Antarctic offshore polynyas linked to Southern Hemisphere climate anomalies.

Offshore Antarctic polynyas-large openings in the winter sea ice cover-are thought to be maintained by a rapid ventilation of deep-ocean heat through convective mixing. These rare phenomena may alter abyssal properties and circulation, yet their formation mechanisms are not well understood. Here we demonstrate that concurrent upper-ocean preconditioning and meteorological perturbations are responsible for the appearance of polynyas in the Weddell Sea region of the Southern Ocean. Autonomous profiling float observations-collected in 2016 and 2017 during the largest polynyas to form near the Maud Rise seamount since 1976-reveal that the polynyas were initiated and modulated by the passage of severe storms, and that intense heat loss drove deep overturning within them. Wind-driven upwelling of record strength weakened haline stratification in the upper ocean, thus favouring destabilization in 2016 and 2017. We show that previous Weddell polynyas probably developed under similarly anomalous conditions, which are associated with a mode of Southern Hemisphere climate variability that is predicted to strengthen as a result of anthropogenic climate change.

Molecular-Modified Photocathodes for Applications in Artificial Photosynthesis and Solar-to-Fuel Technologies.

Nature offers inspiration for developing technologies that integrate the capture, conversion, and storage of solar energy. In this review article, we highlight principles of natural photosynthesis and artificial photosynthesis, drawing comparisons between solar energy transduction in biology and emerging solar-to-fuel technologies. Key features of the biological approach include use of earth-abundant elements and molecular interfaces for driving photoinduced charge separation reactions that power chemical transformations at global scales. For the artificial systems described in this review, emphasis is placed on advancements involving hybrid photocathodes that power fuel-forming reactions using molecular catalysts interfaced with visible-light-absorbing semiconductors.

Perceptions of friendship, peers and influence on adolescent smoking according to tobacco control context: a systematic review and meta-ethnography of qualitative research.

BACKGROUND: A relationship between smoking and interpersonal influences has been well established within the literature. There have been cultural shifts in denormalisation and a reduction in tobacco smoking in many countries. Hence there is a need to understand social influences on adolescents' smoking across smoking normalisation contexts. METHODS: The search was conducted in July 2019 and updated in March 2022 within 11 databases and secondary sources. Search terms included schools, adolescents, smoking, peers, social norms and qualitative research. Screening was conducted by two researchers independently and in duplicate. Study quality was assessed using the eight-item Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-centre) tool for the appraisal of qualitative studies. Results were synthesised using a meta-narrative lens for meta-ethnography and compared across smoking normalisation contexts. RESULTS: Forty one studies were included and five themes were developed, mapping onto the socio ecological model. The social processes by which adolescents take up smoking differed according to a mixture of school type, peer group structure and the smoking culture within the school, as well as the wider cultural context. Data available from smoking denormalised contexts, described changes in social interactions around smoking to cope with its stigmatisation. This was manifested through i) direct peer influence, whereby subtle techniques were employed, ii) group belonging whereby smoking was less likely to be seen as a key determinant of group membership and smoking was less commonly reported to be used as a social tool, and iii) popularity and identity construction, whereby smoking was perceived more negatively in a denormalised context, compared with a normalised context. CONCLUSIONS: This meta-ethnography is the first study to demonstrate, drawing on international data, that peer processes in adolescent smoking may undergo changes as smoking norms within society change. Future research should focus on understanding differences across socioeconomic contexts, to inform the adaptation of interventions.

A qualitative exploration of stakeholder perspectives on the implementation of a whole school approach to mental health and emotional well-being in Wales.

Early intervention to support mental health and well-being of school-aged children may be of significant benefit in preventing escalation of mental health problems in later life. While there are limitations to current understanding of the best ways for schools to support mental well-being, a whole school approach (WSA), involving all those who are part of the school system in creating and sustaining a supportive environment where health is prioritized, may be effective. This research explored stakeholder views of this approach, as part of a contract commissioned by the Welsh Government to conduct an evaluability assessment of a WSA. Semistructured focus groups and interviews were completed with stakeholders from the health and education sectors, as well as parents, to explore how a WSA may operate in a Welsh context and barriers and facilitators to potential implementation and outcomes. Findings suggest that existing pressures on schools may impact implementation of a WSA, with school staff already time poor and many staff experiencing their own mental well-being challenges. Implementation may be supported by clear guidance at local and national levels, funding for staff time and training and stakeholder involvement at all stages. Long-term monitoring and evaluation are also needed to understand system changes.

