and exploration of public policy implications. The study of mental health of lesbian, gay, and bisexual (LGB) populations has been complicated by the debate on the classification of homosexuality as a mental disorder during the 1960s and early 1970s. That debate posited a gay-affirmative perspective, which sought to declassify homosexuality, against a conservative perspective, which sought to retain the classification of homosexuality as a mental disorder (Bayer, 1981). Although the debate on classification ended in 1973 with the removal of homosexuality from the second edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric Association, 1973), its heritage has lasted. This heritage has tainted discussion on mental health of lesbians and gay men by associating— even equating— claims that LGB people have higher prevalences of mental disorders than heterosexual people with the historical antigay stance and the stigmatization of LGB persons (Bailey, 1999). However, a fresh look at the issues should make it clear that whether LGB populations have higher prevalences of mental disorders is unrelated to the classification of homosexuality as a mental disorder. A retrospective analysis would suggest that the attempt to find a scientific answer in that debate rested on flawed logic. The debated scientific question was, Is homosexuality a mental disorder? The operationalized research question that pervaded the debate was, Do homosexuals have high prevalences of mental disorders? But the research did not accurately operationalize the scientific question. The question of whether homosexuality should be considered a mental disorder is a question about classification. It can be answered by debating which behaviors, cognitions, or emotions should be considered indicators of a mental

The Patient Health Questionnaire-2: validity of a two-item depression screener.

Abstract: Background. A number of self-administered questionnaires are available for assessing depression severity, including the 9-item Patient Health Questionnaire depression module (PHQ-9). Because even briefer measures might be desirable for use in busy clinical settings or as part of comprehensive health

Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

Abstract: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

Network Structure and Knowledge Transfer: The Effects of Cohesion and Range:

Abstract: This research considers how different features of informal networks affect knowledge transfer. As a complement to previous research that has emphasized the dyadic tie strength component of informal...

Mapping cortical change across the human life span

Abstract: We used magnetic resonance imaging and cortical matching algorithms to map gray matter density (GMD) in 176 normal individuals ranging in age from 7 to 87 years. We found a significant, nonlinear decline in GMD with age, which was most rapid between 7 and about 60 years, over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces. Age effects were inverted in the left posterior temporal region, where GMD gain continued up to age 30 and then rapidly declined. The trajectory of maturational and aging effects varied considerably over the cortex. Visual, auditory and limbic cortices, which are known to myelinate early, showed a more linear pattern of aging than the frontal and parietal neocortices, which continue myelination into adulthood. Our findings also indicate that the posterior temporal cortices, primarily in the left hemisphere, which typically support language functions, have a more protracted course of maturation than any other cortical region.

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene

Abstract: Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.

Schema Therapy: A Practitioner's Guide

Abstract: Schema therapy: conceptual model -- Schema assessment and education -- Cognitive strategies -- Experiential strategies -- Behavioral pattern-breaking -- The therapy relationship -- Detailed schema treatment strategies -- Schema mode work -- Schema therapy for borderline personality disorder -- Schema therapy for narcissistic personality disorder.

The Metabolic Syndrome: Prevalence and Associated Risk Factor Findings in the US Population From the Third National Health and Nutrition Examination Survey, 1988-1994

Abstract: Coronary heart disease (CHD) is the leading cause of death in the United States.1 Factors associated with an increased risk of developing CHD that tend to cluster in individuals include older age, high blood pressure, a low level of high-density lipoprotein (HDL) cholesterol, a high triglyceride level, a high plasma glucose concentration, and obesity.2 These associated risk factors have been called syndrome X,3 the insulin resistance syndrome,4 or the metabolic syndrome.5 The mechanisms underlying the metabolic syndrome are not fully known; however, resistance to insulin-stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors.3,6,7 Insulin resistance is thought to be primarily due to obesity or an inherited genetic defect.8 As the prevalence of obesity increases in the United States, the prevalence of the metabolic syndrome may be expected to increase markedly. Estimates of the prevalence of the metabolic syndrome have varied substantially in part because of the variability of evaluated populations and of diagnostic criteria.9 The recent Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATP III) included clinical diagnosis guidelines for the metabolic syndrome.10 Compared with findings from earlier studies3-5 and World Health Organization guidelines, the new ATP III defines criteria readily measured in clinical practice. These consensus-generated guidelines provide the opportunity to assess the overall prevalence of the metabolic syndrome in the US population according to an accepted standard definition. In an initial study, Ford et al11 reported un-adjusted and age-adjusted metabolic syndrome prevalences of 21.8% and 23.7%, respectively, for the US population. The objectives of this study are to examine the prevalence of the metabolic syndrome by ethnicity, age, body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters), socioeconomic status, and lifestyle factors.

An efficient boosting algorithm for combining preferences

Abstract: We study the problem of learning to accurately rank a set of objects by combining a given collection of ranking or preference functions. This problem of combining preferences arises in several applications, such as that of combining the results of different search engines, or the "collaborative-filtering" problem of ranking movies for a user based on the movie rankings provided by other users. In this work, we begin by presenting a formal framework for this general problem. We then describe and analyze an efficient algorithm called RankBoost for combining preferences based on the boosting approach to machine learning. We give theoretical results describing the algorithm's behavior both on the training data, and on new test data not seen during training. We also describe an efficient implementation of the algorithm for a particular restricted but common case. We next discuss two experiments we carried out to assess the performance of RankBoost. In the first experiment, we used the algorithm to combine different web search strategies, each of which is a query expansion for a given domain. The second experiment is a collaborative-filtering task for making movie recommendations.

Neuroimaging studies of working memory: a meta-analysis.

Abstract: We performed meta-analyses on 60 neuroimaging (PET and fMRI) studies of working memory (WM), considering three types of storage material (spatial, verbal, and object), three types of executive function (continuous updating of WM, memory for temporal order, and manipulation of information in WM), and interactions between material and executive function. Analyses of material type showed the expected dorsal-ventral dissociation between spatial and nonspatial storage in the posterior cortex, but not in the frontal cortex. Some support was found for left frontal dominance in verbal WM, but only for tasks with low executive demand. Executive demand increased right lateralization in the frontal cortex for spatial WM. Tasks requiring executive processing generally produce more dorsal frontal activations than do storage-only tasks, but not all executive processes show this pattern. Brodmann's areas (BAs) 6, 8, and 9, in the superior frontal cortex, respond most when WM must be continuously updated and when memory for temporal order must be maintained. Right BAs 10 and 47, in the ventral frontal cortex, respond more frequently with demand for manipulation (including dual-task requirements or mental operations). BA 7, in the posterior parietal cortex, is involved in all types of executive function. Finally, we consider a potential fourth executive function: selective attention to features of a stimulus to be stored in WM, which leads to increased probability of activating the medial prefrontal cortex (BA 32) in storage tasks.

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study

Abstract: Background Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. Methods Serum antigliadin antibodies and anti–endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. Results In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. Conclusions Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know

Abstract: High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or γ-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is ≈10–50 mSv for an acute exposure and ≈50–100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others.

Second-order cone programming

Abstract: Second-order cone programming (SOCP) problems are convex optimization problems in which a linear function is minimized over the intersection of an affine linear manifold with the Cartesian product of second-order (Lorentz) cones. Linear programs, convex quadratic programs and quadratically constrained convex quadratic programs can all be formulated as SOCP problems, as can many other problems that do not fall into these three categories. These latter problems model applications from a broad range of fields from engineering, control and finance to robust optimization and combinatorial optimization. On the other hand semidefinite programming (SDP)—that is the optimization problem over the intersection of an affine set and the cone of positive semidefinite matrices—includes SOCP as a special case. Therefore, SOCP falls between linear (LP) and quadratic (QP) programming and SDP. Like LP, QP and SDP problems, SOCP problems can be solved in polynomial time by interior point methods. The computational effort per iteration required by these methods to solve SOCP problems is greater than that required to solve LP and QP problems but less than that required to solve SDP’s of similar size and structure. Because the set of feasible solutions for an SOCP problem is not polyhedral as it is for LP and QP problems, it is not readily apparent how to develop a simplex or simplex-like method for SOCP. While SOCP problems can be solved as SDP problems, doing so is not advisable both on numerical grounds and computational complexity concerns. For instance, many of the problems presented in the survey paper of Vandenberghe and Boyd [VB96] as examples of SDPs can in fact be formulated as SOCPs and should be solved as such. In §2, 3 below we give SOCP formulations for four of these examples: the convex quadratically constrained quadratic programming (QCQP) problem, problems involving fractional quadratic functions ∗RUTCOR, Rutgers University, e-mail:alizadeh@rutcor.rutgers.edu. Research supported in part by the U.S. National Science Foundation grant CCR-9901991 †IEOR, Columbia University, e-mail: gold@ieor.columbia.edu. Research supported in part by the Department of Energy grant DE-FG02-92ER25126, National Science Foundation grants DMS-94-14438, CDA-97-26385 and DMS-01-04282.

