Towards the devolution of lifewide learning awards through verifiable digital badges

Lifewide learning has grown in importance amongst UK universities, with many now offering award programmes to both encourage students to take part in extra- and co-curricular activities and to recognise their efforts in these areas. However, the typical requirement to align these awards with the existing academic year means that the submission and assessment of the awards occur at one of the most demanding times of the year for both students and staff. This paper suggests that a model for lifewide learning awards where the assessment activities are devolved to trusted third-parties would help to reduce the burden on students and staff. The idea of Open Badges, a standard for creating and sharing secure, verifiable digital credentials and evidence, is proposed and discussed using a case study as a means to support a devolved approach to lifewide learning awards

Towards the devolution of lifewide learning awards through verifiable digital badges

Lifewide learning has grown in importance amongst UK universities, with many now offering award programmes to both encourage students to take part in extra- and co-curricular activities and to recognise their efforts in these areas. However, the typical requirement to align these awards with the existing academic year means that the submission and assessment of the awards occur at one of the most demanding times of the year for both students and staff. This paper suggests that a model for lifewide learning awards where the assessment activities are devolved to trusted third-parties would help to reduce the burden on students and staff. The idea of Open Badges, a standard for creating and sharing secure, verifiable digital credentials and evidence, is proposed and discussed using a case study as a means to support a devolved approach to lifewide learning awards

Associations between early term and late/post term infants and development of epilepsy:A cohort study

Background While life-long impacts exist for infants born one or two weeks early little evidence exists for those infants born after their due date. However interventions could be used to expedite birth if the risks of continuing the pregnancy are higher than intervening. It is known that the risk of epilepsy in childhood is higher in infants exposed to perinatal compromise and therefore may be useful as a proxy for intrapartum compromise. The aim of this work is to quantify the likelihood of children developing epilepsy based on their gestational age at birth (37–39 weeks or ≥41 weeks). Methods The work is based on term infants born in Sweden between 1983 and 1993 (n = 1,030,168), linked to data on disability pension, child mortality and in-patient epilepsy care. The reference group was defined as infants born at 39 or 40 completed weeks of gestation; compared with infants born at early term (37/38 weeks) or late/post term (41 weeks or more). Primary outcome was defined a-priori as a diagnosis of epilepsy before 20 years of age. Secondary outcomes were childhood mortality (before five years of age), and registered for disability pension before 20 years of age. Logistic regression models were used to assess any association of the outcomes with gestational age at birth. Findings In the unadjusted results, infants born 7 or more days after their due date had higher risks of epilepsy and disability pension than the reference group, but similar risks of child death. Early term infants showed higher risks of epilepsy, disability pension and child death. After adjustment for confounders, there remained a higher risk of epilepsy for both early term (OR 1·19 (1·11–1·29)) and late/post term infants (OR 1·13 (1·06–1·22)). Interpretation Infants born at 37/38 week or 41 weeks and above, when compared to those born at 39 or 40 weeks gestation, have an increased risk of developing epilepsy. This data could be useful in helping women and care givers make decisions with regard to the timing of induction of labour

Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report.