Exploring the association between school-based peer networks and smoking according to socioeconomic status and tobacco control context: a systematic review.

BACKGROUND: Whilst prevalence of youth smoking in middle and high income countries has decreased, inequality has prevailed. The introduction of legislation regulating tobacco use in public spaces varies across countries, impacting the tobacco control context. Thus reviewing our knowledge of how social networks may influence smoking differently within different contexts is required to facilitate the development of context-specific interventions. METHODS: The search, conducted on 31st May 2019, included the following smoking-related terms; schools, adolescents, peers and social networks. Inclusion and exclusion criteria were applied throughout the title and abstract screening and full text screening. Quality assessment and synthesis followed. Studies were narratively synthesised to identify changes according to legislative context. This synthesis was conducted separately for findings relating to three categories: socioeconomic status; social selection and influence; and network position. RESULTS: Thirty studies were included. Differences in the relationship between network characteristics and smoking according to socioeconomic status were measured in five out of fifteen studies in Europe. Results varied across studies, with differences in network characteristics and their association with smoking varying both between schools of a differing and those of a similar socioeconomic composition. For studies conducted both before and after the introduction of comprehensive smoking legislation, the evidence for selection processes was more consistent than influence, which varied according to reciprocity. Findings showed that isolates were more likely to smoke and in-degree and out-degree centrality were related to smoking both before and after the introduction of legislation. The relationship between popularity and smoking was contingent on school level smoking prevalence in studies conducted before the introduction of legislation, but not after. CONCLUSIONS: Overall, effects according to socioeconomic status were underreported in the included studies and no consistent evidence of change after the introduction of a comprehensive smoking ban was observed. Further network analyses are required using more recent data to obtain a comprehensive understanding of how network processes may influence smoking differently according to socioeconomic status, and how adaptation could be used to enhance intervention effectiveness. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42019137358 .

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain.

PURPOSE: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T1D. METHODS: ihMT ratio (ihMTR) and MWF maps were acquired at 7 T from formalin-fixed human brain samples at 22.5 °C, 30 °C and 37 °C. The impact of temperature on unfiltered ihMTR, filtered ihMTR and MWF was investigated and compared to myelin basic protein staining. RESULTS: Unfiltered ihMTR exhibited no temperature dependence, whereas filtered ihMTR increased with increasing temperature. MWF decreased at higher temperature, with an increasing prevalence of areas where the myelin water signal was unreliably determined, likely related to a reduction in T2 peak separability at higher temperatures ex vivo. MWF and ihMTR showed similar per-sample correlation with myelin staining at room temperature. At 37 °C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR. CONCLUSIONS: Given the temperature dependence of filtered ihMT, increased dynamic range, and strong myelin specificity that persists at higher temperatures, we recommend carefully controlled temperatures close to 37 °C for filtered ihMT acquisitions. Unfiltered ihMT may also be useful, due to its independence from temperature, higher amplitude values, and sensitivity to short T1D components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures.

Recent Progress in Electrochemical pH-Sensing Materials and Configurations for Biomedical Applications.

pH-sensing materials and configurations are rapidly evolving toward exciting new applications, especially those in biomedical applications. In this review, we highlight rapid progress in electrochemical pH sensors over the past decade (2008-2018) with an emphasis on key considerations, such as materials selection, system configurations, and testing protocols. In addition to recent progress in optical pH sensors, our main focus in this review is on electromechanical pH sensors due to their significant advances, especially in biomedical applications. We summarize developments of electrochemical pH sensors that by virtue of their optimized material chemistries (from metal oxides to polymers) and geometrical features (from thin films to quantum dots) enable their adoption in biomedical applications. We further present an overview of necessary sensing standards and protocols. Standards ensure the establishment of consistent protocols, facilitating collective understanding of results and building on the current state. Furthermore, they enable objective benchmarking of various pH-sensing reports, materials, and systems, which is critical for the overall progression and development of the field. Additionally, we list critical issues in recent literary reporting and suggest various methods for objective benchmarking. pH regulation in the human body and state-of-the-art pH sensors (from ex vivo to in vivo) are compared for suitability in biomedical applications. We conclude our review by (i) identifying challenges that need to be overcome in electrochemical pH sensing and (ii) providing an outlook on future research along with insights, in which the integration of various pH sensors with advanced electronics can provide a new platform for the development of novel technologies for disease diagnostics and prevention.

