Gordon Valentine Manley and his contribution to the study of climate change: a review of his life and work

British climatologist and geographer, Gordon Manley (1902–1980), is perhaps best known for his pioneering work on climate variability in the UK, for establishing the Central England Temperature series and, for his pivotal role in demonstrating the powerful relationship between climate, weather, and culture in post-World War II Britain. Yet Manley made many contributions, both professional and popular, to climate change debates in the twentieth century, where climate change is broadly understood to be changes over a range of temporal and spatial scales rather than anthropogenic warming per se. This review first establishes how Manley's work, including that on snow and ice, was influenced by key figures in debates over climatic amelioration around the North Atlantic between 1920s and 1950s. His research exploring historical climate variability in the UK using documentary sources is then discussed. His perspectives on the relationship between climate changes and cultural history are reviewed, paying particular attention to his interpretation of this relationship as it played out in the UK. Throughout, the review aims to show Manley to be a fieldworker and an empiricist and reveals how he remained committed to rigorous scientific investigation despite changing trends within his academic discipline

Third Party Reports influence parents’ perceptions of coaching ability: Implications for youth sport coaches.

According to Olson, Roese, and Zanna’s (1996) Model of Expectancy Processes, information conveyed by others can determine our expectancies of people. Furthermore, Third Party Reports (TPRs) such as reputation may influence athletes’ initial expectancies of coaches (e.g., Manley et al., 2008; 2010; Thelwell et al., 2013). Parents are believed to play a fundamental role in the development of coach-athlete relationships (e.g., Jowett & Katchis, 2005) and, in turn, athletic achievement in youth sport (Gould et al., 2008). However, person perception research has not yet examined the impact of cues such as TPRs on the initial impressions and expectancies that parents form of youth sport coaches. The current study addresses this gap in the literature. Athletes’ parents viewed a hypothetical online report describing the appointment of a new coach at a local sports club. The report included a “comments” section, which consisted of “tweets” posted by the newly-appointed coach’s former athletes. Four experimental conditions were created by manipulating the coach’s level of warmth and competence (i.e., high vs. low) as reported through the “comments/tweets” (i.e., TPRs). After reading the online report, participants provided ratings of the coach’s ability using the Coaching Competency Questionnaire (Myers et al., 2006). Participants are currently being recruited via gatekeepers at sports clubs/organisations, as well as through social media. However, based on an initial sample (n = 83), Kruskal-Wallis tests typically revealed that high-warmth/high-competence TPRs resulted in highest evaluations of overall coaching ability, while TPRs low in both warmth and competence received poorest ratings. Interestingly, perceptions of Character-building Competence were highest for high-warmth/low-competence TPRs. These preliminary findings reveal that TPRs can influence parents’ perceptions of coaching proficiency, but that parents may value warmth over competence when assessing a coach’s ability to develop more holistic qualities in youth sport athletes

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

The potential psychological benefits of Active Video Games in the rehabilitation of musculoskeletal injuries and deficiencies: A narrative review of the literature

Background: Recent literature suggests that Active Video Games (AVGs) may offer potential psychological benefits during the rehabilitation of musculoskeletal injuries and their corresponding deficiencies. Objectives: To review existing literature regarding the potential psychological benefits of AVGs within the context of rehabilitation from musculoskeletal injury or debilitation. Method: A narrative review of the literature that used the Population, Intervention, Comparison, and Outcomes PICO method was conducted. The literature review included studies that discussed and/or investigated potential psychological benefits of AVGs during musculoskeletal rehabilitation. Of the total 163 papers that were identified, 30 met the inclusion criteria. Results: The Nintendo® WiiTM (Nintendo Co., Ltd, Kyoto, Japan) was the most commonly-used games console that was employed in AVG interventions (15 out of 21), and these studies that investigated potential psychological benefits were typically conducted with elderly populations. These studies reported that using AVGs in musculoskeletal rehabilitation resulted in a number of positive psychological effects (e.g., enjoyment, effects on self). However, most studies lacked a clear theoretical framework, and varied greatly in their designs and methodologies. Conclusion: Despite encouraging findings of AVG use, insufficient evidence exists to reliably verify or refute the potential psychological benefits of AVGs in musculoskeletal rehabilitation. It is recommended that future studies in this area contain a theoretical framework to ensure greater consistency in the methodology used and the execution of the intervention. The potential findings of such investigations may result in the development of optimal, client-tailored rehabilitation programmes

Developmental Acquisition of a Rapid Calcium-Regulated Vesicle Supply Allows Sustained High Rates of Exocytosis in Auditory Hair Cells

Auditory hair cells (HCs) have the remarkable property to indefinitely sustain high rates of synaptic vesicle release during ongoing sound stimulation. The mechanisms of vesicle supply that allow such indefatigable exocytosis at the ribbon active zone remain largely unknown. To address this issue, we characterized the kinetics of vesicle recruitment and release in developing chick auditory HCs. Experiments were done using the intact chick basilar papilla from E10 (embryonic day 10) to P2 (two days post-hatch) by monitoring changes in membrane capacitance and Ca2+ currents during various voltage stimulations. Compared to immature pre-hearing HCs (E10-E12), mature post-hearing HCs (E18-P2) can steadily mobilize a larger readily releasable pool (RRP) of vesicles with faster kinetics and higher Ca2+ efficiency. As assessed by varying the inter-pulse interval of a 100 ms paired-pulse depolarization protocol, the kinetics of RRP replenishment were found much faster in mature HCs. Unlike mature HCs, exocytosis in immature HCs showed large depression during repetitive stimulations. Remarkably, when the intracellular concentration of EGTA was raised from 0.5 to 2 mM, the paired-pulse depression level remained unchanged in immature HCs but was drastically increased in mature HCs, indicating that the Ca2+ sensitivity of the vesicle replenishment process increases during maturation. Concomitantly, the immunoreactivity of the calcium sensor otoferlin and the number of ribbons at the HC plasma membrane largely increased, reaching a maximum level at E18-P2. Our results suggest that the efficient Ca2+-dependent vesicle release and supply in mature HCs essentially rely on the concomitant engagement of synaptic ribbons and otoferlin at the plasma membrane

Incidence and Outcome of Acute Phosphate Nephropathy in Iceland

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Oral sodium phosphate solutions (OSPS) are widely used for bowel cleansing prior to colonoscopy and other procedures. Cases of renal failure due to acute phosphate nephropathy following OSPS ingestion have been documented in recent years, questioning the safety of OSPS. However, the magnitude of the problem remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a population based, retrospective analysis of medical records and biopsies of all cases of acute phosphate nephropathy that were diagnosed in our country in the period from January 2005 to October 2008. Utilizing the complete official sales figures of OSPS, we calculated the incidence of acute phosphate nephropathy in our country. Fifteen cases of acute phosphate nephropathy were diagnosed per 17,651 sold doses of OSPS (0.085%). Nine (60%) were women and mean age 69 years (range 56-75 years). Thirteen patients had a history of hypertension (87%) all of whom were treated with either ACE-I or ARB and/or diuretics. One patient had underlying DM type I and an active colitis and one patient had no risk factor for the development of acute phosphate nephropathy. Average baseline creatinine was 81.7 µmol/L and 180.1 at the discovery of acute renal failure, mean 4.2 months after OSPS ingestion. No patient had a full recovery of renal function, and at the end of follow-up, 26.6 months after the OSPS ingestion, the average creatinine was 184.2 µmol/L. The average eGFR declined from 73.5 ml/min/1.73 m(2) at baseline to 37.3 ml/min/1.73 m(2) at the end of follow-up. One patient reached end-stage renal disease and one patient died with progressive renal failure. CONCLUSION/SIGNIFICANCE: Acute phosphate nephropathy developed in almost one out of thousand sold doses of OSPS. The consequences for kidney function were detrimental. This information can be used in other populations to estimate the impact of OSPS. Our data suggest that acute phosphate nephropathy may be greatly underreported worldwide

No evidence for circulating HuD-specific CD8+ T cells in patients with paraneoplastic neurological syndromes and Hu antibodies

Aim: In paraneoplastic neurological syndromes (PNS) associated with small cell lung cancer (SCLC) and Hu antibodies (Hu-PNS), Hu antigens expressed by the tumour hypothetically trigger an immune response that also reacts with Hu antigens in the nervous system, resulting in tumour suppression and neuronal damage. To gain more insight into the hypothesized CD8+T cell-mediated immune pathogenesis of these syndromes, we searched for circulating HuD-specific CD8+T cells in a large cohort of Hu-PNS patients and controls. Patients and methods: Blood was tested from 43 Hu-PNS patients, 31 Hu antibody negativ

Super-resolution imaging as a method to study GPCR dimers and higher-order oligomers

The study of G protein-coupled receptor (GPCR) dimers and higher-order oligomers has unveiled mechanisms for receptors to diversify signaling and potentially uncover novel therapeutic targets. The functional and clinical significance of these receptor–receptor associations has been facilitated by the development of techniques and protocols, enabling researchers to unpick their function from the molecular interfaces, to demonstrating functional significance in vivo, in both health and disease. Here we describe our methodology to study GPCR oligomerization at the single-molecule level via super-resolution imaging. Specifically, we have employed photoactivated localization microscopy, with photoactivatable dyes (PD-PALM) to visualize the spatial organization of these complexes to <10 nm resolution, and the quantitation of GPCR monomer, dimer, and oligomer in both homomeric and heteromeric forms. We provide guidelines on optimal sample preparation, imaging parameters, and necessary controls for resolving and quantifying single-molecule data. Finally, we discuss advantages and limitations of this imaging technique and its potential future applications to the study of GPCR function

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

\ua9 2023, The Author(s).BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485