Influence of Proportional Number Relationships on Item Accessibility and Students’ Strategies

Extensive evidence points to the need for mathematics instruction to tap into students’ informal understandings in order to conceptually develop formal mathematical ideas (Ahl, Moore, & Dixon, 1992; Freudenthal, 1973, 1991; Treffers, 1987). Contextual problems are a common means of helping students access their informal mathematical ideas (Lamon, 1993; Moore & Carlson, 2012). However, to successfully use context in this manner, we must ensure these problems are accessible to students and have the potential to promote connections to deeper or more formal mathematics (Jackson, Garrison, Wilson, Gibbons, & Shahan, 2013; Stein, Smith, Henningsen, & Silver, 2000). There is thus a need for research to identify what characteristics make contextual tasks accessible to students as a point of entry and useful for educators in analyzing and pressing students’ thinking

Estimating probability of germline mismatch repair mutations in colorectal cancer patients with microsatellite stable tumors

http://deepblue.lib.umich.edu/bitstream/2027.42/112938/1/13053_2011_Article_206.pd

The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore

M11L, an antiapoptotic protein essential for the virulence of the myxoma poxvirus, is targeted to mitochondria and prevents the loss of mitochondrial membrane potential that accompanies cell death. In this study we show, using a cross-linking approach, that M11L physically associates with the mitochondrial peripheral benzodiazepine receptor (PBR) component of the permeability transition (PT) pore. Close association of M11L and the PBR is also indicated by fluorescence resonance energy transfer (FRET) analysis. Stable expression of M11L prevents the release of mitochondrial cytochrome c induced by staurosporine or protoporphyrin IX (PPIX), a ligand of the PBR. Transiently expressed M11L also prevents mitochondrial membrane potential loss induced by PPIX, or induced by staurosporine in combination with PK11195, another ligand of the PBR. Myxoma virus infection and the associated expression of early proteins, including M11L, protects cells from staurosporine- and Fas-mediated mitochondrial membrane potential loss and this effect is augmented by the presence of PBR. We conclude that M11L regulates the mitochondrial permeability transition pore complex, most likely by direct modulation of the PBR

A Victor's History: A Comparative Analysis of the Labour Historiography of Indonesia's New Order

Some observers have identified a common pattern in developing countries whereby unions are transformed from a political force valued for their contribution to the struggle for independence to a state-sponsored ‘tool of development’. A less well-explored question concerns the harnessing of labour historiography to justify such transitions. As this article shows, Suharto’s New Order (1966–98) undertook a conscious and purposeful rewriting of Indonesian labour history in support of a single vehicle of labour representation organized around a narrative of the dangers of political unionism and designed to control and harness the industrial workforce in the name of economic development

First Sample of Hα\alpha+[O III] λ\lambda5007 Line Emitters at z>6z > 6 through JWST/NIRCam Slitless Spectroscopy: Physical Properties and Line Luminosity Functions

We present a sample of four emission-line galaxies at $z=6.11-6.35$ that were serendipitously discovered using the commissioning data for the JWST/NIRCam wide-field slitless spectroscopy (WFSS) mode. One of them (at $z=6.11$) has been reported previously while the others are new discoveries. These sources are selected by the secure detections of both [O III] $\lambda$5007 and H$\alpha$ lines with other fainter lines tentatively detected in some cases (e.g., [O II] $\lambda$3727, [O III] $\lambda$4959 and [N II] $\lambda$6583). In the [O III]/H$\beta$ - [N II]/H$\alpha$ Baldwin-Phillips-Terlevich diagram, these galaxies occupy the same parameter space as that of $z\sim2$ star-forming galaxies, indicating that they have been enriched rapidly to sub-solar metallicities ($\sim$0.6 $Z_{\odot}$), similar to galaxies with comparable stellar masses at much lower redshifts. The detection of strong H$\alpha$ lines suggests a higher ionizing photon production efficiency within galaxies in the early Universe. We find brightening of the [O III] $\lambda$5007 line luminosity function (LF) from $z=3$ to 6, and no or weak redshift evolution of the H$\alpha$ line LF from $z=2$ to 6. Both LFs are under-predicted at $z\sim6$ by a factor of $\sim$10 in certain cosmological simulations. This further indicates a global Ly$\alpha$ photon escape fraction of 5-7% at $z\sim6$, much lower than previous estimates through the comparison of the UV-derived star-formation rate density and Ly$\alpha$ luminosity density. Our sample recovers $88^{+164}_{-57}$% of $z=6.0-6.6$ galaxies in the survey volume with stellar masses greater than $5\times10^8$ $M_{\odot}$, suggesting the ubiquity of strong H$\alpha$ and [O III] line emitters in the Epoch of Reionization, which will be further uncovered in the era of JWST.Comment: 25 pages, 11 figures, submitted to Ap

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy

Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome