Showing papers by "Stony Brook University published in 2010"

Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

Abstract: Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

Linking "big" personality traits to anxiety, depressive, and substance use disorders: a meta-analysis.

Abstract: We performed a quantitative review of associations between the higher order personality traits in the Big Three and Big Five models (i.e., neuroticism, extraversion, disinhibition, conscientiousness, agreeableness, and openness) and specific depressive, anxiety, and substance use disorders (SUD) in adults. This approach resulted in 66 meta-analyses. The review included 175 studies published from 1980 to 2007, which yielded 851 effect sizes. For a given analysis, the number of studies ranged from three to 63 (total sample size ranged from 1,076 to 75,229). All diagnostic groups were high on neuroticism (mean Cohen's d = 1.65) and low on conscientiousness (mean d = -1.01). Many disorders also showed low extraversion, with the largest effect sizes for dysthymic disorder (d = -1.47) and social phobia (d = -1.31). Disinhibition was linked to only a few conditions, including SUD (d = 0.72). Finally, agreeableness and openness were largely unrelated to the analyzed diagnoses. Two conditions showed particularly distinct profiles: SUD, which was less related to neuroticism but more elevated on disinhibition and disagreeableness, and specific phobia, which displayed weaker links to all traits. Moderator analyses indicated that epidemiologic samples produced smaller effects than patient samples and that Eysenck's inventories showed weaker associations than NEO scales. In sum, we found that common mental disorders are strongly linked to personality and have similar trait profiles. Neuroticism was the strongest correlate across the board, but several other traits showed substantial effects independent of neuroticism. Greater attention to these constructs can significantly benefit psychopathology research and clinical practice.

Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys

Abstract: Background Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. Aims To examine joint associations of 12 childhood adversities with first onset of 20 DSM–IV disorders in World Mental Health (WMH) Surveys in 21 countries. Method Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM–IV disorders with the WHO Composite International Diagnostic Interview (CIDI). Results Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. Conclusions Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis

Abstract: Context Cognitive impairment and functional disability are major determinants of caregiving needs and societal health care costs. Although the incidence of severe sepsis is high and increasing, the magnitude of patients' long-term cognitive and functional limitations after sepsis is unknown. Objective To determine the change in cognitive impairment and physical functioning among patients who survive severe sepsis, controlling for their presepsis functioning. Design, Setting, and Patients A prospective cohort involving 1194 patients with 1520 hospitalizations for severe sepsis drawn from the Health and Retirement Study, a nationally representative survey of US residents (1998-2006). A total of 9223 respondents had a baseline cognitive and functional assessment and had linked Medicare claims; 516 survived severe sepsis and 4517 survived a nonsepsis hospitalization to at least 1 follow-up survey and are included in the analysis. Main Outcome Measures Personal interviews were conducted with respondents or proxies using validated surveys to assess the presence of cognitive impairment and to determine the number of activities of daily living (ADLs) and instrumental ADLs (IADLs) for which patients needed assistance. Results Survivors' mean age at hospitalization was 76.9 years. The prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis, an odds ratio (OR) of 3.34 (95% confidence interval [CI], 1.53-7.25) in multivariable regression. Likewise, a high rate of new functional limitations was seen following sepsis: in those with no limits before sepsis, a mean 1.57 new limitations (95% CI, 0.99-2.15); and for those with mild to moderate limitations before sepsis, a mean of 1.50 new limitations (95% CI, 0.87-2.12). In contrast, nonsepsis general hospitalizations were associated with no change in moderate to severe cognitive impairment (OR, 1.15; 95% CI, 0.80-1.67; P for difference vs sepsis = .01) and with the development of fewer new limitations (mean among those with no limits before hospitalization, 0.48; 95% CI, 0.39-0.57; P for difference vs sepsis Conclusions Severe sepsis in this older population was independently associated with substantial and persistent new cognitive impairment and functional disability among survivors. The magnitude of these new deficits was large, likely resulting in a pivotal downturn in patients' ability to live independently.

Niche conservatism as an emerging principle in ecology and conservation biology.

Abstract: The diversity of life is ultimately generated by evolution, and much attention has focused on the rapid evolution of ecological traits. Yet, the tendency for many ecological traits to instead remain similar over time [niche conservatism (NC)] has many consequences for the fundamental patterns and processes studied in ecology and conservation biology. Here, we describe the mounting evidence for the importance of NC to major topics in ecology (e.g. species richness, ecosystem function) and conservation (e.g. climate change, invasive species). We also review other areas where it may be important but has generally been overlooked, in both ecology (e.g. food webs, disease ecology, mutualistic interactions) and conservation (e.g. habitat modification). We summarize methods for testing for NC, and suggest that a commonly used and advocated method (involving a test for phylogenetic signal) is potentially problematic, and describe alternative approaches. We suggest that considering NC: (1) focuses attention on the within-species processes that cause traits to be conserved over time, (2) emphasizes connections between questions and research areas that are not obviously related (e.g. invasives, global warming, tropical richness), and (3) suggests new areas for research (e.g. why are some clades largely nocturnal? why do related species share diseases?).

The Impact of Conservation on the Status of the World’s Vertebrates

Abstract: Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world's vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species.

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

Abstract: Objective The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes.

How Big is a Big Odds Ratio? Interpreting the Magnitudes of Odds Ratios in Epidemiological Studies

Abstract: The odds ratio (OR) is probably the most widely used index of effect size in epidemiological studies. The difficulty of interpreting the OR has troubled many clinical researchers and epidemiologists for a long time. We propose a new method for interpreting the size of the OR by relating it to differences in a normal standard deviate. Our calculations indicate that OR = 1.68, 3.47, and 6.71 are equivalent to Cohen's d = 0.2 (small), 0.5 (medium), and 0.8 (large), respectively, when disease rate is 1% in the nonexposed group; Cohen's d 0.8 when OR > 5.

Solar influences on climate

Abstract: The development of this review article has evolved from work carried out by an international team of the International Space Science Institute (ISSI), Bern, Switzerland, and from work carried out under the auspices of Scientific Committee on Solar Terrestrial Physics (SCOSTEP) Climate and Weather of the Sun‐Earth System (CAWSES‐1). The support of ISSI in providing workshop and meeting facilities is acknowledged, especially support from Y. Calisesi and V. Manno. SCOSTEP is acknowledged for kindly providing financial assistance to allow the paper to be published under an open access policy. L.J.G. was supported by the UK Natural Environment Research Council (NERC) through their National Centre for Atmospheric Research (NCAS) Climate program. K.M. was supported by a Marie Curie International Outgoing Fellowship within the 6th European Community Framework Programme. J.L. acknowledges support by the EU/FP7 program Assessing Climate Impacts on the Quantity and Quality of Water (ACQWA, 212250) and from the DFG Project Precipitation in the Past Millennium in Europe (PRIME) within the Priority Program INTERDYNAMIK. L.H. acknowledges support from the U.S. NASA Living With a Star program. G.M. acknowledges support from the Office of Science (BER), U.S. Department of Energy, Cooperative Agreement DE‐FC02‐97ER62402, and the National Science Foundation. We also wish to thank Karin Labitzke and Markus Kunze for supplying an updated Figure 13, Andrew Heaps for technical support, and Paul Dickinson for editorial support. Part of the research was carried out under the SPP CAWSES funded by GFG. J.B. was financially supported by NCCR Climate–Swiss Climate Research.

Event-Related Potentials, Emotion, and Emotion Regulation: An Integrative Review

Abstract: Progress in the study of emotion and emotion regulation has increasingly been informed by neuroscientific methods. This article focuses on two components of the event-related potential (ERP)--the P300 and the late positive potential (LPP)--and how they can be used to understand the interaction between the more automatic and controlled processing of emotional stimuli. Research is reviewed exploring: the dynamics of emotional response as indexed at early and late latencies; neurobiological correlates of emotional response; individual and developmental differences; ways in which the LPP can be utilized as a measure of emotion regulation. Future directions for the application of ERP/electroencephalogram (EEG) in achieving a more complete understanding of emotional processing and its regulation are presented.

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project

Abstract: We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

Adaptive Evolution of Pelvic Reduction in Sticklebacks by Recurrent Deletion of a Pitx1 Enhancer

Abstract: The molecular mechanisms underlying major phenotypic changes that have evolved repeatedly in nature are generally unknown. Pelvic loss in different natural populations of threespine stickleback fish has occurred through regulatory mutations deleting a tissue-specific enhancer of the Pituitary homeobox transcription factor 1 (Pitx1) gene. The high prevalence of deletion mutations at Pitx1 may be influenced by inherent structural features of the locus. Although Pitx1 null mutations are lethal in laboratory animals, Pitx1 regulatory mutations show molecular signatures of positive selection in pelvic-reduced populations. These studies illustrate how major expression and morphological changes can arise from single mutational leaps in natural populations, producing new adaptive alleles via recurrent regulatory alterations in a key developmental control gene.

Structural conversion of neurotoxic amyloid-[beta]1-42 oligomers to fibrils

Abstract: The amyloid-beta(1-42) (Abeta42) peptide rapidly aggregates to form oligomers, protofibils and fibrils en route to the deposition of amyloid plaques associated with Alzheimer's disease. We show that low-temperature and low-salt conditions can stabilize disc-shaped oligomers (pentamers) that are substantially more toxic to mouse cortical neurons than protofibrils and fibrils. We find that these neurotoxic oligomers do not have the beta-sheet structure characteristic of fibrils. Rather, the oligomers are composed of loosely aggregated strands whose C termini are protected from solvent exchange and which have a turn conformation, placing Phe19 in contact with Leu34. On the basis of NMR spectroscopy, we show that the structural conversion of Abeta42 oligomers to fibrils involves the association of these loosely aggregated strands into beta-sheets whose individual beta-strands polymerize in a parallel, in-register orientation and are staggered at an intermonomer contact between Gln15 and Gly37.

A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity

Abstract: Dicer is a central enzyme in microRNA (miRNA) processing. We identified a Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory to dicer loss of function but were reduced in MZago2 (maternal-zygotic) mutants. We found that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutants showed delayed erythropoiesis that could be rescued by wild-type Ago2 or miR-451-duplex but not by catalytically dead Ago2. Changing the secondary structure of Dicer-dependent miRNAs to mimic that of pre-miR-451 restored miRNA function and rescued developmental defects in MZdicer mutants, indicating that the pre-miRNA secondary structure determines the processing pathway in vivo. We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer.

The equation of state from observed masses and radii of neutron stars

Abstract: We determine an empirical dense matter equation of state (EOS) from a heterogeneous data set of six neutron stars: three Type-I X-ray bursters with photospheric radius expansion, studied by ?zel et?al., and three transient low-mass X-ray binaries. We critically assess the mass and radius determinations from the X-ray burst sources and show explicitly how systematic uncertainties, such as the photospheric radius at touchdown, affect the most probable masses and radii. We introduce a parameterized EOS and use a Markov chain Monte Carlo algorithm within a Bayesian framework to determine nuclear parameters such as the incompressibility and the density dependence of the bulk symmetry energy. Using this framework we show, for the first time, that these parameters, predicted solely on the basis of astrophysical observations, all lie in ranges expected from nuclear systematics and laboratory experiments. We find significant constraints on the mass-radius relation for neutron stars, and hence on the pressure-density relation of dense matter. The predicted symmetry energy and the EOS near the saturation density are soft, resulting in relatively small neutron star radii around 11-12?km for M = 1.4 M ?. The predicted EOS stiffens at higher densities, however, and our preferred model for X-ray bursts suggests that the neutron star maximum mass is relatively large, 1.9-2.2 M ?. Our results imply that several commonly used equations of state are inconsistent with observations.

The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms Trial

Abstract: BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (>4 mm), had unfavorable dome/neck ratios ( RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42–76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.

In situ NMR observation of the formation of metallic lithium microstructures in lithium batteries

Abstract: Lithium metal has the highest volumetric and gravimetric energy density of all negative-electrode materials when used as an electrode material in a lithium rechargeable battery. However, the formation of lithium dendrites and/or ‘moss’ on the metal electrode surface can lead to short circuits following several electrochemical charge–discharge cycles, particularly at high rates, rendering this class of batteries potentially unsafe and unusable owing to the risk of fire and explosion. Many recent investigations have focused on the development of methods to prevent moss/dendrite formation. In parallel, it is important to quantify Li-moss formation, to identify the conditions under which it forms. Although optical and electron microscopy can visually monitor the morphology of the lithium-electrode surface and hence the moss formation, such methods are not well suited for quantitative studies. Here we report the use of in situ NMR spectroscopy, to provide time-resolved, quantitative information about the nature of the metallic lithium deposited on lithium-metal electrodes. The formation of lithium dendrites on the metal electrode surface of lithium batteries can lead to short circuits, making them potentially unsafe and unusable. The use of in situ NMR spectroscopy provides time-resolved and quantitative information about the nature of metallic lithium deposited on lithium-metal electrodes.

Observation of a centrality-dependent dijet asymmetry in lead-lead collisions at √sNN=2.76 Tev with the ATLAS detector at the LHC

Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

A human functional protein interaction network and its application to cancer data analysis

Abstract: One challenge facing biologists is to tease out useful information from massive data sets for further analysis. A pathway-based analysis may shed light by projecting candidate genes onto protein functional relationship networks. We are building such a pathway-based analysis system. We have constructed a protein functional interaction network by extending curated pathways with non-curated sources of information, including protein-protein interactions, gene coexpression, protein domain interaction, Gene Ontology (GO) annotations and text-mined protein interactions, which cover close to 50% of the human proteome. By applying this network to two glioblastoma multiforme (GBM) data sets and projecting cancer candidate genes onto the network, we found that the majority of GBM candidate genes form a cluster and are closer than expected by chance, and the majority of GBM samples have sequence-altered genes in two network modules, one mainly comprising genes whose products are localized in the cytoplasm and plasma membrane, and another comprising gene products in the nucleus. Both modules are highly enriched in known oncogenes, tumor suppressors and genes involved in signal transduction. Similar network patterns were also found in breast, colorectal and pancreatic cancers. We have built a highly reliable functional interaction network upon expert-curated pathways and applied this network to the analysis of two genome-wide GBM and several other cancer data sets. The network patterns revealed from our results suggest common mechanisms in the cancer biology. Our system should provide a foundation for a network or pathway-based analysis platform for cancer and other diseases.

Focused Cardiac Ultrasound in the Emergent Setting: A Consensus Statement of the American Society of Echocardiography and American College of Emergency Physicians

Abstract: The use of ultrasound has developed over the last 50 years into an indispensable first-line test for the cardiac evaluation of symptomatic patients. The technologic miniaturization and improvement in transducer technology, as well as the implementation of educational curriculum changes in residency training programs and specialty practice, have facilitated the integration of focused cardiac ultrasound into practice by specialties such as emergency medicine. In the emergency department, focused cardiac ultrasound has become a fundamental tool to expedite the diagnostic evaluation of the patient at the bedside and to initiate emergent treatment and triage decisions by the emergency physician.

A snapshot of the age distribution of psychological well-being in the United States

Abstract: Psychological well-being (WB) includes a person's overall appraisal of his or her life (Global WB) and affective state (Hedonic WB), and it is considered a key aspect of the health of individuals and groups. Several cross-sectional studies have documented a relation between Global WB and age. Little is known, however, about the age distribution of Hedonic WB. It may yield a different view of aging because it is less influenced by the cognitive reconstruction inherent in Global WB measures and because it includes both positive and negative components of WB. In this study we report on both Global and Hedonic WB assessed in a 2008 telephone survey of 340,847 people in the United States. Consistent with prior studies, Global WB and positive Hedonic WB generally had U-shaped age profiles showing increased WB after the age of 50 years. However, negative Hedonic WB variables showed distinctly different and stronger patterns: Stress and Anger steeply declined from the early 20s, Worry was elevated through middle age and then declined, and Sadness was essentially flat. Unlike a prior study, men and women had very similar age profiles of WB. Several measures that could plausibly covary with the age-WB association (e.g., having children at home) did not alter the age-WB patterns. Global and Hedonic WB measures appear to index different aspects of WB over the lifespan, and the postmidlife increase in WB, especially in Hedonic WB, deserves continued exploration.

Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women

Abstract: Context In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. Objective To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. Design, Setting, and Participants A total of 16 608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12 788 (83%) of the surviving participants. Main Outcome Measures Invasive breast cancer incidence and breast cancer mortality. Results In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. Conclusions Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. Trial Registration clinicaltrials.gov Identifier: NCT00000611

Automatic attribute discovery and characterization from noisy web data

Abstract: It is common to use domain specific terminology - attributes - to describe the visual appearance of objects. In order to scale the use of these describable visual attributes to a large number of categories, especially those not well studied by psychologists or linguists, it will be necessary to find alternative techniques for identifying attribute vocabularies and for learning to recognize attributes without hand labeled training data. We demonstrate that it is possible to accomplish both these tasks automatically by mining text and image data sampled from the Internet. The proposed approach also characterizes attributes according to their visual representation: global or local, and type: color, texture, or shape. This work focuses on discovering attributes and their visual appearance, and is as agnostic as possible about the textual description.

Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R)

Abstract: Community surveys consistently find that elderly people have much less clinical depression than younger people (Blazer & Hybels, 2005; Jorm, 2000). A number of explanations have been proposed for this finding, most focusing on the possibility that depression is underestimated among the elderly. Suggested biases include age-related differentials in recall, mortality, selection out of the household population into nursing homes, willingness to participate in surveys, and willingness to admit psychiatric symptoms in interviews (Schoevers et al., 2008; Snowdon, 1997). However, evidence for these methodological interpretations is weak (Ernst & Angst, 1995), leading some commentators to conclude that the low estimated prevalence of depression among the elderly is genuine (Blazer & Hybels, 2005). One issue that complicates analysis of late-life depression is that many physical disorders become increasingly prevalent in old age, making boundaries with depression sometimes unclear and raising the possibility that depression is under-estimated because it is confused with the symptoms of physical disorders (Drayer et al., 2005). This issue is complicated by the fact that some somatic disorders that increase with age can induce depression (Bremmer et al., 2008; Salaycik et al., 2007) while late-life depression can increase risk of some physical disorders (Bremmer et al., 2007; Petronijevic et al., 2008). In an effort to shed light on the possible age-related under-estimation of depression in epidemiological studies due to confounding with physical disorders, we analyzed age-related changes in associations of physical disorders with DSM-IV major depressive episodes (MDE) in the National Comorbidity Survey Replication (NCS-R) (Kessler & Merikangas, 2004). Parallel analysis was carried out with comorbidity between MDE and other DSM-IV mental disorders to determine if the patterns for physical disorders are unique or the same as for mental disorders. MDE was defined without either organic exclusions or diagnostic hierarchy rules to facilitate investigation of comorbidity. Our primary aims were to see if the estimated prevalence of MDE declines with age and to evaluate the extent to which comorbidity of MDE with other disorders changes with age. In studying comorbidity, we focused on associations rather than conditional prevalence, as data on age-related changes in prevalence exist (Blazer et al., 1987; Kennedy et al., 1990) but not data on age-related changes in associations. An examination of these associations is of interest because we would expect them to increase with age if the assessment of MDE is confounded by physical disorders. As a preliminary to the analysis of comorbidity, we examined basic MDE prevalence by age to show that an inverse age-MDE relationship does, in fact, exist in the NCS-R. We then examined age differences in the ratios of recent (30-day and 12-month) to lifetime prevalence, expecting that recall bias would produce higher ratios among elderly than younger respondents whereas substantive patterns would produce the opposite pattern. We also investigated whether MDE age-of-onset distributions differ by age, expecting that recall bias would result in these distributions being skewed more to the right among older than younger respondents. We then compared age-related differences in median numbers of lifetime MDE episodes among respondents with a history of MDE, expecting that recall bias would result in these values not increasing with age in a substantively plausible way. We then examined age differences in the persistence and severity of 12-month MDE, which we assumed would be less influenced by recall bias than data on lifetime MDE. We are unaware of any previous attempt to investigate these specifications in the context of an analysis of comorbidity between MDE and other disorders.

Outcome over seven years of healthy adults with and without subjective cognitive impairment.

Abstract: Background Subjective cognitive impairment (SCI) in older persons without manifest symptomatology is a common condition with a largely unclear prognosis. We hypothesized that (1) examining outcome for a sufficient period by using conversion to mild cognitive impairment (MCI) or dementia would clarify SCI prognosis, and (2) with the aforementioned procedures, the prognosis of SCI subjects would differ significantly from that of demographically matched healthy subjects, free of SCI, termed no cognitive impairment (NCI) subjects. Methods A consecutive series of healthy subjects, aged ≥40 years, presenting with NCI or SCI to a brain aging and dementia research center during a 14-year interval, were studied and followed up during an 18-year observation window. The study population (60 NCI, 200 SCI, 60% female) had a mean age of 67.2 ± 9.1 years, was well-educated (mean, 15.5 ± 2.7 years), and cognitively normal (Mini-Mental State Examination, 29.1 ± 1.2). Results A total of 213 subjects (81.9% of the study population) were followed up. Follow-up occurred during a mean period of 6.8 ± 3.4 years, and subjects had a mean of 2.9 ± 1.6 follow-up visits. Seven NCI (14.9%) and 90 SCI (54.2%) subjects declined ( P P = .0003). Conclusions These results indicate that SCI in subjects with normal cognition is a harbinger of further decline in most subjects during a 7-year mean follow-up interval. Relevance for community populations should be investigated, and prevention studies in this at-risk population should be explored.

Recent developments in gravity-wave effects in climate models and the global distribution of gravity-wave momentum flux from observations and models

Abstract: Recent observational and theoretical studies of the global properties of small-scale atmospheric gravity waves have highlighted the global effects of these waves on the circulation from the surface to the middle atmosphere. The effects of gravity waves on the large-scale circulation have long been treated via parametrizations in both climate and weather-forecasting applications. In these parametrizations, key parameters describe the global distributions of gravity-wave momentum flux, wavelengths and frequencies. Until recently, global observations could not define the required parameters because the waves are small in scale and intermittent in occurrence. Recent satellite and other global datasets with improved resolution, along with innovative analysis methods, are now providing constraints for the parametrizations that can improve the treatment of these waves in climate-prediction models. Research using very-high-resolution global models has also recently demonstrated the capability to resolve gravity waves and their circulation effects, and when tested against observations these models show some very realistic properties. Here we review recent studies on gravity-wave effects in stratosphere-resolving climate models, recent observations and analysis methods that reveal global patterns in gravity-wave momentum fluxes and results of very-high-resolution model studies, and we outline some future research requirements to improve the treatment of these waves in climate simulations. Copyright © 2010 Royal Meteorological Society and Crown in the right of Canada