Reading Attitudes and Perceptions of 7th-8th Grade Students

The information gathered on a reading attitude and perception survey of 370 middle schools students in the 7th and 8th grades over a three year period (1991-1994) is described below

Longitudinal cohort of HIV-negative transgender women of colour in New York City: protocol for the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study.

IntroductionIn the USA, transgender women are among the most vulnerable to HIV. In particular, transgender women of colour face high rates of infection and low uptake of important HIV prevention tools, including pre-exposure prophylaxis (PrEP). This paper describes the design, sampling methods, data collection and analyses of the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study. In collaboration with communities of transgender women of colour, TURNNT aims to explore the complex social and environmental (ie, neighbourhood) structures that affect HIV prevention and other aspects of health in order to identify avenues for intervention.Methods and analysesTURNNT is a prospective cohort study, which will recruit 300 transgender women of colour (150 Black/African American, 100 Latina and 50 Asian/Pacific Islander participants) in New York City. There will be three waves of data collection separated by 6 months. At each wave, participants will provide information on their relationships, social and sexual networks, and neighbourhoods. Global position system technology will be used to generate individual daily path areas in order to estimate neighbourhood-level exposures. Multivariate analyses will be conducted to assess cross-sectional and longitudinal, independent and synergistic associations of personal relationships (notably individual social capital), social and sexual networks, and neighbourhood factors (notably neighbourhood-level social cohesion) with PrEP uptake and discontinuation.Ethics and disseminationThe TURNNT protocol was approved by the Columbia University Institutional Review Board (reference no. AAAS8164). This study will provide novel insights into the relationship, network and neighbourhood factors that influence HIV prevention behaviours among transgender women of colour and facilitate exploration of this population's health and well-being more broadly. Through community-based dissemination events and consultation with policy makers, this foundational work will be used to guide the development and implementation of future interventions with and for transgender women of colour

Effectiveness of early compared with conservative rehabilitation for patients having rotator cuff repair surgery: an overview of systematic reviews

Aim/objective The aim is to critically analyse and discuss the current literature and determine the effectiveness of ehabilitation for patients after surgical repair of rotator cuff tears for range of motion (ROM), pain, functional status and retear rates; in addition, an update of new literature is included. Design Overview of systematic reviews. Data sources A search was performed with no restrictions to date of publication and language in the following databases: EBSCO, AMED, CINAHL, SPORTDiscus, EMBASE, Cochrane, LILACS, MEDLINE, PEDro, Scielo, SCOPUS and Web of Knowledge. The PRISMA guideline was followed to develop this review and the R-AMSTAR tool was used for critical appraisal of included reviews. Eligibility criteria Only systematic reviews and randomised controlled trials (RCTs) comparing the effectiveness of early with conservative rehabilitation, after surgical repair of the rotator cuff, were included. Moreover, the studies should report ROM, pain, functional status and/or retears rates before and after 3–24 months of the surgery. Results 10 systematic reviews and 11 RCTs were included for the final analysis. Conflicting results and conclusions were presented by the systematic reviews, the use of primary studies varied; also the methodological quality of the reviews was diverse. This updated review, with new meta-analysis, showed no difference for function, pain, ROM or retears ratio between early and conservative rehabilitation. Summary/Conclusions Early mobilisation may be beneficial, particularly for small and medium tears; however, more studies with higher quality are required, especially for patients with large tears who have been given less attention

Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies

IKAROS is a transcription factor forming homo- and heterodimers and regulating lymphocyte development and function. Germline mutations affecting the IKAROS N-terminal DNA binding domain, acting in a haploinsufficient or dominant-negative manner, cause immunodeficiency. Herein, we describe 4 germline heterozygous IKAROS variants affecting its C-terminal dimerization domain, via haploinsufficiency, in 4 unrelated families. Index patients presented with hematologic disease consisting of cytopenias (thrombocytopenia, anemia, neutropenia)/Evans syndrome and malignancies (T-cell acute lymphoblastic leukemia, Burkitt lymphoma). These dimerization defective mutants disrupt homo- and heterodimerization in a complete or partial manner, but they do not affect the wild-type allele function. Moreover, they alter key mechanisms of IKAROS gene regulation, including sumoylation, protein stability, and the recruitment of the nucleosome remodeling and deacetylase complex; none affected in N-terminal DNA binding defects. These C-terminal dimerization mutations are largely associated with hematologic disorders, display dimerization haploinsufficiency and incomplete clinical penetrance, and differ from previously reported allelic variants in their mechanism of action. Dimerization mutants contribute to the growing spectrum of IKAROS-associated diseases displaying a genotype-phenotype correlation

Structural, mechanistic and regulatory studies of serine palmitoyltransferase

SLs (sphingolipids) are composed of fatty acids and a polar head group derived from l-serine. SLs are essential components of all eukaryotic and many prokaryotic membranes but S1P (sphingosine 1-phosphate) is also a potent signalling molecule. Recent efforts have sought to inventory the large and chemically complex family of SLs (LIPID MAPS Consortium). Detailed understanding of SL metabolism may lead to therapeutic agents specifically directed at SL targets. We have studied the enzymes involved in SL biosynthesis; later stages are species-specific, but all core SLs are synthesized from the condensation of l-serine and a fatty acid thioester such as palmitoyl-CoA that is catalysed by SPT (serine palmitoyltransferase). SPT is a PLP (pyridoxal 5'-phosphate)-dependent enzyme that forms 3-KDS (3-ketodihydrosphingosine) through a decarboxylative Claisen-like condensation reaction. Eukaryotic SPTs are membrane-bound multi-subunit enzymes, whereas bacterial enzymes are cytoplasmic homodimers. We use bacterial SPTs (e. g. from Sphingomonas) to probe their structure and mechanism. Mutations in human SPT cause a neuropathy [HSAN1 (hereditary sensory and autonomic neuropathy type 1)], a rare SL metabolic disease. How these mutations perturb SPT activity is subtle and bacterial SPT mimics of HSAN1 mutants affect the enzyme activity and structure of the SPT dimer. We have also explored SPT inhibition using various inhibitors (e. g. cycloserine). A number of new subunits and regulatory proteins that have a direct impact on the activity of eukaryotic SPTs have recently been discovered. Knowledge gained from bacterial SPTs sheds some light on the more complex mammalian systems. In the present paper, we review historical aspects of the area and highlight recent key developments.</p

Reaching the Oldest Stars beyond the Local Group: Ancient Star Formation in UGC 4483

We present new WFC3/UVIS observations of UGC 4483, the closest example of a metal-poor blue compact dwarf galaxy, with a metallicity of Z ≃ 1/15 Z⊙ and located at a distance of D ≃ 3.4 Mpc. The extremely high quality of our new data allows us to clearly resolve the multiple stellar evolutionary phases populating the color-magnitude diagram (CMD), to reach more than 4 mag deeper than the tip of the red giant branch, and to detect for the first time core He-burning stars with masses ≲2 M⊙, populating the red clump and possibly the horizontal branch (HB) of the galaxy. By applying the synthetic CMD method to our observations, we determine an average star formation rate over the whole Hubble time of at least $(7.01\pm 0.44)\times {10}^{-4}$ ${M}_{\odot }\,{{yr}}^{-1}$ , corresponding to a total astrated stellar mass of $(9.60\pm 0.61)\times {10}^{6}$ M⊙, 87% of which went into stars at epochs earlier than 1 Gyr ago. With our star formation history recovery method we find the best fit with a distance modulus of DM = 27.45 ± 0.10, slightly lower than previous estimates. Finally, we find strong evidence of an old (≳10 Gyr) stellar population in UGC 4483 thanks to the detection of an HB phase and the identification of six candidate RR Lyrae variable stars. * Based on observations obtained with the NASA/ESA Hubble Space Telescope at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy under NASA Contract NAS 5-26555