477 research outputs found

    Male fetal loss in the U.S. following the terrorist attacks of September 11, 2001

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    Background: The secondary sex ratio (i.e., the odds of a male birth) reportedly declines following natural disasters, pollution events, and economic collapse. It remains unclear whether this decline results from an excess of male fetal loss or reduced male conceptions. The literature also does not converge as to whether the terrorist attacks of September 11, 2001 induced "communal bereavement", or the widespread feeling of distress among persons who never met those directly involved in the attacks. We test the communal bereavement hypothesis among gravid women by examining whether male fetal deaths rose above expected levels in the US following September 11, 2001. Methods: We apply interrupted time-series methods to all fetal deaths at or greater than the 20(th) week of gestation in the US from 1996 to 2002. Time-series methods control for trends, seasonality, and other forms of autocorrelation that could induce spurious associations. Results: Results support the hypothesis in that the fetal death sex ratio (i.e., the odds of a male fetal death) increased above its expected value in September 2001. Additional analysis of the secondary sex ratio indirectly supports that the terrorist attacks may have threatened the gestation of male more than female fetuses. Conclusions: Societal responses to events such as September 11, 2001 do not appear confined only to persons who have ever met the deceased. The fetal death sex ratio in the US population may serve as a sentinel indicator of the degree to which pregnant women react to population stressors

    Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

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    Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al

    Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

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    Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma

    A Critical Review of Anti‐Bullying Programs in North American Elementary Schools

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    BACKGROUNDBullying behavior is a concern among school‐aged youth and anti‐bullying programs have been implemented in schools throughout North America. Most anti‐bullying programs are delivered to adolescent youth because antisocial‐aggressive behaviors are typically associated with this developmental stage. This paper is a review of empirically evaluated school‐based bullying prevention and intervention programs in North American elementary schools.METHODSWe conducted a systematic, critical review of bullying prevention programming. Data were analyzed to determine the study method, intervention components, measurement of bullying, aggression, or peer victimization, outcomes measured, and results.RESULTSOur review resulted in the identification of 10 interventions aimed at youth in grades K‐6 enrolled in North American elementary schools. Effective intervention strategies targeted a variety of bullying behaviors using diverse mechanisms and included a school—and community‐wide approach. Direct outcomes of the reviewed evaluations were centered on bullying, aggression, and victimization. Indirect outcomes of review evaluations included strategies for bystanders, school achievement, perceived school safety, and knowledge or attitudes about bullying.CONCLUSIONSRecommendations for promising practices in effective bullying intervention programming are offered. The review concludes with suggestions for supporting school health staff and in‐service teachers drawn from the body of research, and offers direction for future study.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151360/1/josh12814_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151360/2/josh12814.pd

    Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer

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    BACKGROUND: Loss of activity of tumor suppressor genes is considered a fundamental step in a genetic model of carcinogenesis. Altered expression of the p53 and the Deleted in Colon Cancer (DCC) proteins has been described in gastric cancer and this event may have a role in the development of the disease. According to this hypothesis, we investigated the p53 and the DCC proteins expression in different stages of gastric carcinomas. METHODS: An immunohistochemical analysis for detection of p53 and DCC proteins expression was performed in tumor tissue samples of patients with UICC stage I and II gastric cancer. For the purpose of the analysis, the staining results were related to the pathologic data and compared between stage categories. RESULTS: Ninety-four cases of gastric cancer were analyzed. Disease stage categories were pT1N0 in 23 cases, pT2N0 in 20 cases, pT3N0 in 20 cases and pT1-3 with nodal involvment in 31 cases. Stage pT1-2N0 tumors maintained a positive DCC expression while it was abolished in pT3N0 tumors (p <.001). A significant higher proportion of patients with N2 nodal involvement showed DCC negative tumors. In muscular-invading tumors (pT2-3N0) the majority of cases showed p53 overexpression, whereas a significantly higher proportion of cases confined into the mucosa (pT1N0) showed p53 negative tumors. Also, a higher frequency of p53 overexpression was detected in cases with N1 and N2 metastatic lymphnodal involvement. CONCLUSIONS: Altered expression of both DCC and p53 proteins is detectable in gastric carcinomas. It seems that loss of wild-type p53 gene function and consequent p53 overexpression may be involved in early stages of tumor progression while DCC abnormalities are a late event

    Multi-scale investigation of uranium attenuation by arsenic at an abandoned uranium mine, South Terras

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    Detailed mineralogical analysis of soils from the UK’s historical key uranium mine, South Terras, was performed to elucidate the mechanisms of uranium degradation and migration in the 86 years since abandonment. Soils were sampled from the surface (0 – 2 cm) and near-surface (25 cm) in two distinct areas of ore processing activities. Bulk soil analysis revealed the presence of high concentrations of uranium (<1690 ppm), arsenic (1830 ppm) and beryllium (~250 ppm), suggesting pedogenic weathering of the country rock and ore extraction processes to be the mechanisms of uranium ore degradation. Micro-focus XRF analysis indicated the association of uranium with arsenic, phosphate and copper; µ-XRD data confirmed the presence of the uranyl-arsenate minerals metazeunerite (Cu(UO2)2(AsO4)2·8H2O) and metatorbernite (Cu(UO2)2(PO4)2·8H2O) to be ubiquitous. Our data are consistent with the solid solution of these two uranyl-mica minerals, not previously observed at uranium-contaminated sites. Crystallites of uranyl-mica minerals were observed to coat particles of jarosite and muscovite, suggesting that the mobility of uranium from degraded ores is attenuated by co-precipitation with arsenic and phosphate, which was not previously considered at this site

    Postcopulatory sexual selection

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    The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

    Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification

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    INTRODUCTION: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe /PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18-26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812

    Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

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    The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events.Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent.While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.ClinicalTrials.gov NCT00793754
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