Transferring knowledge through peer-reviewed assessment : the creation of a community of practice and the threats to its survival

While it is generally accepted in the learning and teaching literature that assessment is the single biggest influence on how students approach their learning, assessment methods within higher education are generally conservative and inflexible. Constrained by policy and accreditation requirements and the need for the explicit articulation of assessment standards for public accountability purposes, assessment tasks can fail to engage students or reflect the tasks students will face in the world of practice. Innovative assessment design can simultaneously deliver program objectives and active learning through a knowledge transfer process which increases student participation. This social constructivist view highlights that acquiring an understanding of assessment processes, criteria and standards needs active student participation. Within this context, a peer-assessed, weekly, assessment task was introduced in the first “serious” accounting subject offered as part of an undergraduate degree. The positive outcomes of this assessment innovation was that student failure rates declined 15%, tutorial participation increased fourfold, tutorial engagement increased six-fold and there was a 100% approval rating for the retention of the assessment task. In contributing to the core conference theme of “seismic” shifts within higher education, in stark contrast to the positive student response, staff-related issues of assessment conservatism and the necessity of meeting increasing research commitments, threatened the assessment task’s survival. These opposing forces to change have the potential to weaken the ability of higher education assessment arrangements to adequately serve either a new generation of students or the sector's community stakeholders.

Genetics of New-Onset Diabetes after Transplantation

New-onset diabetes after transplantation is a common complication that reduces recipient survival. Research in renal transplant recipients has suggested that pancreatic ß-cell dysfunction, as opposed to insulin resistance, may be the key pathologic process. In this study, clinical and genetic factors associated with new-onset diabetes after transplantation were identified in a white population. A joint analysis approach, with an initial genome-wide association study in a subset of cases followed by de novo genotyping in the complete case cohort, was implemented to identify single-nucleotide polymorphisms (SNPs) associated with the development of new-onset diabetes after transplantation. Clinical variables associated with the development of diabetes after renal transplantation included older recipient age, female sex, and percentage weight gain within 12 months of transplantation. The genome-wide association study identified 26 SNPs associated with new-onset diabetes after transplantation; this association was validated for eight SNPs (rs10484821, rs7533125, rs2861484, rs11580170, rs2020902, rs1836882, rs198372, and rs4394754) by de novo genotyping. These associations remained significant after multivariate adjustment for clinical variables. Seven of these SNPs are associated with genes implicated in ß-cell apoptosis. These results corroborate recent clinical evidence implicating ß-cell dysfunction in the pathophysiology of new-onset diabetes after transplantation and support the pursuit of therapeutic strategies to protect ß cells in the post-transplant period.

Aspectes metodològics i aplicacions de la modelització del temps de supervivència multivariant mitjançant models mixtes

Els estudis de supervivència s'interessen pel temps que passa des de l'inici de l'estudi (diagnòstic de la malaltia, inici del tractament,...) fins que es produeix l'esdeveniment d'interès (mort, curació, millora,...). No obstant això, moltes vegades aquest esdeveniment s'observa més d'una vegada en un mateix individu durant el període de seguiment (dades de supervivència multivariant). En aquest cas, és necessari utilitzar una metodologia diferent a la utilitzada en l'anàlisi de supervivència estàndard. El principal problema que l'estudi d'aquest tipus de dades comporta és que les observacions poden no ser independents. Fins ara, aquest problema s'ha solucionat de dues maneres diferents en funció de la variable dependent. Si aquesta variable segueix una distribució de la família exponencial s'utilitzen els models lineals generalitzats mixtes (GLMM); i si aquesta variable és el temps, variable amb una distribució de probabilitat no pertanyent a aquesta família, s'utilitza l'anàlisi de supervivència multivariant. El que es pretén en aquesta tesis és unificar aquests dos enfocs, és a dir, utilitzar una variable dependent que sigui el temps amb agrupacions d'individus o d'observacions, a partir d'un GLMM, amb la finalitat d'introduir nous mètodes pel tractament d'aquest tipus de dades.

Elaboration et analyse de molécules inhibitrices de protéines de la réparation de l’ADN par recombinaison homologue

Les cellules humaines sont soumises à des stress induisant des cassures double-brin de l’ADN (CDB). Ces CDB sont réparées notamment par la recombinaison homologue, impliquant les protéines RAD51 et RAD52. Une stratégie thérapeutique émergente est de développer des molécules inhibant RAD51 ou RAD52 afin d’accentuer l’instabilité génétique et la mort de la cellule cancéreuse. En effet, dans certains cancers, l’activité de RAD51 est dérégulée promouvant la prolifération tumorale. Il existe plusieurs molécules inhibitrices de RAD51 et nous nous sommes intéressés au DIDS dont le mode d’action n’a pas encore été déterminé. Concernant RAD52, une létalité synthétique a été montrée lorsque celle-ci est inactivée dans des cellules déficientes en BRCA1, BRCA2 ou PALB2, trois gènes mutés dans de nombreux cancers. Récemment, trois types de molécules inhibitrices de RAD52 ont été mis en évidence. Nous avons tout d’abord étudié l’impact du DIDS ainsi que des molécules dérivées afin de comprendre le mécanisme mis en jeu. Nous avons montré que le DIDS, ainsi que ses dérivés inhibent la liaison de RAD51 à l’ADN. Ces molécules empêchent la formation du nucléofilament entrainant une diminution du nombre de foyers RAD51. Nous avons développé une méthode de criblage par fluorescence pour évaluer l’effet d’une banque de 696 molécules sur la capacité de RAD52 à hybrider deux ADNsb. Deux molécules capables d’inhiber la fonction d’hybridation de RAD52 ont été mises au jour. In vivo, elles entrainent une diminution de la survie de cellules déficientes en PALB2. La recherche et le développement de nouveaux inhibiteurs de RAD51 et RAD52 constituent des stratégies thérapeutiques d’avenir.

Survival analysis of time-to-event data in respiratory health research studies

This article provides a review of techniques for the analysis of survival data arising from respiratory health studies. Popular techniques such as the Kaplan–Meier survival plot and the Cox proportional hazards model are presented and illustrated using data from a lung cancer study. Advanced issues are also discussed, including parametric proportional hazards models, accelerated failure time models, time-varying explanatory variables, simultaneous analysis of multiple types of outcome events and the restricted mean survival time, a novel measure of the effect of treatment.

Beta-blocker usage and breast cancer survival: a nested case-control study within a UK clinical practice research datalink cohort.

Background: To investigate the association between post-diagnostic beta-blocker usage and risk of cancer-specific mortality in a large population-based cohort of female breast cancer patients.

Methods: A nested case-control study was conducted within a cohort of breast cancer patients identified from cancer registries in England(using the National Cancer Data repository) and diagnosed between 1998 and 2007. Patients who had a breast cancer-specific death(ascertained from Office of National Statistics death registration data) were each matched to four alive controls by year and age at diagnosis. Prescription data for these patients were available through the Clinical Practice Research Datalink. Conditional logistic regression models were used to investigate the association between breast cancer-specific death and beta-blocker usage.

Results: Post-diagnostic use of beta-blockers was identified in 18.9% of 1435 breast cancer-specific deaths and 19.4% of their 5697 matched controls,indicating little evidence of association between beta-blocker use and breast cancer-specific mortality [odds ratio (OR) = 0.97,95% confidence interval (CI) 0.83, 1.13]. There was also little evidence of an association when analyses were restricted to cardio non-selective beta-blockers (OR = 0.90, 95% CI 0.69, 1.17). Similar results were observed in analyses of drug dosage frequency and duration, and beta-blocker type.

Conclusions: In this large UK population-based cohort of breast cancer patients,there was little evidence of an association between post-diagnostic beta-blocker usage and breast cancer progression. Further studies which include information on tumour receptor status are warranted to determine whether response to beta-blockers varies by tumour subtypes.

Low-dose aspirin and survival in men with prostate cancer: a study using the UK Clinical Practice Research Datalink

Purpose: Aspirin use is associated with reduced risk of, and death from, prostate cancer. Our aim was to determine whether low-dose aspirin use after a prostate cancer diagnosis was associated with reduced prostate cancer-specific mortality.

Methods: A cohort of newly diagnosed prostate cancer patients (1998–2006) was identified in the UK Clinical Practice Research Datalink (confirmed by cancer registry linkage). A nested case–control analysis was conducted using conditional logistic regression to compare aspirin usage in cases (prostate cancer deaths) with up to three controls (matched by age and year of diagnosis).

Results: Post-diagnostic low-dose aspirin use was identified in 52 % of 1,184 prostate cancer-specific deaths and 39 % of 3,531 matched controls (unadjusted OR 1.51, 95 % CI 1.19, 1.90; p < 0.001). After adjustment for confounders including treatment and comorbidities, this association was attenuated (adjusted OR 1.02 95 % CI 0.78, 1.34; p = 0.86). Adjustment for estrogen therapy accounted for the majority of this attenuation. There was also no evidence of dose–response association after adjustments. Compared with no use, patients with 1–11 prescriptions and 12 or more prescriptions had adjusted ORs of 1.07 (95 % CI 0.78, 1.47; p = 0.66) and 0.97 (95 % CI 0.69, 1.37; p = 0.88), respectively. There was no evidence of a protective association between low-dose aspirin use in the year prior to diagnosis and prostate cancer-specific mortality (adjusted OR 1.04 95 % CI 0.89, 1.22; p = 0.60).

Conclusion: We found no evidence of an association between low-dose aspirin use before or after diagnosis and risk of prostate cancer-specific mortality, after potential confounders were accounted for, in UK prostate cancer patients.

Beta-blocker usage and prostate cancer survival:A nested case-control study in the UK Clinical Practice Research Datalink cohort

Background: Recent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case-control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P=0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR=0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

PURPOSE: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.

METHODS: Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.

RESULTS: Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.

CONCLUSIONS: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02)

EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures.

Psychical research and survival,

Mode of access: Internet.

Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial.

PURPOSE: The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact in the context of a prospective randomized trial. PATIENTS AND METHODS: We analyzed the ATM gene in 224 patients treated on the Leukemia Research Fund Chronic Lymphocytic Leukemia 4 (LRF-CLL4) trial with chlorambucil or fludarabine with and without cyclophosphamide. ATM status was analyzed by denaturing high-performance liquid chromatography and was related to treatment response, survival, and the impact of TP53 alterations for the same patient cohort. RESULTS: We identified 36 ATM mutations in 33 tumors, 16 with and 17 without 11q deletion. Mutations were associated with advanced disease stage and involvement of multiple lymphoid sites. Patients with both ATM mutation and 11q deletion showed significantly reduced progression-free survival (median, 7.4 months) compared with those with ATM wild type (28.6 months), 11q deletion alone (17.1 months), or ATM mutation alone (30.8 months), but survival was similar to that in patients with monoallelic (6.7 months) or biallelic (3.4 months) TP53 alterations. This effect was independent of treatment, immunoglobulin heavy chain variable gene (IGHV) status, age, sex, or disease stage. Overall survival for patients with biallelic ATM alterations was also significantly reduced compared with those with ATM wild type or ATM mutation alone (median, 42.2 v 85.5 v 77.6 months, respectively). CONCLUSION: The combination of 11q deletion and ATM mutation in CLL is associated with significantly shorter progression-free and overall survival following first-line treatment with alkylating agents and purine analogs. Assessment of ATM mutation status in patients with 11q deletion may influence the choice of subsequent therapy.