Change over time in adolescent smoking, cannabis use and their association: findings from the School Health Research Network in Wales.

BACKGROUND: While tobacco smoking has declined among UK youth in recent decades, cannabis use has begun to show some growth. Given their interrelationship, growth in cannabis use may act as a barrier to continued reduction in youth smoking. This paper assesses recent tobacco and cannabis use trends in Wales, and their association, to explore whether change in cannabis use might have impacted youth tobacco smoking prevalence. METHODS: Repeat cross-sectional data on tobacco and cannabis use were obtained from biennial Welsh Student Health and Wellbeing surveys between 2013 and 2019. Data were pooled and analysed using logistic regression with adjustment for school-level clustering. RESULTS: No change in regular youth tobacco smoking was observed between 2013 and 2019. In contrast, current cannabis use increased during this time, and cannabis users had significantly greater odds of regular tobacco smoking. After adjusting for change in cannabis use, a significant decline in youth tobacco smoking was observed (OR 0.95; 95% confidence intervals: 0.92, 0.97). CONCLUSION: Recent growth in cannabis use among young people in Wales may have offset prospective declines in regular tobacco smoking. Further reductions in youth smoking may require more integrated policy approaches to address the co-use of tobacco and cannabis among adolescents.

Adapting evidence-informed population health interventions for new contexts: a scoping review of current practice.

BACKGROUND: Implementing evidence-informed population health interventions in new contexts often requires adaptations. While the need to adapt interventions to better fit new contexts is recognised, uncertainties remain regarding why and when to adapt (or not), and how to assess the benefits (or not) of adaptation. The ADAPT Study aims to develop comprehensive guidance on adaptation. This scoping review informs guidance development by mapping and exploring how adaptation has been undertaken in practice, in public health and health services research. METHODS: We searched seven databases from January 2000 and October 2018 to identify eligible studies for this scoping review and a related systematic review of adaptation guidance. We mapped the studies of adaptation by coding data from all eligible studies describing the methods, contexts, and interventions considered for adaptation. From this map, we selected a sample of studies for in-depth examination. Two reviewers extracted data independently into seven categories: description, key concepts, types, rationale, processes, evaluation methods, evaluation justification, and accounts of failures and successes. RESULTS: We retrieved 6694 unique records. From 429 records screened at full text, we identified 298 eligible studies for mapping and selected 28 studies for in-depth examination. The majority of studies in our map focused on micro- (i.e., individual-) level interventions (84%), related to transferring an intervention to a new population group within the same country (62%) and did not report using guidance (73%). Studies covered a range of topic areas, including health behaviour (24%), mental health (19%), sexual health (16%), and parenting and family-centred interventions (15%). Our in-depth analysis showed that adaptation is seen to save costs and time relative to developing a new intervention, and to enhance contextual relevance and cultural compatibility. It commonly follows a structured process and involves stakeholders to help with decisions on what to adapt, when, and how. CONCLUSIONS: Adaptation has been undertaken on a range of health topics and largely in line with existing guidance. Significant gaps relate to adaptation of macro- (e.g., national-) level interventions, consideration of programme theories, mechanisms and contexts (i.e., a functional view of interventions), nuances around stakeholder involvement, and evaluation of the adapted interventions. Registration Open Science Framework, 2019, osf.io/udzma.

Representation of Spatial Variability of the Water Fluxes over the Congo Basin Region.

