778 research outputs found

    Dating Violence, Don\u27t Ignore It!

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    Educational leaders have a substantial degree of control over students and generally have a tremendous influence on the decisions that they make. District administrators are already involved in comprehensive efforts to stem sexual harassment, teen violence and bullying; therefore, they may be well positioned to identify and address the problem of teen dating violence. Unfortunately, school district failure to take action is far too common, despite the statutory duty to ensure the safety of all students during school hours and at school sponsored events. School districts can be held liable for student dating violence under Title IX, under 42 U.S.C. §1983 and under Tort liability

    Adolescent Dating Violence: How Should Schools Respond?

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    Educational leaders have a substantial degree of control over students and generally have a tremendous influence on the decisions that they make. District administrators are already involved in comprehensive efforts to stem sexual harassment, teen violence and bullying, therefore, they may be well positioned to identify and address the problem of teen dating violence. Unfortunately, school district failure to take action is far too common, despite the statutory duty to ensure the safety of all students during school hours and at school sponsored events. School districts can be held liable for student dating violence under Title IX, under 42 U.S.C. §1983 and under Tort liability

    Nutritional characterization and storage ability of Salicornia ramosissima and Sarcocornia perennis for fresh vegetable salads

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    The aim of this work was to study the potential of two halophytes for fresh salads. Sarcocornia perennis (SAR) and Salicornia ramosissima (SAL) plant tips were harvested in May and July, and stored at 4 °C for 14 days. At harvest, mineral analyses (Na, K, Mg, Ca, P, N, Fe, Zn, Cu, Pb and Cd), chlorophyll content, protein, β-carotene and ascorbic acid were performed. Color (CIELab), phenolics, antioxidant activity and microbial contamination were measured at harvest and after 14 days storage at 4 °C, and a taste panel evaluated the products. SAL had generally slightly higher values of vitamin C, phenols and carotenoids than SAR. In SAR after 14 days of storage, the levels of phenols and the antioxidant activity were higher than at harvest, both in May and July. The opposite was observed for SAL. In this case, only the antioxidant activity was higher after 14 days of storage. Microbial contamination was very low, not reaching even half of critical limits. Both halophytes had good nutritional value, being suitable for use as fresh salads which can be stored for up to 14 days at 4 °C. SAR seems to be a better source of antioxidants, Ca and Fe than SAL and has less general quality and nutritional value changes from harvest time through cold storage. Fresh tips of both halophytes showed better appearance and nutritional quality when harvested in the early season (May) than at the end of the season (July).This research was funded by the Fundação para a Ciência e Tecnologia-FCT, Portugal, under the projects UIDB/05183/2020 MED and UID/BIA/04325/2013-MEDTBIO.info:eu-repo/semantics/publishedVersio

    CMB-S4 Science Book, First Edition

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    This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

    Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells

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    Background Impaired mineral ion metabolism is a hallmark of CKD–metabolic bone disorder. It can lead to pathologic vascular calcification and is associated with an increased risk of cardiovascular mortality. Loss of calcium-sensing receptor (CaSR) expression in vascular smooth muscle cells exacerbates vascular calcification in vitro. Conversely, vascular calcification can be reduced by calcimimetics, which function as allosteric activators of CaSR. Methods To determine the role of the CaSR in vascular calcification, we characterized mice with targeted Casr gene knockout in vascular smooth muscle cells (SM22αCaSRΔflox/Δflox). Results Vascular smooth muscle cells cultured from the knockout (KO) mice calcified more readily than those from control (wild-type) mice in vitro. However, mice did not show ectopic calcifications in vivo but they did display a profound mineral ion imbalance. Specifically, KO mice exhibited hypercalcemia, hypercalciuria, hyperphosphaturia, and osteopenia, with elevated circulating fibroblast growth factor 23 (FGF23), calcitriol (1,25-D3), and parathyroid hormone levels. Renal tubular α-Klotho protein expression was increased in KO mice but vascular α-Klotho protein expression was not. Altered CaSR expression in the kidney or the parathyroid glands could not account for the observed phenotype of the KO mice. Conclusions These results suggest that, in addition to CaSR’s established role in the parathyroid-kidney-bone axis, expression of CaSR in vascular smooth muscle cells directly contributes to total body mineral ion homeostasis

    The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

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    <p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7<sup>th </sup>and 28<sup>th </sup>day of life. The primary outcomes were mortality between the 7<sup>th </sup>and 28<sup>th </sup>day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p

    Description of the methodology used in an ongoing pediatric care interventional study of children born with cleft lip and palate in South America [NCT00097149]

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    BACKGROUND: The contribution of birth defects, including cleft lip and palate, to neonatal and infant mortality and morbidity is substantial. As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally. METHODS/DESIGN: We are using cleft lip and palate as a sentinel birth defect to evaluate its burden on neonatal and infant health and to assess the effectiveness of systematic pediatric care during the first month and first two years of life in decreasing this burden. The neonatal intervention, consisting of weekly pediatric evaluation and referral to appropriate care, is delivered to about 696 infants born with cleft lip and/or palate in 47 hospitals in South America. Neonatal mortality in this group will be compared to that in a retrospective control group of about 464 infants born with cleft lip and/or palate in the same hospitals. The subgroup of infants with isolated clefts of both the lip and palate (about 264) is also randomized into two groups, intervened and non-intervened, and further followed up over 2 years. Intervened cases are evaluated by pediatricians every three months and referred for appropriate care. The intervened and non-intervened cases will be compared over study outcomes to evaluate the intervention effectiveness. Non-intervened cases are matched and compared to healthy controls to assess the burden of cleft lip and palate. Outcomes include child's neurological and physical development and family social and economic conditions. DISCUSSION: Large-scale clinical trials to improve infant health in developing countries are commonly suggested, making it important to share the methods used in ongoing studies with other investigators implementing similar research. We describe here the content of our ongoing pediatric care study in South America. We hope that this may help researchers targeting this area to plan their studies more effectively and encourage the development of similar research efforts to target other birth defects or infant outcomes such as prematurity and low birth weight

    PDP-1 Links the TGF-β and IIS Pathways to Regulate Longevity, Development, and Metabolism

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    The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1 receptor tyrosine kinase), AGE-1 (PI 3-kinase), and additional downstream serine/threonine kinases that ultimately phosphorylate and negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular signaling homeostasis by counterbalancing kinase activity. However, few phosphatases have been identified that negatively regulate the IIS pathway. Here we identify and characterize pdp-1 as a novel negative modulator of the IIS pathway. We show that PDP-1 regulates multiple outputs of IIS such as longevity, fat storage, and dauer diapause. In addition, PDP-1 promotes DAF-16 nuclear localization and transcriptional activity. Interestingly, genetic epistasis analyses place PDP-1 in the DAF-7/TGF-β signaling pathway, at the level of the R-SMAD proteins DAF-14 and DAF-8. Further investigation into how a component of TGF-β signaling affects multiple outputs of IIS/DAF-16, revealed extensive crosstalk between these two well-conserved signaling pathways. We find that PDP-1 modulates the expression of several insulin genes that are likely to feed into the IIS pathway to regulate DAF-16 activity. Importantly, dysregulation of IIS and TGF-β signaling has been implicated in diseases such as Type 2 Diabetes, obesity, and cancer. Our results may provide a new perspective in understanding of the regulation of these pathways under normal conditions and in the context of disease

    Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

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    Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

    CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

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    CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, rr, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r>0.003r > 0.003 at greater than 5σ5\sigma, or, in the absence of a detection, of reaching an upper limit of r<0.001r < 0.001 at 95%95\% CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447
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