200 research outputs found

    Independent and Combined Effects of Heatwaves and PM2.5 on Preterm Birth in Guangzhou, China: A Survival Analysis.

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    BACKGROUND: Both extreme heat and air pollution exposure during pregnancy have been associated with preterm birth; however, their combined effects are unclear. OBJECTIVES: Our goal was to estimate the independent and joint effects of heatwaves and fine particulate matter [PM 0) for less extreme heatwaves (i.e., shorter or with relatively low temperature thresholds) but were less than additive (RERIs<0) for more intense heatwaves. CONCLUSIONS: Our research strengthens the evidence that exposure to heatwaves during the final gestational week can independently trigger preterm birth. Moderate heatwaves may also act synergistically with PM2.5 exposure to increase risk of preterm birth, which adds new evidence to the current understanding of combined effects of air pollution and meteorological variables on adverse birth outcomes. https://doi.org/10.1289/EHP5117

    Muon Spin Relaxation Study of (La, Ca)MnO3

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    We report predominantly zero field muon spin relaxation measurements in a series of Ca-doped LaMnO_3 compounds which includes the colossal magnetoresistive manganites. Our principal result is a systematic study of the spin-lattice relaxation rates 1/T_1 and magnetic order parameters in the series La_{1-x}Ca_xMnO_3, x = 0.0, 0.06, 0.18, 0.33, 0.67 and 1.0. In LaMnO_3 and CaMnO_3 we find very narrow critical regions near the Neel temperatures T_N and temperature independent 1/T_1 values above T_N. From the 1/T_1 in LaMnO_3 we derive an exchange integral J = 0.83 meV which is consistent with the mean field expression for T_N. All of the doped manganites except CaMnO_3 display anomalously slow, spatially inhomogeneous spin-lattice relaxation below their ordering temperatures. In the ferromagnetic (FM) insulating La_{0.82}Ca_{0.18}MnO_3 and ferromagnetic conducting La_{0.67}Ca_{0.33}MnO_3 systems we show that there exists a bi-modal distribution of \muSR rates \lambda_f and \lambda_s associated with relatively 'fast' and 'slow' Mn fluctuation rates, respectively. A physical picture is hypothesized for these FM phases in which the fast Mn rates are due to overdamped spin waves characteristic of a disordered FM, and the slower Mn relaxation rates derive from distinct, relatively insulating regions in the sample. Finally, likely muon sites are identified, and evidence for muon diffusion in these materials is discussed.Comment: 21 pages, 17 figure

    A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients

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    <p>Abstract</p> <p>Background</p> <p>Diabetic neuropathy (DN) is a common complication of diabetes that has significant economic burden, especially for patients with comorbid depression or anxiety. This study examines and quantifies factors associated with healthcare costs among patients diagnosed with diabetic neuropathy (DN) with or without a comorbid diagnosis of depression or anxiety (DA) using retrospective administrative claims data. No study has examined the differences in economic outcomes depending on the presence of comorbid DA disorders.</p> <p>Methods</p> <p>Over-age-18 individuals with 1+ diagnosis of DN in 2005 were selected. The first observed DN claim was considered the "index date." All individuals had a 12-month pre-index and follow-up period. For both under-age-65 commercially insured and over-age-65 individuals with employer-sponsored Medicare supplemental insurance, we constructed 2 subgroups for individuals with DA (DN-DA) or without (DN-only). Patients' clinical characteristics over pre-index period were compared. Multivariate regressions were performed to assess whether DN-DA patients had higher utilization of healthcare resources and costs than DN-only patients, controlling for demographic and clinical characteristics.</p> <p>Results</p> <p>We identified 16,831 DN-only and 1,699 DN-DA patients in the Medicare supplemental cohort, as well as 17,205 and 3,105 in the commercially insured. DN-DA patients had higher prevalence of diabetes-related comorbidities for cardiovascular disease, cerebrovascular/peripheral vascular disease, nephropathy, obesity, and hypoglycemic events than DN-only patients (all p < 0.05). Controlling for differences in demographic and clinical characteristics, DN-DA patients had 9,235(p<0.05)highertotalhealthcarecoststhanpatientswithDNonlyamongthosewithMedicaresupplementalcoverage(9,235 (p < 0.05) higher total healthcare costs than patients with DN-only among those with Medicare supplemental coverage (26,718 vs. 17,483),and17,483), and 10,389 (p < 0.05) more total costs among commercially insured (29,775vs.29,775 vs. 19,386). Factors associated with increased costs included insurance type, geographical region, diabetes-related comorbidities, and insulin therapy.</p> <p>Conclusion</p> <p>These findings indicate that the healthcare costs were significantly higher for DN patients with depression or anxiety relative to those without such comorbid disorders.</p

    Theory and phenomenology of two-Higgs-doublet models

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    We discuss theoretical and phenomenological aspects of two-Higgs-doublet extensions of the Standard Model. In general, these extensions have scalar mediated flavour changing neutral currents which are strongly constrained by experiment. Various strategies are discussed to control these flavour changing scalar currents and their phenomenological consequences are analysed. In particular, scenarios with natural flavour conservation are investigated, including the so-called type I and type II models as well as lepton-specific and inert models. Type III models are then discussed, where scalar flavour changing neutral currents are present at tree level, but are suppressed by either specific ansatze for the Yukawa couplings or by the introduction of family symmetries. We also consider the phenomenology of charged scalars in these models. Next we turn to the role of symmetries in the scalar sector. We discuss the six symmetry-constrained scalar potentials and their extension into the fermion sector. The vacuum structure of the scalar potential is analysed, including a study of the vacuum stability conditions on the potential and its renormalization-group improvement. The stability of the tree level minimum of the scalar potential in connection with electric charge conservation and its behaviour under CP is analysed. The question of CP violation is addressed in detail, including the cases of explicit CP violation and spontaneous CP violation. We present a detailed study of weak basis invariants which are odd under CP. A careful study of spontaneous CP violation is presented, including an analysis of the conditions which have to be satisfied in order for a vacuum to violate CP. We present minimal models of CP violation where the vacuum phase is sufficient to generate a complex CKM matrix, which is at present a requirement for any realistic model of spontaneous CP violation.Comment: v3: 180 pages, 506 references, new chapter 7 with recent LHC results; referee comments taken into account; submitted to Physics Report

    Protection from the 2009 H1N1 Pandemic Influenza by an Antibody from Combinatorial Survivor-Based Libraries

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    Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06) against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 “Swine” H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population

    Saving the world’s terrestrial megafauna

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    From the late Pleistocene to the Holocene, and now the so called Anthropocene, humans have been driving an ongoing series of species declines and extinctions (Dirzo et al. 2014). Large-bodied mammals are typically at a higher risk of extinction than smaller ones (Cardillo et al. 2005). However, in some circumstances terrestrial megafauna populations have been able to recover some of their lost numbers due to strong conservation and political commitment, and human cultural changes (Chapron et al. 2014). Indeed many would be in considerably worse predicaments in the absence of conservation action (Hoffmann et al. 2015). Nevertheless, most mammalian megafauna face dramatic range contractions and population declines. In fact, 59% of the world’s largest carnivores (≥ 15 kg, n = 27) and 60% of the world’s largest herbivores (≥ 100 kg, n = 74) are classified as threatened with extinction on the International Union for the Conservation of Nature (IUCN) Red List (supplemental table S1 and S2). This situation is particularly dire in sub-Saharan Africa and Southeast Asia, home to the greatest diversity of extant megafauna (figure 1). Species at risk of extinction include some of the world’s most iconic animals—such as gorillas, rhinos, and big cats (figure 2 top row)—and, unfortunately, they are vanishing just as science is discovering their essential ecological roles (Estes et al. 2011). Here, our objectives are to raise awareness of how these megafauna are imperiled (species in supplemental table S1 and S2) and to stimulate broad interest in developing specific recommendations and concerted action to conserve them

    Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance

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    <p>Abstract</p> <p>Background</p> <p>Subsets of cells with stem-like properties have been previously isolated from human epithelial cancers and their resistance to apoptosis-inducing stimuli has been related to carcinoma recurrence and treatment failure. The aim of this study was to investigate the mechanisms of resistance to apoptosis-inducing agents of cells with stem-like properties in both normal and malignant human epithelia.</p> <p>Methods</p> <p>Cells isolated from fresh human head and neck carcinomas (n = 11), cell lines derived from head and neck, prostate and breast human carcinomas (n = 7), and from normal human oral mucosa (n = 5), were exposed to various apoptosis-inducing stimuli (UV, Tumour Necrosis Factor, Cisplatin, Etoposide, and Neocarzinostatin). Flow cytometry for CD44 and epithelial-specific antigen (ESA) expression, colony morphology, tumour sphere formation and rapid adherence assays were used to identify the subset of cells with stem-like properties. Apoptosis, cell cycle and expression of various cell cycle checkpoint proteins were assessed (Western Blot, qPCR). The role of G2-checkpoint regulators Chk1 and Chk2 was investigated by use of debromohymenialdisine (DBH) and siRNA.</p> <p>Results</p> <p>In both cancer biopsies and carcinoma cell lines a subset of CD44<sup>high </sup>cells showed increased clonogenicity, a significantly lower rate of apoptosis, and a significantly higher proportion of cells in the G2-phase of the cell cycle. An inverse correlation between the percentage of cells in G2-phase and the rate of apoptosis was found. Pulse-chase with iododeoxyuridine (IdU) demonstrated that CD44<sup>high </sup>carcinoma cells spent longer time in G2, even in un-treated controls. These cells expressed higher levels of G2 checkpoint proteins, and their release from G2 with BDH or Chk1 siRNA increased their rate of apoptosis. Low passage cultures of normal keratinocytes were also found to contain a subset of CD44<sup>high </sup>cells showing increased clonogenicity, and a similar pattern of G2-block associated with apoptotic resistance.</p> <p>Conclusions</p> <p>These data indicate that both normal and malignant human epithelial cells with stem-like properties show greater resistance to apoptosis associated with extended G2 cell cycle phase, and that this property is not a consequence of neoplastic transformation. Targeting G2 checkpoint proteins releases these cells from the G2-block and makes them more prone to apoptosis, implying an opportunity for improved therapeutic approaches.</p
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