Interdisciplinary Insights on Open Source

The term “open source” is widely applied to describe some software development methodologies. This paper does not provide a judgment on the open source approach, but exposes the fact that simply stating that a project is open source does not provide a precise description of the approach used to support the project. By taking a multi- disciplinary point of view, we propose a collection of characteristics that are common, as well as some that vary among open source projects. The set of open source characteristics we found can be used as a tick-list both for analysing and for setting up open source projects. Our tick-list also provides a starting point for understanding the many meanings of the term open source

Using multiple representations to enhance understanding of molecular structure: a blended learning activity

One of the challenges of teaching an introductory chemistry course is to balance the requirement of covering a prescribed set of concepts and skills with providing opportunities for students to spend time with, and apply, a single concept. In this chemistry course, students encounter an array of molecular representations including line drawings, condensed structures, ball and sticks and three dimensional space filled molecules. They must quickly become fluent in translating between these representations and in a lecture setting are likely to acquire misconceptions. To address these issues, a blended learning workshop was developed to present active learning opportunities for students in the application and extension of their understanding of molecular structure. An integrative approach was adopted by using the context of fats in the diet to demonstrate the relevance of the chemistry concepts to the student’s daily lives. This involved the adaptation of a successful ChemConnections initiative (http://mc2.cchem.berkeley.edu/). Students were guided through inquiry activities involving online resources (Jmol), hands-on molecular model kits (Molymod) and a graphics application on individual tablet PCs where they drew molecular structures. Student learning gains and metacognitive processing were measured via three strategies incorporating the unique facilities of the teaching space. The availability of individual tablet computers enabled collection of student representations of a line structure prior to commencement of the workshop. As part of the assessment of the exercise, students were invited to submit brief reflections (via personal blogs managed through Blackboard). Students identified multiple themes regarding the aspect of the workshop that had impacted on their learning (working as groups, molecular models and the high technology facilities). Gains in conceptual understanding were explored through two post-workshop assessment tasks. A related problem was placed in PASS (Peer Assisted Study Sessions) where students worked in peer groups without instructor input, and a short answer question was included in the summative exam for the course. Students reported high confidence levels in their ability to recognise organic structures as a result of the activities encountered during the workshop. A mixed methods approach was adopted for the evaluation of the learning experience including pre- and post-tests conducted at each workshop, focus group interviews and feedback from students (postworkshop reflections, a problem set in a pseudotutorial environment and summative exam question). Data gathered has been evaluated through quantitative and qualitative analysis (SPSS and NVivo)

Student behavioural engagement in self-paced online learning

It remains a challenge in online settings to engage students as independent learners without teacher presence. This has led to increasing attention investigating the factors influencing student engagement in this context. As part of a PhD study, this paper investigates students' behavioural engagement with online learning modules without teacher supervision or peer support. The study examines three key constructs of behavioural engagement: student engagement with the task, effort level the student applies to taskcompletion and finally, following instructions. First, the findings suggest that student engagement was high in ‘video' and 'feedback' sections as compared to ‘simulation’ activities. Second, students invested high effort in task-completion when the learning modules were delivered with instructional guidance. Finally, non-visual learners exhibit more difficulty following instructions in unsupported online settings. The results of this study will contribute to the burgeoning research field promoting the development of online modules that encourage participation of diverse learners

Factors affecting student engagement in self-directed online learning module

Background In education delivered through an online self-regulated learning mode, students’ ability to learn and engage varies with different factors. Considering the absence of teacher supervision and opportunities to provide direct feedback, students may lack opportunities to control and interact with a learning environment, which might lead them to less engagement with learning activities (Krause & Coates, 2008; Tuckman, 2007). Aims The objective of this study is to investigate how students engage with and apply their effort to complete the tasks in the module. The study objective also includes the cognitive engagement to understand the concepts and how engagement has been demonstrated in the activities. Further investigated is the student enthusiasm towards task completion and student choice to engage with different learning tools like simulations and videos. Design and methods This study investigates student engagement with two online learning modules. These modules address the concepts of introductory science topics 'Phase Changes' and 'Heat'. The modules are comprised of simulation models, videos with textual information and pictures. The learning models have been developed for self-paced independent study incorporating the extensive use of the Predict, Observe and Explain (POE) pedagogical strategy (White & Gunstone, 1992). The modules are designed to occupy students for about 50-60 minutes. The total number of participations is 30 from the first year science students of an Australian university. The researchers used observational notes, recorded video, and interviews to collect and analysis the data. At the beginning, the students were given a brief introduction and then left to work independently with the online learning module. The researcher observed the student’s computer screen activity in an adjacent room using VNC software. The researcher then monitored the student progress of the investigation and noting points for discussion. Echo360 software ran in the students’ computer to record the student activity on the screen. Once students finished the activity, the researcher conducted a stimulated recall interview using the recorded student activity as the stimulus (O'Brien, 1993). Results The study revealed that student engagement with the video activities is high, compare to the simulation models, due to less cognitive load required in the learning process. Several students demanded systematic instructions and guidance for improved engagement with the simulations. However, the simulation with the tactile perception attracted greater student engagement. Comparatively, student engagement was less when the task required explaining their understanding in response questions designed to check a concept. Nevertheless, the feedback sections produced high engagement as the students wanted to clarify their understanding during the learning process. Conclusions This study brings forward the issues concerning the student engagement in self-directed online learning with possible suggestions. The findings will contribute to change the practice of the teachers and educators in developing the online module. References O'Brien, J. (1993). Action research through stimulated recall. Research in Science Education, 23(1), 214-221. doi: 10.1007/BF02357063 Krause, K. L., & Coates, H. (2008). Students’ engagement in first year university. Assessment & Evaluation in Higher Education, 33(5), 493-505. Tuckman, B. W. (2007). The effect of motivational scaffolding on procrastinators’ distance learning outcomes. Computers & Education, 49(2), 414-422. White, R., & Gunstone, R. (1992). Probing Understanding. Great Britain: Falmer Press

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials