526 research outputs found

    HST Grism Observations of a Gravitationally Lensed Redshift 10 Galaxy

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    We present deep spectroscopic observations of a Lyman-break galaxy candidate (hereafter MACS1149-JD) at z9.5z\sim9.5 with the Hubble\textit{Hubble} Space Telescope (HST\textit{HST}) WFC3/IR grisms. The grism observations were taken at 4 distinct position angles, totaling 34 orbits with the G141 grism, although only 19 of the orbits are relatively uncontaminated along the trace of MACS1149-JD. We fit a 3-parameter (zz, F160W mag, and Lyα\alpha equivalent width) Lyman-break galaxy template to the three least contaminated grism position angles using an MCMC approach. The grism data alone are best fit with a redshift of zgrism=9.530.60+0.39z_{\mathrm{grism}}=9.53^{+0.39}_{-0.60} (68%68\% confidence), in good agreement with our photometric estimate of zphot=9.510.12+0.06z_{\mathrm{phot}}=9.51^{+0.06}_{-0.12} (68%68\% confidence). Our analysis rules out Lyman-alpha emission from MACS1149-JD above a 3σ3\sigma equivalent width of 21 \AA{}, consistent with a highly neutral IGM. We explore a scenario where the red Spitzer\textit{Spitzer}/IRAC [3.6][4.5][3.6] - [4.5] color of the galaxy previously pointed out in the literature is due to strong rest-frame optical emission lines from a very young stellar population rather than a 4000 \AA{} break. We find that while this can provide an explanation for the observed IRAC color, it requires a lower redshift (z9.1z\lesssim9.1), which is less preferred by the HST\textit{HST} imaging data. The grism data are consistent with both scenarios, indicating that the red IRAC color can still be explained by a 4000 \AA{} break, characteristic of a relatively evolved stellar population. In this interpretation, the photometry indicate that a 34035+29340^{+29}_{-35} Myr stellar population is already present in this galaxy only 500 Myr\sim500~\mathrm{Myr} after the Big Bang.Comment: Accepted to ApJ. This is the accepted versio

    Promoting Physical Activity in Middle School Girls: Trial of Activity for Adolescent Girls

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    Background - Physical activity is important for weight control and good health; however, activity levels decline in the adolescent years, particularly in girls. Design - Group randomized controlled trial. Setting/participants - Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States. Random, cross-sectional samples were drawn within schools: 6th graders in 2003 (n=1721) and 8th graders in 2005 (n=3504) and 2006 (n=3502). Intervention - A 2-year study-directed intervention (fall 2003 to spring 2005) targeted schools, community agencies, and girls to increase opportunities, support, and incentives for increased physical activity. Components included programs linking schools and community agencies, physical education, health education, and social marketing. A third-year intervention used school and community personnel to direct intervention activities. Main outcome measures - The primary outcome, daily MET-weighted minutes of moderate-to-vigorous physical activity (MET-weighted MVPA), was assessed using accelerometry. Percent body fat was assessed using anthropometry. Results - After the staff-directed intervention (pre-stated primary outcome), there were no differences (mean=-0.4, 95% CI=-8.2 to 7.4) in adjusted MET-weighted MVPA between 8th-grade girls in schools assigned to intervention or control. Following the Program Champion-directed intervention, girls in intervention schools were more physically active than girls in control schools (mean difference 10.9 MET-weighted minutes of MVPA, 95% CI=0.52-21.2). This difference is about 1.6 minutes of daily MVPA or 80 kcal per week. There were no differences in fitness or percent body fat at either 8th-grade timepoint. Conclusion - A school-based, community-linked intervention modestly improved physical activity in girls

    Objectively Assessed Associations between Physical Activity and Body Composition in Middle-School Girls: The Trial of Activity for Adolescent Girls

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    Declining levels of physical activity probably contribute to the increasing prevalence of overweight in US youth. In this study, the authors examined cross-sectional and longitudinal associations between physical activity and body composition in sixth- and eighth-grade girls. In 2003, girls were recruited from six US states as part of the Trial of Activity for Adolescent Girls. Physical activity was measured using 6 days of accelerometry, and percentage of body fat was calculated using an age- and ethnicity-specific prediction equation. Sixth-grade girls with an average of 12.8 minutes of moderate-to-vigorous physical activity (MVPA) per day (15th percentile) were 2.3 times (95% confidence interval: 1.52, 3.44) more likely to be overweight than girls with 34.7 minutes of MVPA per day (85th percentile), and their percent body fat was 2.64 percentage points greater (95% confidence interval: 1.79, 3.50). Longitudinal analyses showed that percent body fat increased 0.28 percentage points less in girls with a 6.2-minute increase in MVPA than in girls with 4.5-minute decrease (85th and 15th percentiles of change). Associations between MVPA in sixth grade and incidence of overweight in eighth grade were not detected. More population-based research using objective physical activity and body composition measurements is needed to make evidence-based physical activity recommendations for US youth

    Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review.

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    INTRODUCTION: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. PRESENTATION OF CASE: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. DISCUSSION: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. CONCLUSION: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor

    Ketogenic diet as a glycine lowering therapy in nonketotic hyperglycinemia and impact on brain glycine levels

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    BACKGROUND: Nonketotic hyperglycinemia (NKH) is a severe neurometabolic disorder characterized by increased glycine levels. Current glycine reduction therapy uses high doses of sodium benzoate. The ketogenic diet (KD) may represent an alternative method of glycine reduction. AIM: We aimed to assess clinical and biochemical effects of two glycine reduction strategies: high dose benzoate versus KD with low dose benzoate. METHODS: Six infants with NKH were first treated with high dose benzoate therapy to achieve target plasma glycine levels, and then switched to KD with low dose benzoate. They were evaluated as clinically indicated by physical examination, electroencephalogram, plasma and cerebral spinal fluid amino acid levels. Brain glycine levels were monitored by magnetic resonance spectroscopy (MRS). RESULTS: Average plasma glycine levels were significantly lower with KD compared to benzoate monotherapy by on average 28%. Two infants underwent comparative assessments of brain glycine levels via serial MRS. A 30% reduction of brain glycine levels was observed in the basal ganglia and a 50% reduction in the white matter, which remained elevated above normal, and was equivalent between the KD and high dose benzoate therapies. CSF analysis obtained while participants remained on the KD showed a decrease in glycine, serine and threonine levels, reflecting their gluconeogenetic usage. Clinically, half the patients had seizure reduction on KD, otherwise the clinical impact was variable. CONCLUSION: KD is an effective glycine reduction method in NKH, and may provide a more consistent reduction in plasma glycine levels than high-dose benzoate therapy. Both high-dose benzoate therapy and KD equally reduced but did not normalize brain glycine levels even in the setting of low-normal plasma glycine

    Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

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    Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

    Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma

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    Purpose:; Lobular carcinoma; in situ; (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.; Experimental Design:; We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas; in situ; (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.; Results:; WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with; CDH1; mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.; Conclusions:; Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions
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