Long-range Angular Correlations On The Near And Away Side In P-pb Collisions At √snn=5.02 Tev

7191/Mar294

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)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Prevalence and correlates of prescription drug diversion and misuse among people living with HIV in the eThekwini district, KwaZulu-Natal, South Africa.

BackgroundPrescription drug diversion, and misuse has increased over the past decade and is notably in high-income-countries and significantly contributes to the opioid epidemic. People living with HIV (PLWH) are particularly vulnerable to prescription drug diversion, and misuse as most experience chronic pain, mental health problems and HIV-related illnesses. The researchers investigated the prevalence and correlates of prescription drug diversion, and misuse among PLWH in the eThekwini district, KwaZulu-Natal.MethodsA cross-sectional study was conducted among 392 PLWH, conveniently recruited from the public healthcare facilities located in rural, semi-urban and urban areas of the eThekwini district. Participants answered questions about their background, prescription medications, substance use, and prescription drug diversion, and misuse. Descriptive analysis was performed to estimate the prevalence of prescription drug diversion, and misuse. Multivariable logistic regression was used to identify predictors of prescription drug diversion, and misuse.FindingsOverall, 13% of the participants reported lifetime prescription drug diversion. The most common type of diversion was using prescription medication not prescribed by a healthcare provider (11%), followed by sharing of prescription medication (9%) and buying prescription medication without a medical script (5%). Twenty-three per cent of the participants reported prescription drug misuse in the past 90 days, with using prescription medication without a healthcare providers' guidance (9%) and not following the scheduled time periods (8%) being the most common reported types of misuse. Self-medicating was identified as a risk factor for prescription drug misuse. There was no association between ART adherence and prescription drug diversion, and misuse.ConclusionThe study findings contribute to improving the limited data available on prescription drug diversion, and misuse among PLWH in South Africa. The prevalence underscores a need for urgent interventions when prescribing medications with potential risks. Addressing the risk of self-medicating is imperative for HIV care outcomes and to avert death

An enhanced interface analysis method for engineering change management

NoThe complexity of automotive systems has increased dramatically, driven by the requirement to address environmental and safety concerns and the pressure to offer higher level consumer technologies. This places a great challenge on product development organizations to manage the multidisciplinary systems integration in a reliable and robust manner. Engineering changes, which are integral part of the iterative automotive product development process, need to be managed in a way that efficiently addresses the integration requirements of complex multidisciplinary systems. The aim of this paper is to present a structured approach for engineering change management which is based on an enhanced interface analysis method which aims to identify comprehensively the system integration functional requirements as the basis for both engineering change prediction and support of robust engineering change design. The framework will be illustrated with an industrial case study on the development of an electric vehicle powertrain. The effectiveness of the proposed approach will be discussed in contrast with other methods for engineering change management

Transition from Process- to Product-Level Perspective for Business Software

Part 2: Short PapersInternational audienceWhen there are insufficient inputs for a product-level approach to requirements elicitation, a process-level perspective is an alternative way for achieving the intended base requirements. We define a V+V process approach that supports the creation of the intended requirements, beginning in a process level perspective and evolving to a product-level perspective trough successive models derivation with the purpose of creating context for the implementation teams. The requirements are expressed through models, namely logical architectural models and stereotyped sequence diagrams. Those models alongside with the entire approach are validated using the architecture validation method ARID