New TESOL graduates’ employment experiences and views of teacher education: Report to the Wintec Research Committee following poster presentation at the 9th Community Languages and ESOL (CLESOL) conference, 24—27 September, 2004, Christchurch

In 2003 a new 12-week full time Teaching English to Speakers of Other Languages (TESOL) programme called Certificate in English Language Teaching (Cert ELT) was offered by the Department of Education at the Waikato Institute of Technology (Wintec) for the first time. While other TESOL programmes offered by Wintec are for trained teachers and teacher-aides, the new Cert ELT programme is for those with little or no previous teaching experience. The curriculum development and delivery of Wintec’s TESOL programmes are informed by a constructivist view of learning which has held a prominent focus in educational literature since the late 1980s. This theory of learning sees learners as active participants in the processes of incorporating, synthesising and constructing knowledge within their previous experience (Arlidge, 2000; Zepke, Nugent & Leach 2003). Of particular relevance within TESOL literature is the social constructivist view which claims that a key element in the learning process is that knowledge is socially constructed through dialogue and interaction with others (Randall & Thornton, 2001; Malderez & Bodoczky, 1999; James, 2001). Also relevant is the reflective model of TESOL teacher education as outlined by Wallace (1993) in which trainees participate in a continuous cycle of teaching, observation, reflection and discussion in order to become reflective practitioners. A lack of information concerning what happens to the Cert ELT students once they graduate from the programme motivated the research discussed in this paper. Data collection included a questionnaire and individual interviews. The questionnaire gathered information concerning the graduates' employment destinations, and the interviews focussed on the graduates' retrospective views of those components of the programme associated with a social constructivist view of learning. These components included experiential learning, reflective practice and collaborative practice. It is expected that insights gained from this project will be of interest to other TESOL professionals and teacher educators

Predicting asthma-related crisis events using routine electronic healthcare data

Background There is no published algorithm predicting asthma crisis events (accident and emergency [A&E] attendance, hospitalisation, or death) using routinely available electronic health record (EHR) data. Aim To develop an algorithm to identify individuals at high risk of an asthma crisis event. Design and setting Database analysis from primary care EHRs of people with asthma across England and Scotland. Method Multivariable logistic regression was applied to a dataset of 61 861 people with asthma from England and Scotland using the Clinical Practice Research Datalink. External validation was performed using the Secure Anonymised Information Linkage Databank of 174 240 patients from Wales. Outcomes were ≥1 hospitalisation (development dataset) and asthma-related hospitalisation, A&E attendance, or death (validation dataset) within a 12-month period. Results Risk factors for asthma-related crisis events included previous hospitalisation, older age, underweight, smoking, and blood eosinophilia. The prediction algorithm had acceptable predictive ability with a receiver operating characteristic of 0.71 (95% confidence interval [CI] = 0.70 to 0.72) in the validation dataset. Using a cut-point based on the 7% of the population at greatest risk results in a positive predictive value of 5.7% (95% CI = 5.3% to 6.1%) and a negative predictive value of 98.9% (95% CI = 98.9% to 99.0%), with sensitivity of 28.5% (95% CI = 26.7% to 30.3%) and specificity of 93.3% (95% CI = 93.2% to 93.4%); those individuals had an event risk of 6.0% compared with 1.1% for the remaining population. In total, 18 people would need to be followed to identify one admission. Conclusion This externally validated algorithm has acceptable predictive ability for identifying patients at high risk of asthma-related crisis events and excluding those not at high risk

Izu-Bonin-Mariana Rear Arc: The Missing Half of the Subduction Factory

4GT) lies in the western part of the Izu fore-arc basin, ~60 km east of the arc-front volcano Aogashima, ~170 km west of the axis of the Izu-Bonin Trench, 1.5 km west of Ocean Drilling Program (ODP) Site 792, and at 1776 meters below sea level (mbsl). It was drilled as a 150 m deep geotechnical test hole for potential future deep drilling (5500 meters below seafloor [mbsf]) at proposed Site IBM-4 using the D/V Chikyu. Core from Site U1436 yielded a rich record of Late Pleistocene explosive volcanism, including distinctive black glassy mafic ash layers that may record large-volume eruptions on the Izu arc front. Because of the importance of this discovery, Site U1436 was drilled in three additional holes (U1436B, U1436C, and U1436D), as part of a contingency operation, in an attempt to get better recovery on the black glassy mafic ash layers and enclosing sediments and to better constrain the thickness of the mafic ash layers. IODP Site U1437 is located in the Izu rear arc, ~330 km west of the axis of the IzuBonin Trench and ~90 km west of the arc-front volcanoes Myojinsho and Myojin Knoll, at 2117 mbsl. The primary scientific objective for Site U1437 was to characterize “the missing half of the subduction factory”; this was because numerous ODP/Integrated Ocean Drilling Program sites had been drilled in the arc to fore-arc region (i.e., ODP Site 782A Leg 126), but this was the first site to be drilled in the rear part of the Izu arc. A complete view of the arc system is needed to understand the formation of oceanic arc crust and its evolution into continental crust. Site U1437 on the rear arc had excellent core recovery in Holes U1437B and U1437D, and we succeeded in hanging the longest casing ever in the history of R/V JOIDES Resolution scientific drilling (1085.6 m) in Hole U1437E and cored to 1806.5 mbsf

A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Funder: Victorian Cancer AgencyFunder: NIHR Manchester Biomedical Research CentreFunder: Cancer Research UKFunder: Cancer Council TasmaniaFunder: Instituto de Salud Carlos IIIFunder: Cancer AustraliaFunder: NIHR Oxford Biomedical Research CentreFunder: Fundación Científica de la Asociación Española Contra el CáncerFunder: Cancer Council South AustraliaFunder: Swedish Cancer SocietyFunder: NIHR Cambridge Biomedical Research CentreFunder: Institut Català de la SalutFunder: Cancer Council VictoriaFunder: Prostate Cancer Foundation of AustraliaFunder: National Institutes of HealthBACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual. FINDINGS: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). INTERPRETATION: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. FUNDING: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Expedition 350 Methods

This chapter of the International Ocean Discovery Program (IODP) Expedition 350 Proceedings volume documents the procedures and tools employed in the various shipboard laboratories of the R/V JOIDES Resolution during Expedition 350. This information applies only to shipboard work described in the Expedition Reports section of this volume. Methods for shore-based analyses of Expedition 350 samples and data will be described in the individual scientific contributions to be published in the open literature or in the Expedition Research Results section of this volume. This section describes procedures and equipment used for drilling, coring, and hole completion; core handling; computation of depth for samples and measurements; and sequence of shipboard analyses. Subsequent sections describe specific laboratory procedures and instruments in more details

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation