Open science in research and innovation for development in Africa

The paper argues that Science Granting Councils (SGC) in their intermediary role between governments and the science community, can act as a collective to achieve efficiencies of scale, stimulating virtual critical masses and intra-African collaboration while creating an African space for open science. It details some tools and processes necessary for supporting open science, as well as the rationale for sharing scientific data, which permits re-use by others as open data. It describes open science platforms or “commons” to provide support to the research process, from information technology infrastructure to high-level analytics and artificial intelligence (AI) procedures.United Kingdom’s Department for International Development (DFID)South Africa’s National Research Foundation (NRF)Swedish International Development Cooperation Agency (Sida

Digital revolution, open science and innovation for development in Sub-Saharan Africa

This policy brief recommends that Science Granting Councils (SGC) through the SGC Initiative (SGCI) intensify the level, scope and ambition of collective action by developing an African open science area, and by seeking support and acquiescence of respective country governments in doing so. It provides background to an open science movement, which includes a digitized ‘commons’ or platform, through collective action by member states in sub-Sharan Africa. The African Technology Policy Studies Network (ATPS) provides platforms for regional and international research and knowledge sharing in order to build Africa’s capabilities in STI policy research, policymaking and implementation for sustainable development.United Kingdom’s Department for International Development (DFID)South Africa’s National Research Foundation (NRF)Swedish International Development Cooperation Agency (Sida

Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology

Amyotrophic Lateral Sclerosis (ALS) causes motor neuron degeneration, with 97% of cases exhibiting TDP-43 proteinopathy. Elucidating pathomechanisms has been hampered by disease heterogeneity and difficulties accessing motor neurons. Human induced pluripotent stem cell-derived motor neurons (iPSMNs) offer a solution; however, studies have typically been limited to underpowered cohorts. Here, we present a comprehensive compendium of 429 iPSMNs from 15 datasets, and 271 post-mortem spinal cord samples. Using reproducible bioinformatic workflows, we identify robust upregulation of p53 signalling in ALS in both iPSMNs and post-mortem spinal cord. p53 activation is greatest with C9orf72 repeat expansions but is weakest with SOD1 and FUS mutations. TDP-43 depletion potentiates p53 activation in both post-mortem neuronal nuclei and cell culture, thereby functionally linking p53 activation with TDP-43 depletion. ALS iPSMNs and post-mortem tissue display enrichment of splicing alterations, somatic mutations, and gene fusions, possibly contributing to the DNA damage response

Rapid systematic review of systematic reviews : what befriending, social support and low intensity psychosocial interventions, delivered remotely, may reduce social isolation and loneliness among older adults and how? [version 2; peer review: 2 approved with reservations]

BACKGROUND: During the COVID-19 pandemic ‘social distancing’ has highlighted the need to minimise loneliness and isolation among older adults (aged 50+). We wanted to know what remotely delivered befriending, social support and low intensity psychosocial interventions may help to alleviate social isolation and loneliness and how they work. METHODS: We followed a systematic ‘review of reviews’ approach. Searches of 11 databases from the fields of health, social care, psychology and social science were undertaken during April 2020. Reviews meeting our PICOS criteria were included if they focussed on the evaluation of remote interventions to reduce levels of social isolation or loneliness in adults aged 50+ and were critically appraised using AMSTAR2. Narrative synthesis was used at a review and study level to develop a typology of intervention types and their effectiveness. Intervention Component Analysis (ICA) and Qualitative Comparative Analysis (QCA) were used at a study level to explore the characteristics of successful interventions. RESULTS: We synthesised evidence from five systematic reviews and 18 primary studies. Remote befriending, social support and low intensity psychosocial interventions took the form of: (i) supported video-communication; (ii) online discussion groups and forums; (iii) telephone befriending; (iv) social networking sites; and (v) multi-tool interventions. The majority of studies utilised the first two approaches, and were generally regarded positively by older adults, although with mixed evidence around effectiveness. Focussing on processes and mechanisms, using ICA and QCA, we found that the interventions that were most successful in improving social support: (i) enabled participants to speak freely and to form close relationships; (ii) ensured participants have shared experiences/characteristics; (iii) included some form of pastoral guidance. CONCLUSIONS: The findings highlight a set of intervention processes that should be incorporated into interventions, although they do not lead us to recommend specific modes of support, due to the heterogeneity of interventions

Haidinger’s brushes elicited at varying degrees of polarization rapidly and easily assesses total macular pigmentation

Macular pigments (MPs), by absorbing potentially toxic short-wavelength (400–500 nm) visible light, provide protection against photo-chemical damage thought to be relevant in the pathogenesis of age-related macular degeneration (AMD). A method of screening for low levels of MPs could be part of a prevention strategy for helping people to delay the onset of AMD. We introduce a new method for assessing MP density that takes advantage of the polarization-dependent absorption of blue light by MPs, which results in the entoptic phenomenon called Haidinger’s brushes (HB). Subjects were asked to identify the direction of rotation of HB when presented with a circular stimulus illuminated with an even intensity of polarized white light in which the electric field vector was rotating either clockwise or anti-clockwise. By reducing the degree of polarization of the stimulus light, a threshold for perceiving HB (degree of polarization threshold) was determined and correlated (r2=0.66) to macular pigment optical density assessed using dual-wavelength fundus autofluoresence. The speed and ease of measurement of degree of polarization threshold makes it well suited for large-scale screening of macular pigmentation

The Effect of DNA-Dependent Protein Kinase on Adeno-Associated Virus Replication

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs

Like mother, like child : investigating perinatal and maternal health stress in post-medieval London.

Post-Medieval London (sixteenth-nineteenth centuries) was a stressful environment for the poor. Overcrowded and squalid housing, physically demanding and risky working conditions, air and water pollution, inadequate diet and exposure to infectious diseases created high levels of morbidity and low life expectancy. All of these factors pressed with particular severity on the lowest members of the social strata, with burgeoning disparities in health between the richest and poorest. Foetal, perinatal and infant skeletal remains provide the most sensitive source of bioarchaeological information regarding past population health and in particular maternal well-being. This chapter examined the evidence for chronic growth and health disruption in 136 foetal, perinatal and infant skeletons from four low-status cemetery samples in post-medieval London. The aim of this study was to consider the impact of poverty on the maternal-infant nexus, through an analysis of evidence of growth disruption and pathological lesions. The results highlight the dire consequences of poverty in London during this period from the very earliest moments of life

Direct access cancer testing in primary care: a systematic review of use and clinical outcomes.

BACKGROUND: Direct access (DA) testing allows GPs to refer patients for investigation without consulting a specialist. The aim is to reduce waiting time for investigations and unnecessary appointments, enabling treatment to begin without delay. AIM: To establish the proportion of patients diagnosed with cancer and other diseases through DA testing, time to diagnosis, and suitability of DA investigations. DESIGN AND SETTING: Systematic review assessing the effectiveness of GP DA testing in adults. METHOD: MEDLINE, Embase, and the Cochrane Library were searched. Where possible, study data were pooled and analysed quantitatively. Where this was not possible, the data are presented narratively. RESULTS: The authors identified 60 papers that met pre-specified inclusion criteria. Most studies were carried out in the UK and were judged to be of poor quality. The authors found no significant difference in the pooled cancer conversion rate between GP DA referrals and patients who first consulted a specialist for any test, except gastroscopy. There were also no significant differences in the proportions of patients receiving any non-cancer diagnosis. Referrals for testing were deemed appropriate in 66.4% of those coming from GPs, and in 80.9% of those from consultants; this difference was not significant. The time from referral to testing was significantly shorter for patients referred for DA tests. Patient and GP satisfaction with DA testing was consistently high. CONCLUSION: GP DA testing performs as well as, and on some measures better than, consultant triaged testing on measures of disease detection, appropriateness of referrals, interval from referral to testing, and patient and GP satisfaction