Do Defaults Save Lives

Abstract: The article discusses how should policy-makers choose defaults regarding organ donors. First, consider that every policy must have a no-action default, and defaults impose physical, cognitive, and, in the case of donation, emotional costs on those who must change their status. Second, note that defaults can lead to two kinds of misclassification, willing donors who are not identified or people who become donors against their wishes. Changes in defaults could increase donations in the United States of additional thousands of donors a year. Because each donor can be used for about three transplants, the consequences are substantial in lives saved.

Mitochondrial respiratory-chain diseases

Abstract: The mitochondrial respiratory chain has the crucial function of supplying the cell with energy in the form of ATP. Mutations affecting this chain can arise in mitochondrial or nuclear DNA and cause diseases known as mitochondrial encephalomyopathies. Because the rules of inheritance of mitochondrial and nuclear DNA differ considerably, these brain–muscle syndromes often have unpredictable clinical and genetic features.

The PredictProtein server

Abstract: PredictProtein (http://www.predictprotein.org) is an Internet service for sequence analysis and the prediction of protein structure and function. Users submit protein sequences or alignments; PredictProtein returns multiple sequence alignments, PROSITE sequence motifs, low-complexity regions (SEG), nuclear localization signals, regions lacking regular structure (NORS) and predictions of secondary structure, solvent accessibility, globular regions, transmembrane helices, coiled-coil regions, structural switch regions, disulfide-bonds, sub-cellular localization and functional annotations. Upon request fold recognition by prediction-based threading, CHOP domain assignments, predictions of transmembrane strands and inter-residue contacts are also available. For all services, users can submit their query either by electronic mail or interactively via the World Wide Web.

Do Defaults Save Lives

Abstract: Default options can lead to striking differences in preferences, with significant economic impact. The authors of this Policy Forum use natural and experimental data to examine the impact of simple policy defaults on the decision to become an organ donor, finding large effects that significantly increase donation rates.

Randomized, Double-Blind, Placebo-Controlled, Pilot Trial of Infliximab, a Chimeric Monoclonal Antibody to Tumor Necrosis Factor-α, in Patients With Moderate-to-Severe Heart Failure Results of the Anti-TNF Therapy Against Congestive Heart failure (ATTACH) Trial

Abstract: Background– Preclinical and preliminary clinical data have suggested that tumor necrosis factor-α (TNFα) may play a role in the evolution and progression of heart failure and that inhibition of TNFα may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFα, in patients with moderate-to-severe heart failure. Methods and Results– One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction ≤35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg ( P =0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominal P =0.043). Conclusions– Short-term TNFα antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.

Contrast restoration of weather degraded images

Abstract: Images of outdoor scenes captured in bad weather suffer from poor contrast. Under bad weather conditions, the light reaching a camera is severely scattered by the atmosphere. The resulting decay in contrast varies across the scene and is exponential in the depths of scene points. Therefore, traditional space invariant image processing techniques are not sufficient to remove weather effects from images. We present a physics-based model that describes the appearances of scenes in uniform bad weather conditions. Changes in intensities of scene points under different weather conditions provide simple constraints to detect depth discontinuities in the scene and also to compute scene structure. Then, a fast algorithm to restore scene contrast is presented. In contrast to previous techniques, our weather removal algorithm does not require any a priori scene structure, distributions of scene reflectances, or detailed knowledge about the particular weather condition. All the methods described in this paper are effective under a wide range of weather conditions including haze, mist, fog, and conditions arising due to other aerosols. Further, our methods can be applied to gray scale, RGB color, multispectral and even IR images. We also extend our techniques to restore contrast of scenes with moving objects, captured using a video camera.

