884 research outputs found

    Maximizing Beneficence and Autonomy: Ethical Support for the Use of Non-Pharmacological Methods for Managing Dental Anxiety

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    This article examines advantages associated with nonpharmacological behavioral management techniques and suggests that there are benefits to their use (such as achieving a more lasting solution to the problem of dental anxiety) that are not realized with medication-based interventions. Analyses that use Kantian and existential viewpoints for exploring the use of medication versus behavioral interventions for managing life problems yield parallel conclusions: there are advantages gained by using behavioral interventions that are not always associated with medicationbased interventions. These analyses, taken together with an understanding of the psychology of dental anxiety management, suggest that using nonpharmacological techniques for the management of dental anxiety can maximize adherence-to the ethical principles of beneficence and patient autonomy. The authors discuss the barriers that make nonpharmacological interventions for anxiety management difficult for dentists to routinely use, and suggest that additional training in these methods and increased collaboration with mental health professionals are needed for dentists

    Impact of the COVID-19 Pandemic on the Welfare of Animals in Australia

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    We report on the various responses in Australia during 2020 to minimize negative impacts of the COVID-19 pandemic on the welfare of animals. Most organizations and individuals with animals under their care had emergency preparedness plans in place for various scenarios; however, the restrictions on human movement to contain the spread of COVID-19, coupled with the economic impact and the health effects of COVID-19 on the skilled workforce, constituted a new threat to animal welfare for which there was no blueprint. The spontaneous formation of a national, multisectoral response group on animal welfare, consisting of more than 34 organizations with animals under their care, facilitated information flow during the crisis, which helped to mitigate some of the shocks to different organizations and to ensure continuity of care for animals during the pandemic. We conclude that animal welfare is a shared responsibility, and accordingly, a multisectoral approach to animal welfare during a crisis is required. Our experience demonstrates that to safeguard animal welfare during crises, nations should consider the following: a national risk assessment, clear communication channels, contingency plans for animal welfare, a crisis response group, and support systems for animal care providers. Our findings and recommendations from the Australian context may inform other countries to ensure that animal welfare is not compromised during the course of unpredictable events

    SN 2022crv: IIb, Or Not IIb: That is the Question

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    We present optical and near-infrared observations of SN~2022crv, a stripped envelope supernova in NGC~3054, discovered within 12 hrs of explosion by the Distance Less Than 40 Mpc Survey. We suggest SN~2022crv is a transitional object on the continuum between SNe Ib and SNe IIb. A high-velocity hydrogen feature (\sim-20,000 -- -16,000 kms1\rm km\,s^{-1}) was conspicuous in SN~2022crv at early phases, and then quickly disappeared around maximum light. By comparing with hydrodynamic modeling, we find that a hydrogen envelope of 103\sim 10^{-3} \msun{} can reproduce the behaviour of the hydrogen feature observed in SN~2022crv. The early light curve of SN~2022crv did not show envelope cooling emission, implying that SN~2022crv had a compact progenitor with extremely low amount of hydrogen. The analysis of the nebular spectra shows that SN~2022crv is consistent with the explosion of a He star with a final mass of \sim4.5 -- 5.6 \msun{} that has evolved from a \sim16 -- 22 \msun{} zero-age main sequence star in a binary system with about 1.0 -- 1.7 \msun{} of oxygen finally synthesized in the core. The high metallicity at the supernova site indicates that the progenitor experienced a strong stellar wind mass loss. In order to retain a small amount of residual hydrogen at such a high metallicity, the initial orbital separation of the binary system is likely larger than \sim1000~R\rm R_{\odot}. The near-infrared spectra of SN~2022crv show a unique absorption feature on the blue side of He I line at \sim1.005~μ\mum. This is the first time that such a feature has been observed in a Type Ib/IIb, and could be due to \ion{Sr}{2}. Further detailed modelling on SN~2022crv can shed light on the progenitor and the origin of the mysterious absorption feature in the near infrared.Comment: 33 pages, 23 figures, submitted to Ap

    Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E

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    Translation of mRNA into protein has a fundamental role in neurodevelopment, plasticity, and memory formation; however, its contribution in the pathophysiology of depressive disorders is not fully understood. We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor 4E), in depression-like behavior in mice. Mice carrying a mutation in eIF4E for the MNK1/2 phosphorylation site (Ser209Ala, Eif4e ki/ki), the Mnk1/2 double knockout mice (Mnk1/2 -/-), or mice treated with the MNK1/2 inhibitor, cercosporamide, displayed anxiety-and depression-like behaviors, impaired serotonin-induced excitatory synaptic activity in the prefrontal cortex, and diminished firing of the dorsal raphe neurons. In Eif4e ki/ki mice, brain IκBα, was decreased, while the NF-κB target, TNFα was elevated. TNFα inhibition in Eif4e ki/ki mice rescued, whereas TNFα administration to wild-type mice mimicked the depression-like behaviors and 5-HT synaptic deficits. We conclude that eIF4E phosphorylation modulates depression-like behavior through regulation of inflammatory responses

    The Eleventh and Twelfth Data Releases of the Sloan Digital Sky Survey: Final Data from SDSS-III

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    The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All of the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 deg2 of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include the measured abundances of 15 different elements for each star. In total, SDSS-III added 5200 deg2 of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 deg2; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra. \ua9 2015. The American Astronomical Society

    Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

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    Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

    Taxonomy based on science is necessary for global conservation

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    The Magnitude of Global Marine Species Diversity

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    Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are ∼226,000 eukaryotic marine species described. More species were described in the past decade (∼20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are ∼170,000 synonyms, that 58,000–72,000 species are collected but not yet described, and that 482,000–741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7–1.0 million marine species. Past rates of description of new species indicate there may be 0.5 ± 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century

    Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

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    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

    The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin.

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    Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo Furthermore, spliceosome inhibitors reduced BRCA1-Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance. Cancer Res; 76(9); 2778-90. ©2016 AACR
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