19 research outputs found

    Visions for the North Sea: The Societal Dilemma Behind Specifying Good Environmental Status.

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    We augment discussions about the Good Environmental Status of the North Sea by developing two extreme visions and assessing their societal benefits. One vision (‘Then’) assumes restoration of benthic functioning; we contend that trawling had already degraded the southern North Sea a century ago. Available information is used to speculate about benthic functioning in a relatively undisturbed southern North Sea. The second vision (‘Now’) draws on recent benthic functioning. The supply of five ecosystem services, supported by benthic functioning, is discussed. ‘Then’ offers confidence in the sustainable supply of diverse services but restoration of past function is uncertain and likely to be paired with costs, notably trawling restraints. ‘Now’ delivers known and valued services but sustained delivery is threatened by, for example, climate change. We do not advocate either vision. Our purpose is to stimulate debate about what society wants, and might receive, from the future southern North Sea

    For children admitted to hospital, what interventions improve medication safety on ward rounds? A systematic review.

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    ObjectiveEvery year, medication errors harm children in hospitals. Ward rounds are a unique opportunity to bring information together and plan management. There is a need to understand what strategies can improve medication safety on ward rounds. We systematically reviewed published interventions to improve prescribing and safety of medicines on ward rounds.DesignSystematic review of randomised controlled trials and observational studies.SettingStudies examining inpatient ward rounds.PatientsChildren and young people aged between 0 and 18 years old.InterventionsAny intervention or combination of interventions implemented that alters how paediatric ward rounds review inpatient medications.Main outcome measurePrimary outcome was improvement in medication safety on paediatric ward rounds. This included reduction in prescribing error rates, healthcare professionals' opinions on prescribing and improvement in documentation on ward rounds.ResultsThree studies were eligible for review. One examined the use of an acrostic, one the use of a checklist, and the other a use of a specific prescribing ward round involving a clinical pharmacist and doctor. None of the papers considered weight-based errors or demonstrated reductions in clinical harm. Reductions in prescribing errors were noted by the different interventions.ConclusionsThere are limited data on interventions to improve medication safety in paediatric ward rounds, with all published data being small scale, either quality improvement or audits, and locally derived/delivered. Good-quality interventional or robust quality improvement studies are required to improve medication safety on ward rounds.Prospero registration numberCRD42022340201

    Improving the experience of obtaining repeat complex paediatric prescriptions in the UK.

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    In the UK, medicines for chronic conditions in children and young people (CYP) are typically initiated within secondary or tertiary care, with responsibility for ongoing supply often then passed to the child's general practitioner (GP) and community pharmacist. The patient should then be reviewed in regular specialist clinics, with two-way communication for any changes in medications or clinical status undertaken between primary and secondary/tertiary care. This arrangement allows long-term medications to be obtained close to home.Although this is what parents expect, the reality is often messy, with families regularly needing to source some medicines from the GPs and others via hospitals or homecare services. In addition, these arrangements are not uniform, they vary across different areas of the UK and depend on individual GP or hospital prescriber acceptance. When neither primary, secondary or tertiary care accepts it is their responsibility to prescribe, or patients are under multiple specialists, families often feel left to navigate this complex and variable supply system themselves. Obtaining a prescription is only the start of the process for families as dispensing from a community pharmacy can also be challenging.In this article, we set out the barriers and potential solutions to this complex issue. We use the term specialist prescribers to include not only paediatricians but all other specialists looking after CYP including child and adolescent psychiatrists, ophthalmologists, dermatologists, surgeons, etc, as well as non-medical prescribers

    Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2

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    Patients lacking PYCR2, a mitochondrial enzyme that synthesizes proline, display postnatal degenerative microcephaly with hypomyelination. Here we report the crystal structure of the PYCR2 apo-enzyme and show that a novel germline p.Gly249Val mutation lies at the dimer interface and lowers its enzymatic activity. We find that knocking out Pycr2 in mice phenocopies the human disorder and depletes PYCR1 levels in neural lineages. In situ quantification of neurotransmitters in the brains of PYCR2 mutant mice and patients revealed a signature of encephalopathy driven by excessive cerebral glycine. Mechanistically, we demonstrate that loss of PYCR2 upregulates SHMT2, which is responsible for glycine synthesis. This hyperglycemia could be partially reversed by SHMT2 knockdown, which rescued the axonal beading and neurite lengths of cultured Pycr2 knockout neurons. Our findings identify the glycine metabolic pathway as a possible intervention point to alleviate the neurological symptoms of PYCR2-mutant patients. Escande-Beillard et al. establish a mouse model of PYCR2 inactivation that phenocopies human neurodegenerative disease (HLD10). Metabolomic and functional analyses in mutant mice and patients reveal that cerebral hyperglycinemia is a driver of the disease, which can be corrected by inhibiting SHMT2
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