Antimicrobial resistance: the example of Staphylococcus aureus

Abstract: In the early 1970s, physicians were finally forced to abandon their belief that, given the vast array of effective antimicrobial agents, virtually all bacterial infections were treatable. Their optimism was shaken by the emergence of resistance to multiple antibiotics among such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The evolution of increasingly antimicrobial-resistant bacterial species stems from a multitude of factors that includes the widespread and sometimes inappropriate use of antimicrobials, the extensive use of these agents as growth enhancers in animal feed, and, with the increase in regional and international travel, the relative ease with which antimicrobial-resistant bacteria cross geographic barriers (1–3). The irony of this trend toward progressively more resistant bacteria is that it coincides with a period of dramatically increased understanding of the molecular mechanisms of antimicrobial resistance. Unfortunately, while this insight has resulted in the identification of novel drug targets, it has not yet resulted in effective new chemotherapeutic agents. This paradox stands in sharp contrast to the dramatic progress made in antiviral (notably antiretroviral) therapy in the past ten years, where a number of newly discovered molecular targets have resulted in clinically effective therapeutic agents. Nowhere has this issue been of greater concern than with the Gram-positive bacteria pneumococci, enterococci, and staphylococci. Multidrug resistance is now the norm among these pathogens. S. aureus is perhaps the pathogen of greatest concern because of its intrinsic virulence, its ability to cause a diverse array of life-threatening infections, and its capacity to adapt to different environmental conditions (4, 5). The mortality of S. aureus bacteremia remains approximately 20–40% despite the availability of effective antimicrobials (6). S. aureus is now the leading overall cause of nosocomial infections and, as more patients are treated outside the hospital setting, is an increasing concern in the community (7, 8). S. aureus isolates from intensive care units across the country and from blood culture isolates worldwide are increasingly resistant to a greater number of antimicrobial agents (4, 8). Inevitably this has left fewer effective bactericidal antibiotics to treat these often life-threatening infections (Figure ​(Figure1).1). As rapidly as new antibiotics are introduced, staphylococci have developed efficient mechanisms to neutralize them (Table ​(Table11). Figure 1 S. aureus infections in intensive care units in the National Nosocomial Infections Surveillance System. Data include the total number of infections from 1987 to 1997. Isolates were tested for sensitivity to the following antimicrobial agents: gentamicin, ... Table 1 Mechanisms of S. aureus resistance to antimicrobialsA Recent reports of S. aureus isolates with intermediate or complete resistance to vancomycin portend a chemotherapeutic era in which effective bactericidal antibiotics against this organism may no longer be readily available (9, 10). This review will focus on the emergence of antimicrobial resistance in S. aureus. It will review the historical evolution of resistant strains, their spread, the molecular mechanisms of resistance for selected antibiotics, and progress toward the development of alternative drug targets or novel approaches for therapeutic or prophylactic intervention.

Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction

Abstract: Hepatic gluconeogenesis is absolutely required for survival during prolonged fasting or starvation, but is inappropriately activated in diabetes mellitus. Glucocorticoids and glucagon have strong gluconeogenic actions on the liver. In contrast, insulin suppresses hepatic gluconeogenesis. Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.

Abstract: Background Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. Methods We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Results Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 1...

Clarifying Achievement Goals and Their Impact.

Abstract: The study of achievement goals has illuminated basic motivational processes, though controversy surrounds their nature and impact. In 5 studies, including a longitudinal study in a difficult premed course, the authors show that the impact of learning and performance goals depends on how they are operationalized. Active learning goals predicted active coping, sustained motivation, and higher achievement in the face of challenge. Among performance goals, ability-linked goals predicted withdrawal and poorer performance in the face of challenge (but provided a “boost” to performance when students met with success); normative goals did not predict decrements in motivation or performance; and outcome goals (wanting a good grade) were in fact equally related to learning goals and ability goals. Ways in which the findings address discrepancies in the literature are discussed.

RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.

Abstract: Amyloid-β peptide (Aβ) interacts with the vasculature to influence Aβ levels in the brain and cerebral blood flow, providing a means of amplifying the Aβ-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Aβ infusion and studies in genetically manipulated mice show that Aβ interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Aβ across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Aβ-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Aβ in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Aβ-vascular interactions, including development of cerebral amyloidosis.

Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans

Abstract: Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.

Youth suicide risk and preventive interventions: A review of the past 10 years.

Abstract: Objective To review critically the past 10 years of research on youth suicide. Method Research literature on youth suicide was reviewed following a systematic search of PsycINFO and Medline. The search for school-based suicide prevention programs was expanded using two education databases: ERIC and Education Full Text. Finally, manual reviews of articles' reference lists identified additional studies. The review focuses on epidemiology, risk factors, prevention strategies, and treatment protocols. Results There has been a dramatic decrease in the youth suicide rate during the past decade. Although a number of factors have been posited for the decline, one of the more plausible ones appears to be the increase in antidepressants being prescribed for adolescents during this period. Youth psychiatric disorder, a family history of suicide and psychopathology, stressful life events, and access to firearms are key risk factors for youth suicide. Exciting new findings have emerged on the biology of suicide in adults, but, while encouraging, these are yet to be replicated in youths. Promising prevention strategies, including school-based skills training for students, screening for at-risk youths, education of primary care physicians, media education, and lethal-means restriction, need continuing evaluation studies. Dialectical behavior therapy, cognitive-behavioral therapy, and treatment with antidepressants have been identified as promising treatments but have not yet been tested in a randomized clinical trial of youth suicide. Conclusions While tremendous strides have been made in our understanding of who is at risk for suicide, it is incumbent upon future research efforts to focus on the development and evaluation of empirically based suicide prevention and treatment protocols.