Ensuring travel broadens minds: a suitable case for Learning Design?

O’Sullivan (2018, p. 283) advocates ‘an ability to continue to learn, both from your own experience and from the good practice of others’ as a strategy for professional development in cultural organisations, using a case study of international exchange visits. Yet in spite of their popularity, there is little systematic evaluation of such exchanges. The lack of an evidence base for improving practice in cultural and educational exchange visits threatens their continued justification in a resource-constrained environment. It threatens to leave barriers to participation intact through lack of analysis (Gastinger, 2011; O’Sullivan and Flecknoe, 2000), and perpetuates the danger of transferring inappropriate educational paradigms and cultural ideologies through unexamined practices (Cramp, 2016: Fallon and Paquette, 2015; Maranzan et al, 2013; Martin and Griffiths, 2012). On the other hand, evidence-based improvements in the effectiveness of cultural and educational exchanges would strengthen the case for widening participation (MacInnes et al, 2019) and increase their value to international educational development (British Council, 2018). As a learning tool, international exchange visits should be amenable to the same quality enhancement processes used for other educational materials. The UK Open University has embraced Learning Design (Cross, et al., 2012) as a methodology for the design and continuous improvement of its courses. Learning Design theory analyses courses into generic activities centred on learner needs and experience. Designs can be tested, reused and refined as appropriate in the light of evidence from learning analytics (Rientes and Toetenel, 2016; O’Sullivan and O’Sullivan, 2018). Drawing on literature and case studies, we propose that applying the principles of Learning Design to planning exchange visits will help prevent some of the identified practical and ideological problems. Furthermore, we argue that incorporating elements of distance learning around the exchange visit will improve and enrich the value of this kind of professional development

Lessons from 'MOOCs for credit’ -- turning non-formal learning into formal credit

The unprecedented growth in learning material freely available on the web appears to offer enormous opportunities to learners and educators all over the world, especially in countries keen to accelerate educational development but hampered by lack of resources (Garrido and Koepke, 2016; Kursun, 2016; Laurillard and Kennedy, 2017; Sclater, 2016). Imagining the University of the future in Africa demands consideration of the role to be played by such material in curriculum and delivery. However, integrating Massive Open Online Courses (MOOCs) and other Open Educational Resources (OERs) into, or alongside, formal accredited learning has its challenges. MOOCs often draw on educational paradigms which may be inconsistent with formal qualifications (Anders, 2015; Bradshaw, et al., 2017); OERs require discovery, evaluation and adaptation (Petrides et al., 2010); and incorporating OERs and MOOCs into credit-bearing qualifications can create tension with existing administrative systems (O’Sullivan, 2018) and external stakeholders (Daniel, in Latcham, 2012; Universities UK, 2013). This paper reflects on how the UK Open University’s MOOCs for Credit initiative has addressed these challenges in offering the UK’s first explicit route to formal academic credit from non-formal study in FutureLearn MOOCs (Weale, 2016). Taking into account processes of planning, production, marketing, administration and delivery, the paper discusses advantages and disadvantages of the MOOCs for Credit model compared to alternatives, and identifies implications for practice. The heady initial promise of MOOCs and OERs as profound disruptors of global Higher Education may well have been unrealistic, but, consciously adapted and managed, such resources still have substantial potential in the creation of ‘new higher education credentials, business models, and approaches to delivering degrees’ (Gallagher, 2017) in Africa and elsewhere

Gemini/GMOS Imaging of Globular Cluster Systems in Five Early-type Galaxies

This paper presents deep high quality photometry of globular cluster (GC) systems belonging to five early-type galaxies covering a range of mass and environment. Photometric data were obtained with the Gemini North and Gemini South telescopes in the filter passbands g', r', and i'. The combination of these filters with good seeing conditions allows an excellent separation between GC candidates and unresolved field objects. Bimodal GC colour distributions are found in all five galaxies. Most of the GC systems appear bimodal even in the (g' -r') vs (r' -i') plane. A population of resolved/marginally resolved GC and Ultra Compact Dwarf candidates was found in all the galaxies. A search for the so-called "blue tilt" in the colour-magnitude diagrams reveals that NGC 4649 clearly shows that phenomenon although no conclusive evidence was found for the other galaxies in the sample. This "blue tilt" translates into a mass-metallicity relation given by Z \propto M^0.28\pm0.03 . This dependence was found using a new empirical (g' -i') vs [Z/H] relation which relies on an homogeneous sample of GC colours and metallicities. This paper also explores the radial trends in both colour and surface density for the blue (metal-poor) and red (metal-rich) GC subpopulations. As usual, the red GCs show a steeper radial distribution than the blue ones. Evidence of galactocentric colour gradients is found in some of the GC systems, being more significant for the two S0 galaxies in the sample. Red GC subpopulations show similar colours and gradients to the galaxy halo stars in their inner region. A GC mean colour-galaxy luminosity relation, consistent with [Z/H] \propto L_B ^0.26\pm0.08, is present for the red GCs. An estimate of the total GC populations and specific frequency SN values is presented for NGC 3115, NGC 3379, NGC 3923 and NGC 4649.Comment: 23 pages, 13 figures and 9 tables. Tables A1 and A2 will be published in full online only. Accepted for publication in MNRA

The psychological and genetic factors of the addictive behaviors (PGA) study

Objectives: Most of the addiction studies focus on very specific aspects of addictions, often with contradictory results, and integrated studies are quite rare. Experimental studies comparing underlying mechanisms of addictions and analyzing data from an integrative psychological and genetic perspective are almost nonexistent. The aim of the present paper is to describe the research protocol of the Psychological and Genetic Factors of Addictive Behaviors (PGA) study, which applies an integrative approach to understanding the acquisition, development, and maintenance of addictive behaviors. Methods: A wide-spectrum national study was carried out. Data were collected from 3,003 adolescents. Addictions to both psychoactive substances and behaviors were thoroughly assessed via psychometrically robust scales, which also included assessment related to a wide range of related psychological dimensions. Additionally, a DNA sample was also collected from participants. Results: The paper presents the detailed methodology of the PGA study. Data collection procedures, instrumentation, and the analytical approach used to attain the research objectives are described. Conclusions: Future plans, along with potential contributions of the PGA study, are also discussed. It is envisaged that the study will provide a unique opportunity to test possible mechanisms and causal pathways mediating the associations of genetic factors, psychological characteristics, and addictions

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Breast cancer polygenic risk score and contralateral breast cancer risk

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies