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Levantine scraper, Capoeta damascina is a candidate species for future stock assessments, conservation studies, and hatchery efforts. Herein, we documented embryonic and early larval development, from egg activation to the exogenous feeding period, using morphological and histological landmarks. Embryos were obtained by in vitro fertilization from hormonally induced wild-caught broodstock, and subsequent development was monitored at temperatures coinciding with native conditions. Embryonic development from fertilization to hatch lasted ~105–110 hr. Larvae emerged with unpigmented eyes and body morphology, as well as an undifferentiated digestive tract. The mouth was closed at hatch by the oropharyngeal membrane and opened by the early endogenous feeding period. Trabeculae cartilage, quadrate bone, and Meckel's cartilage of the endoskeleton were present during the endogenous feeding period. During this period, the larvae underwent considerable changes in craniofacial morphology, locomotion, and organogenesis of the digestive tract. The cartilaginous floor of the neurocranium developed and the first four ceratobranchials appeared simultaneously at the end of endogenous feeding period. The digestive tract was differentiated into buccopharynx, esophagus, and small intestine during the endogenous feeding period. The intestinal valve and numerous longitudinal folds at the posterior region of the intestine formed together by the endo–exogenous feeding period. Major developmental events in retinogenesis occurred during the endogenous feeding period. When larvae entered exogenous feeding the mouth was fully-functional. Additionally, liver size and eye diameter increased. Our analysis of embryonic and early larval development in Levantine scraper aligned with other freshwater fishes.  相似文献   
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Evolution should render individuals resistant to stress and particularly to stress experienced by ancestors. However, many studies report negative effects of stress experienced by one generation on the performance of subsequent generations. To assess the strength of such transgenerational effects we propose a strategy aimed at overcoming the problem of type I errors when testing multiple proxies of stress in multiple ancestors against multiple offspring performance traits, and we apply it to a large observational dataset on captive zebra finches (Taeniopygia guttata). We combine clear one-tailed hypotheses with steps of validation, meta-analytic summary of mean effect sizes, and independent confirmatory testing. We find that drastic differences in early growth conditions (nestling body mass 8 days after hatching varied sevenfold between 1.7 and 12.4 g) had only moderate direct effects on adult morphology (95% confidence interval [CI]: r = 0.19–0.27) and small direct effects on adult fitness traits (r = 0.02–0.12). In contrast, we found no indirect effects of parental or grandparental condition (r = −0.017 to 0.002; meta-analytic summary of 138 effect sizes), and mixed evidence for small benefits of matching environments between parents and offspring, as the latter was not robust to confirmatory testing in independent datasets. This study shows that evolution has led to a remarkable robustness of zebra finches against undernourishment. Our study suggests that transgenerational effects are absent in this species, because CIs exclude all biologically relevant effect sizes.  相似文献   
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Background: In March of 2017, dupilumab became the first FDA approved injectable biologic for treatment of moderate-to-severe atopic dermatitis (AD). As the first drug in this class for AD, dupilumab has revolutionized the disease’s treatment and improved patient outcomes significantly. Previous work has demonstrated that dermatologic injectable biologics are not uniformly accessible to patients in the US, and that patients in more rural regions are less likely to have access to these medications. In this study, we aimed to evaluate the early utilization trends of dupilumab for the Medicare population in the first year of its FDA approval (2017). Methods: Retrospective cohort study of the Medicare Provider Utilization and Payment Data. Counties were categorized by Rural-Urban Continuum Codes (RUCC) based on size, extent of urbanization, and proximity to a metropolitan (metro) area as defined by the National Center for Health Statistics Urban-Rural Classification Scheme for Counties. Results: There were 142 individuals who prescribed dupilumab at least 10 times in 2017, 80% of whom were dermatologists. Of these providers, 130 (91.5%) practiced in metropolitan (metro) counties and 12 practiced in non-metro counties. There were 14 cities with two or more dupilumab prescribers, with highest numbers observed in New York, NY (8 providers); Philadelphia, PA (6 providers); Phoenix, AZ (5 providers); and Norfolk, VA (4 providers). Conclusions: There are differences in access to dupilumab in the Medicare population based on geographic location in the US. Trends of decreased access to novel dermatologic biologics in rural areas of the US may begin at their introduction to the market, identifying a potential target for future interventions to equalize access.  相似文献   
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