Based on the profile of genetic alterations occurring in tumor samples from selected diffuse large B-cell lymphoma (DLBCL) patients, 2 recent whole-exome sequencing studies proposed partially overlapping classification systems. Using clustering techniques applied to targeted sequencing data derived from a large unselected population-based patient cohort with full clinical follow-up (n = 928), we investigated whether molecular subtypes can be robustly identified using methods potentially applicable in routine clinical practice. DNA extracted from DLBCL tumors diagnosed in patients residing in a catchment population of ∼4 million (14 centers) were sequenced with a targeted 293-gene hematological-malignancy panel. Bernoulli mixture-model clustering was applied and the resulting subtypes analyzed in relation to their clinical characteristics and outcomes. Five molecular subtypes were resolved, termed MYD88, BCL2, SOCS1/SGK1, TET2/SGK1, and NOTCH2, along with an unclassified group. The subtypes characterized by genetic alterations of BCL2, NOTCH2, and MYD88 recapitulated recent studies showing good, intermediate, and poor prognosis, respectively. The SOCS1/SGK1 subtype showed biological overlap with primary mediastinal B-cell lymphoma and conferred excellent prognosis. Although not identified as a distinct cluster, NOTCH1 mutation was associated with poor prognosis. The impact of TP53 mutation varied with genomic subtypes, conferring no effect in the NOTCH2 subtype and poor prognosis in the MYD88 subtype. Our findings confirm the existence of molecular subtypes of DLBCL, providing evidence that genomic tests have prognostic significance in non-selected DLBCL patients. The identification of both good and poor risk subtypes in patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) clearly show the clinical value of the approach, confirming the need for a consensus classification.Bloodwise (grant number 15037) funded the majority of this study. Genetic sequencing was funded by 14M Genomics, a start-up company that ceased trading February 2016. DJH was funded by a clinician scientist fellowship from the MRC and receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. Some of the analysis in this study was performed on the “Viking” high performance computing cluster at the University of York.1

Regulation of transcription termination in the nematode Caenorhabditis elegans

The current predicted mechanisms that describe RNA polymerase II (pol II) transcription termination downstream of protein expressing genes fail to adequately explain, how premature termination is prevented in eukaryotes that possess operon-like structures. Here we address this issue by analysing transcription termination at the end of single protein expressing genes and genes located within operons in the nematode Caenorhabditis elegans. By using a combination of RT-PCR and ChIP analysis we found that pol II generally transcribes up to 1 kb past the poly(A) sites into the 3′ flanking regions of the nematode genes before it terminates. We also show that pol II does not terminate after transcription of internal poly(A) sites in operons. We provide experimental evidence that five randomly chosen C. elegans operons are transcribed as polycistronic pre-mRNAs. Furthermore, we show that cis-splicing of the first intron located in downstream positioned genes in these polycistronic pre-mRNAs is critical for their expression and may play a role in preventing premature pol II transcription termination

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Molecular subclusters of follicular lymphoma: a report from the UK's Haematological Malignancy Research Network

Follicular lymphoma (FL) is morphologically and clinically diverse, with mutations in epigenetic regulators alongside t(14;18) identified as disease-initiating events. Identification of additional mutational entities confirms this cancer’s heterogeneity, but whether mutational data can be resolved into mechanistically distinct subsets remains an open question. Targeted sequencing was applied to an unselected population-based FL cohort (n = 548) with full clinical follow-up (n = 538), which included 96 diffuse large B-cell lymphoma (DLBCL) transformations. We investigated whether molecular subclusters of FL can be identified and whether mutational data provide predictive information relating to transformation. DNA extracted from FL samples was sequenced with a 293-gene panel representing genes frequently mutated in DLBCL and FL. Three clusters were resolved using mutational data alone, independent of translocation status: FL_aSHM, with high burden of aberrant somatic hypermutation (aSHM) targets; FL_STAT6, with high STAT6 & CREBBP mutation and low aSHM; and FL_Com, with the absence of features of other subtypes and enriched KMT2D mutation. Analysis of mutation signatures demonstrated differential enrichment of predicted mutation signatures between subgroups and a dominant preference in the FL_aSHM subgroup for G(C>T)T and G(C>T)C transitions consistent with previously defined aSHM-like patterns. Of transformed cases with paired samples, 17 of 26 had evidence of branching evolution. Poorer overall survival (OS) in the aSHM group (P = .04) was associated with older age; however, overall tumor genetics provided limited information to predict individual patient risk. Our approach identifies 3 molecular subclusters of FL linked to differences in underlying mechanistic pathways. These clusters, which may be further resolved by the inclusion of translocation status and wider mutation profiles, have implications for understanding pathogenesis as well as improving treatment strategies in the future

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening