Scn1b deletion in adult mice results in seizures and SUDEP

Pathogenic lossâ ofâ function variants in SCN1B are linked to Dravet syndrome (DS). Previous work suggested that neuronal pathfinding defects underlie epileptogenesis and SUDEP in the Scn1b null mouse model of DS. We tested this hypothesis by inducing Scn1b deletion in adult mice that had developed normally. Epilepsy and SUDEP, which occur by postnatal day 21 in Scn1b null animals, were observed within 20 days of induced Scn1b deletion in adult mice, suggesting that epileptogenesis in SCN1Bâ DS does not result from defective brain development. Thus, the developmental brain defects observed previously in Scn1b null mice may model other coâ morbidities of DS.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149575/1/acn3785.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149575/2/acn3785_am.pd

Bright spots as climate-smart marine spatial planning tools for conservation and blue growth

Marine spatial planning that addresses ocean climate-driven change (‘climate-smart MSP’) is a global aspiration to support economic growth, food security and ecosystem sustainability. Ocean climate change (‘CC’) modelling may become a key decision-support tool for MSP, but traditional modelling analysis and communication challenges prevent their broad uptake. We employed MSP-specific ocean climate modelling analyses to inform a real-life MSP process; addressing how nature conservation and fisheries could be adapted to CC. We found that the currently planned distribution of these activities may become unsustainable during the policy's implementation due to CC, leading to a shortfall in its sustainability and blue growth targets. Significant, climate-driven ecosystem-level shifts in ocean components underpinning designated sites and fishing activity were estimated, reflecting different magnitudes of shifts in benthic versus pelagic, and inshore versus offshore habitats. Supporting adaptation, we then identified: CC refugia (areas where the ecosystem remains within the boundaries of its present state); CC hotspots (where climate drives the ecosystem towards a new state, inconsistent with each sectors’ present use distribution); and for the first time, identified bright spots (areas where oceanographic processes drive range expansion opportunities that may support sustainable growth in the medium term). We thus create the means to: identify where sector-relevant ecosystem change is attributable to CC; incorporate resilient delivery of conservation and sustainable ecosystem management aims into MSP; and to harness opportunities for blue growth where they exist. Capturing CC bright spots alongside refugia within protected areas may present important opportunities to meet sustainability targets while helping support the fishing sector in a changing climate. By capitalizing on the natural distribution of climate resilience within ocean ecosystems, such climate-adaptive spatial management strategies could be seen as nature-based solutions to limit the impact of CC on ocean ecosystems and dependent blue economy sectors, paving the way for climate-smart MSP

Bright spots as climate‐smart marine spatial planning tools for conservation and blue growth

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'Ain't it a Ripping Night': Alcoholism and the Legacies of Empire in Salman Rushdie's Midnight's Children.

In the era of decolonisation that followed the Second World War, various authors sought to engage with India and the Empire’s past anew throughout their novels, identifying medicine and illness as key parts of Imperial authority and colonial experience. Salman Rushdie’s approach to the Raj in Midnight’s Children (1981) focused on the broad sweep of colonial life, juxtaposing the political and the personal. This article argues that Rushdie explores the history of colonial India by employing alcohol and alcoholism as lenses through which to explore the cultural, political and medical legacies of Empire. Through analysis of Midnight’s Children as well as a range of medical sources related to alcohol and inebriation, it will illustrate how drinking is central to Rushdie’s approach to secular and religious identities in newly independent India, as well as a means of satirising and undermining the supposed benefit that Empire presented to India and Indians

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

BACKGROUND: Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. METHODS: A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. RESULTS: Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). CONCLUSIONS: This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine