Bringing College Classes to High School

Recent education reforms have focused heavily on increasing academic rigor for secondary students attending public schools with a goal of improved academic outcomes for all students. A common practice for increasing rigor school-wide is the adoption of college-level curriculums such as dual-credit, Advanced Placement, and the International Baccalaureate in U.S public secondary schools. This study examined the relationship between the implementation of one or more college-level curriculum(s) in a public secondary school and overall student academic achievement. Academic achievement was measured by student performance on the Washington state standardized End of Course exam in Biology and the Smarter Balanced exams in English Language Arts and Mathematics, while controlling for demographic difference between schools (N = 559). Additionally, this study examined the relationship between the implementation of a college-level curriculum and on-time graduation rates for the class of 2015, also controlling for demographic differences between schools (N = 559). A generalized linear mixed model was utilized to examine school-level exam data and demographic data from the Washington state Office of Superintendent of Public Instruction for the 2014-2015 academic year to assess whether the presence of a college-level curriculum in a secondary school setting influenced academic achievement and on-time graduation. Results of the GLMMs suggested that the presence of a college-level curriculum in the school does increases the odds of passing the EOC Biology exam but does not increase the odds of passing the SBA ELA exam or passing the SBA Math exam. Results of the GLMMs suggested that the presence of a college-level curriculum in the school also increases the odds of graduating on time

Influence of grain direction in vibrational wood welding

Wood grain orientation differences in the two surfaces to be bonded yield bondlines of different strength in no-adhesives wood welding. Longitudinal wood grain bonding of tangential and radial wood sections yields an approximately 10% difference in strength results of the joint. Cross-grain (±90°) bonding yields instead a much lower strength result, roughly half that observed for pieces bonded with the grain parallel to each other. These differences can be explained by the very marked effect that homogeneity of fibre orientation is known to have on fibre–matrix composites. Oak yields lower results than beech and maple and is more sensitive to welding conditions. Differences in both anatomical and wood constituent composition can account for this difference in performance. Contrary to the other wood species, oak always presents joint bondlines where little or no increase in density at the interface is noticed. This explains its somewhat lower strength results. This is based on the different mode of bonding predominant in this species, while the other species present two different modes of bonding. Thus, two types of bondlines are observed by scanning electron microscopy (SEM): (i) bondlines where entangled fibre–matrix composites are formed at the interface and (ii) bondlines in which direct welding of the cell walls occurs, just by fused intercellular material or cell surface material. In this latter case the cells remain flat, without an entangled fibre–matrix composite being formed. This is the almost exclusively predominant case for oak. Both cases and even hybrid cases between the two have also been observed in beech

INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling

<p>Abstract</p> <p>Background</p> <p>The gene encoding integrator complex subunit 6 (<it>INTS6</it>), previously known as deleted in cancer cells 1 (<it>DICE1</it>, OMIM 604331) was found to be frequently affected by allelic deletion and promoter hypermethylation in prostate cancer specimens and cell lines. A missense mutation has been detected in prostate cancer cell line LNCaP. Together, these results suggest <it>INTS6/DICE1 </it>as a putative tumor suppressor gene in prostate cancer. In this study, we examined the growth inhibitory effects of <it>INTS6/DICE1 </it>on prostate cancer cells.</p> <p>Results</p> <p>Markedly decreased <it>INTS6/DICE1 </it>mRNA levels were detected in prostate cancer cell lines LNCaP, DU145 and PC3 as well as CPTX1532 as compared to a cell line derived from normal prostate tissue, NPTX1532. Exogenous re-expression of <it>INTS6/DICE1 </it>cDNA in androgen-independent PC3 and DU145 cell lines substantially suppressed their ability to form colonies <it>in vitro</it>. This growth inhibition was not due to immediate induction of apoptosis. Rather, prostate cancer cells arrested in G1 phase of the cell cycle. Expression profiling of members of the Wnt signaling pathway revealed up-regulation of several genes including disheveled inhibitor CXXC finger 4 (<it>CXXC4</it>), frizzled homologue 7 (<it>FZD7</it>), transcription factor 7-like 1 (<it>TCF7L1</it>), and down-regulation of cyclin D1.</p> <p>Conclusion</p> <p>These results show for the first time a link between <it>INTS6/DICE1 </it>function, cell cycle regulation and cell-cell communication involving members of the Wnt signaling pathway.</p

Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing

MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure–function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer–small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine

Group eye movement desensitization and reprocessing (EMDR) in chronic pain patients

The prevalence of chronic pain is increasing, and conventional pain therapies often have limited efficacy in individuals with high levels of psychological distress and a history of trauma. In this context, the use of Eye Movement Desensitization and Reprocessing (EMDR), an evidence-based psychotherapy approach for the treatment of posttraumatic stress disorder, is becoming increasingly important. EMDR shows promising results, particularly for patients with pain and high levels of emotional distress. Although group therapy is becoming increasingly popular in pain management, EMDR has mainly been studied as an individual treatment. However, a systematic review suggests that group therapy can be an effective tool for improving mental health outcomes, especially when trauma is addressed together. Based on these findings, an outpatient EMDR group program was developed for patients with chronic pain. The program consists of a total of four treatment days with 5–5.5 h therapy sessions each day and provides patients with a supportive environment in which they can learn effective pain management strategies and interact with other patients with similar experiences. Initial pilot evaluations indicate high efficacy and adequate safety for patients with chronic pain

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe