Marine heatwaves and cold spells in the Northeast Atlantic: what should the UK be prepared for?

Up to now, the UK has avoided major marine heatwaves (MHWs) that cause severe damage to marine ecosystems and the blue economy. However, an unprecedented in its intensity, though short-lived, MHW occurred in UK waters in June 2023. This event sounded an alarm bell, highlighting gaps in our understanding of MHW characteristics and their potential future impacts in the UK. Here, we use a combination of remote sensing data and model output to characterise MHWs and Marine Cold Spells (MCSs) around the UK and the wider North Atlantic, and to assess the potential for concurrent biogeochemical extreme events. Results indicate that across the wider North Atlantic, the UK is not a hot spot for MHWs or MCSs but, regionally, the southern North Sea experiences the most activity. This is also the location of extreme chlorophyll-a concentrations, here termed blue waves (low chlorophyll-a) and green waves (high chlorophyll-a). However, there is not a very pronounced relationship between temperature and chlorophyll-a extremes, which may be impacted by the exact location, drivers and season of occurrence. In contrast, the southern North Sea and English Channel may experience a MHW and low near-bottom oxygen compound events year-round, which, due to the combination of thermal stress and reduced oxygen availability, may negatively impact benthic marine ecosystems. While MHWs in UK waters do not appear to be as long-lasting or intense as other well-documented events around the world, they are projected to increase. Thus, the UK has a unique opportunity to learn from other nations and so develop robust and comprehensive policies to increase preparedness and response capability for future extreme events

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA)

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin‐dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes

PFS24 as a prognostic milestone in patients with newly diagnosed primary CNS lymphoma

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has significantly improved overall survival (OS) in primary central nervous system lymphoma (PCNSL). However, early identification of long-term survivors remains a challenge. Progression-free survival at 24 months (PFS24) has emerged as a key prognostic marker in diffuse large B-cell lymphoma, but its relevance in PCNSL is still unclear. In this retrospective multicenter study, we analyzed data from 146 newly diagnosed, transplant-eligible PCNSL patients treated with MATRix-like regimens across 14 hospitals. With a median follow-up of 48 months, the 2-year PFS and OS rates were 50.4% and 65.6%, respectively. Of the 139 patients evaluable for PFS24-analysis, 51.1% reached PFS24, with a subsequent 5-year OS of 96.7%. Of note, the annual hazard rate for progression and death decreased to under 5% after 24 months, remaining stable thereafter. The patients who failed to reach PFS24 had a median OS of only 6.0 months. Key predictors of PFS failure included impaired Karnofsky performance status and treatment dose-reduction. In conclusion, PFS24 was identified as an important prognostic marker in PCNSL. Patients who achieve PFS24 have a favorable prognosis, whereas those who do not face poor outcomes and require innovative treatment approaches. This insight could aid in risk stratification and support the use of PFS24 as a surrogate endpoint in clinical trials

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Point-of-care testing in paediatric settings in the UK and Ireland: A cross-sectional study

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

Gulf Stream transport and pathway variability: the importance of air-sea fluxes

Understanding the various mechanisms that control path and transport variability of the Gulf Stream (GS) is important due to its major role in the global redistri- bution of heat. This work provides evidence that localised surface heat fluxes can induce changes in the path and strength of the GS.Interannual path and transport variability of the GS are calculated here using different methods in a range of observational products, which are compared to high resolution (eddy-resolving) ocean model output. It is shown that changes in the baroclinic transport, i.e. the density-driven component, are crucial in controlling total GS transport variability. Furthermore, observational and model evidence was found that intense air-sea fluxes during severe winters alters the cross-stream density structure and in turn the GS transport compared to the previous year. The investigation found that these years were also associated with deeper mixed layers, strengthened meridional temperature gradients (to the north and south of the GS core) and an intensified westward component of the southern recirculation.Lagrangian analysis is performed to examine GS pathway variability. Distinctive characteristics of the recirculating and Subpolar Gyre (SPG)-bound pathways are revealed. In particular, a more direct, faster, subsurface pathway to the SPG is revealed than has been found previously. By demonstrating that this pathway had increased throughput to this region during the 1990s, it is possible for the first time to reconcile the 1990s SPG warming with a Lagrangian approach. The influx of warm water during this decade is related to air-sea fluxes associated with the North Atlantic Oscillation (NAO). Additionally, near-surface pathways are significantly correlated to the wind stress curl over the STG.<br/

The use of formative assessment to teach writing skills to English First Additional Language learners

Many South African parents prefer English as the language of instruction and associate it with greater socio-economic success for their children. Constructive writing may be experienced as challenging for learners whose home language is not English. Studies have highlighted poor reading skills in South Africa, and reading and writing are overlapping constructs. I aimed to explore how teachers use formative assessment in teaching writing skills to English First Additional Language Grade 4-6 learners. I applied Walqui’s (2006) model of scaffolding which is based on Vygotsky’s Sociocultural Theory. The theory combines the interactive and collaborative nature of learning support. I applied a qualitative research approach, using a phenomenological strategy. Nine teachers from three Setswana home language primary schools were purposively sampled, three English teachers from each school were selected. I used semi-structured interviews, classroom observations and document analyses to collect data over six weeks and analysed it using qualitative content analysis. The main findings revealed that teachers were unable to use formative assessment effectively in their teaching of writing due to factors such as learners’ poor proficiency in English, lack of parental support, overcrowded classrooms, limited time, an inadequate supply of teaching and learning resources, and a lack of intervention strategies for progressed learners. Though these findings cannot be generalised to a greater population because of sample size, various strategies for teaching writing were revealed, which can be useful for teachers. The dissertation is concluded by giving some suggestions for future research. Key Terms: Assessment; Formative assessment; Teaching and learning; Writing skills; First Additional Language; English First Additional Language; Language of Learning and Teaching.Dissertation (MEd)--University of Pretoria, 2021.Science, Mathematics and Technology EducationMEdUnrestricte