The Congo Basin, being one of the major basins in the tropics, is important to the global climate, yet its hydrology is perhaps the least understood. Although various reanalysis/analysis datasets have been used to improve our understanding of the basin's hydroclimate, they have been historically difficult to validate due to sparse in situ measurements. This study analyzes the impact of model resolution on the spatial variability of the Basin's hydroclimate using the Decorrelation Length Scale (DLCS) technique, as it is not subject to uniform model bias. The spatial variability within the precipitation (P), evaporation/evapotranspiration (E), and precipitation-minus-evaporation (P-E) fields were investigated across four spatial resolutions using reanalysis/analysis datasets from the ECMWF ranging from 9-75 km. Results show that the representation of P and P-E fields over the Basin and the equatorial Atlantic Ocean are sensitive to model resolution, as the spatial patterns of their DCLS results are resolution-dependent. However, the resolution-independent features are predominantly found in the E field. Furthermore, the P field is the dominant source of spatial variability of P-E, occurring over the land and the equatorial Atlantic Ocean, while over the Southern Atlantic, P-E is mainly governed by the E field, with both showing weak spatial variability.

The role of extrolites secreted by nonaflatoxigenic Aspergillus flavus in biocontrol efficacy.

AIMS: Field control of aflatoxin contamination is thought to occur through competitive exclusion of native aflatoxigenic fungi by introduced nonaflatoxigenic Aspergillus flavus biocontrol strains. In this study, we explored another possible mechanism that could increase the efficacy of biocontrol strains-the production of secreted compounds termed extrolites. METHODS AND RESULTS: Using four Aspergillus strains (one nonaflatoxigenic and three aflatoxigenic) from the same geographic region (Louisiana), we devised experiments whereby each aflatoxigenic strain was grown on media that had first been colonized by the nonaflatoxigenic strain. We observed noticeable reduction in growth and reduced production of aflatoxin and cyclopiazonic acid for all three aflatoxigenic strains when grown in the presence of extrolite secretions from the nonaflatoxigenic strain. CONCLUSIONS: We provide evidence that biocontrol strain extrolites may improve the efficacy of pre and postharvest aflatoxin reduction. SIGNIFICANCE AND IMPACT OF THE STUDY: Our finding, that extrolites secreted by nonaflatoxigenic A. flavus strains potentially abate growth and toxin levels of aflatoxin-producing strains, should allow for us to elucidate the mechanism of how the reduction in toxigenic strains occurs, and potentially identify better biocontrol strains. Identification and isolation of the active extrolites may afford a supplemental method to mitigate aflatoxin production.

Process evaluation of the healthy primary School of the Future: the key learning points.

BACKGROUND: While schools have potential to contribute to children's health and healthy behaviour, embedding health promotion within complex school systems is challenging. The 'Healthy Primary School of the Future' (HPSF) is an initiative that aims to integrate health and well-being into school systems. Central to HPSF are two top-down changes that are hypothesized as being positively disruptive to the Dutch school system: daily free healthy lunches and structured physical activity sessions. These changes are expected to create momentum for bottom-up processes leading to additional health-promoting changes. Using a programme theory, this paper explores the processes through which HPSF and the school context adapt to one another. The aim is to generate and share knowledge and experiences on how to implement changes in the complex school system to integrate school health promotion. METHODS: The current study involved a mixed methods process evaluation with a contextual action-oriented research approach. The processes of change were investigated in four Dutch primary schools during the development year (2014-2015) and the first two years of implementation (2015-2017) of HPSF. The schools (each with 15-26 teachers and 233-389 children) were in low socio-economic status areas. Measurements included interviews, questionnaires, observations, and analysis of minutes of meetings. RESULTS: Top-down advice, combined with bottom-up involvement and external practical support were key facilitators in embedding HPSF within the schools' contexts. Sufficient coordination and communication at the school level, team cohesion, and feedback loops enhanced implementation of the changes. Implementation of the healthy lunch appeared to be disruptive and create momentum for additional health-promoting changes. CONCLUSIONS: Initiating highly visible positive disruptions to improve school health can act as a catalyst for wider school health promotion efforts. Conditions to create a positive disruption are enough time, and sufficient bottom-up involvement, external support, team cohesion and coordination. The focus should be on each specific school, as each school has their own starting point and process of change. TRIAL REGISTRATION: The study was retrospectively registered in the ClinicalTrials.gov database on 14 June 2016 (NCT02800616).

A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly.

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.

Newly developed dilute Russell's viper venom reagents for lupus anticoagulant detection with improved specificity.

Background Dilute Russell's viper venom time (dRVVT) is indispensible in lupus anticoagulant (LA) detection yet commercial reagents from different suppliers perform variably, no gold standard assays exist and therapeutic anticoagulation interference is problematic. Objective The objective of this study was to compare a new formulation dRVVT with two currently available dRVVTs. Materials and methods Life Diagnostics (LD) dRVVT and Stago PTT-LA were routinely used for lupus anticoagulant detection, plus Taipan snake venom time/ecarin time (TSVT/ET) for patients on warfarin or rivaroxaban. Siemens dRVVT and the new HYPHEN BioMed (HBM) dRVVT were tested with 193 patient samples. Group 1, 59 non-anticoagulated patients (NAPs) LA-positive in LD dRVVT; Group 2, 15 PTT-LA-positive/dRVVT-negative NAPs; Group 3, 24 LA-positive warfarinized patients; Group 4, 13 patients on rivaroxaban; Group 5, 62 LA-negative thrombotic NAPs; Group 6, 20 warfarinized, non-antiphospholipid syndrome patients. Results Accepting that the Life Diagnostics reagents were acting as a pseudo-gold standard, Siemens dRVVT detected 56/59, (95%) Group 1 LA and HBM dRVVT 46/59, (76%), one each from Group 2, and Siemens dRVVT detected one in Group 5. The lower HBM dRVVT detection rate mainly concerned weaker LA, where between-reagent concordance is problematic. All Group 3 patients appeared LA-positive in undiluted plasma with Siemens dRVVT, as did 16/24 (67%) with HBM dRVVT but the fewer LA-positives in mixing tests better mapped to clear LA-positives with LD dRVVT. LD and Siemens dRVVTs exhibited 87% and 95% false-positivity for Group 6 whilst HBM dRVVT had none. Increasing the cut-off improved accuracy. Applying higher cut-offs improved accuracy in Group 4 patients. Conclusion HBM dRVVT exhibited improved specificity, mainly due to less interference by anticoagulation, but reduced sensitivity, compared to the other dRVVTs employed.

Deconstructing knowledge brokering for commissioned rapid reviews: an observational study.

BACKGROUND: Knowledge brokers are increasingly used by policy agencies, yet little is known about how they engage with policy-makers and facilitate discussions with them about their research needs. This study examines knowledge brokers' behaviour in one-off interactions with policy-makers commissioning rapid reviews. It describes how knowledge brokers engage with policy-makers, build trust and gain agreement about the review's parameters. METHODS: We observed and transcribed 15 structured knowledge brokering sessions and used line-by-line analysis to derive, test and refine a coding schedule. The final coding schedule was applied to all transcripts. We assigned 35 codes to three tasks identified in the data, namely eliciting information, exploring the policy context and negotiating the content of reviews. RESULTS: The knowledge brokers we observed were skilled facilitators who built trust by their open stance, neutrality, and knowledge of research and policy contexts. Trust engendered an interplay of expertise in which review questions and scope were clarified and contextual factors evaluated. Negotiation about the content of the review focused on understanding how it would contribute to the policy process, comparing options and assessing feasibility. Key functions of knowledge brokers included eliciting and clarifying information, linking the review questions to the context and purpose, moving fluidly between policy and research perspectives, and weighing up review options against policy objectives. Four knowledge brokering roles were identified, namely diagnostic, facilitative, deliberative and interpretative. CONCLUSIONS: This study identified ways in which knowledge brokers established rapport with policy-makers who commissioned reviews, enabled disclosure of essential information and explored contextual factors that affected the review's purpose and intended use. Knowledge brokers were competent in the discourse and conventions of both policy and research and were skilled in negotiating complex policy and political environments, assisting policy-makers to evaluate options and craft a review proposal that was targeted, responsive and feasible. Mutuality, respect and an interplay of expertise were integral to the knowledge brokering process. Future research might usefully examine whether other rapid review programmes using knowledge brokers have similar results as well as the transferability of the four knowledge brokering roles to other contexts and settings.

In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses.

Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B2 (TXB2 ) and Prostaglandin E2 (PGE2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.

Myelin regulatory factor drives remyelination in multiple sclerosis.

Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors has been differentially compared between remyelinating lesions and lesions refractory to remyelination. In particular, the oligodendrocyte transcription factor myelin regulatory factor (MYRF) is essential for myelination during development, but its role during remyelination and expression in MS lesions is unknown. To understand the role of MYRF during remyelination, we genetically fate mapped OPCs following lysolecithin-induced demyelination of the corpus callosum in mice and determined that MYRF is expressed in new oligodendrocytes. OPC-specific Myrf deletion did not alter recruitment or proliferation of these cells after demyelination, but decreased the density of new glutathione S-transferase π positive oligodendrocytes. Subsequent remyelination in both the spinal cord and corpus callosum is highly impaired following Myrf deletion from OPCs. Individual OPC-derived oligodendrocytes, produced in response to demyelination, showed little capacity to express myelin proteins following Myrf deletion. Collectively, these data demonstrate a crucial role of MYRF in the transition of oligodendrocytes from a premyelinating to a myelinating phenotype during remyelination. In the human brain, we find that MYRF is expressed in NogoA and CNP-positive oligodendrocytes. In MS, there was both a lower density and proportion of oligodendrocyte lineage cells and NogoA+ oligodendrocytes expressing MYRF in chronically demyelinated lesions compared to remyelinated shadow plaques. The relative scarcity of oligodendrocyte lineage cells expressing MYRF in demyelinated MS lesions demonstrates, for the first time, that chronic lesions lack oligodendrocytes that express this necessary transcription factor for remyelination and supports the notion that a failure to fully differentiate underlies remyelination failure.

Cobalt Porphyrin-Polypyridyl Surface Coatings for Photoelectrosynthetic Hydrogen Production.

Hybrid materials that link light capture and conversion technologies with the ability to drive reductive chemical transformations are attractive as components in photoelectrosynthetic cells. We show that thin-film polypyridine surface coatings provide a molecular interface to assemble cobalt porphyrin catalysts for hydrogen evolution onto a visible-light-absorbing p-type gallium phosphide semiconductor. Spectroscopic techniques, including grazing angle attenuated total reflection Fourier transform infrared spectroscopy, confirm that the cobalt centers of the porphyrin macrocycles coordinate to pyridyl nitrogen sites of the organic surface coating. The cobalt porphyrin surface concentration and fraction of pyridyl sites coordinated to a cobalt center are quantified using complementary methods of ellipsometry, inductively coupled plasma mass spectrometry, and X-ray photoelectron spectroscopy. In aqueous solutions under simulated solar illumination the modified cathode is photochemically active for hydrogen production, generating the product gas with near-unity Faradaic efficiency at a rate of ≈10 µL min-1 cm-2 when studied in a three-electrode configuration and polarized at the equilibrium potential of the H+/H2 couple. This equates to a photoelectrochemical hydrogen evolution reaction activity of 17.6 H2 molecules s-1 Co-1, the highest value reported to date for a molecular-modified semiconductor. Key features of the functionalized photocathode include (1) the relative ease of synthetic preparation made possible by application of an organic surface coating that provides molecular recognition sites for immobilizing the cobalt porphyrin complexes at the semiconductor surface and (2) the use of visible light to drive cathodic fuel-forming reactions in aqueous solutions with no added organic acids or sacrificial chemical reductants.

Patients with inflammatory bowel disease and their treating clinicians have different views regarding diet.

BACKGROUND: Diet and body composition play unclear roles in the pathogenesis, activity and symptoms of inflammatory bowel disease (IBD). Evidence-based guidance regarding dietary modification in IBD is lacking. We aimed to determine the attitudes of IBD patients and clinicians to diet. METHODS: The present cross-sectional study comprised an online questionnaire distributed to members of a national IBD patient organisation, assessing demographics, anthropometry, disease phenotype and dietary beliefs. Dietitians, gastroenterologists and surgeons were targeted for a similar questionnaire as a result of membership of national professional bodies. RESULTS: Nine hundred and twenty-eight patients (72.2% female; mean age 39.5 years; age range 5-91 years) responded. Two-thirds of the patients had Crohn's disease. The mean reported body mass index was 24.9 kg m-2 and was significantly skewed to the right. Patients who had taken >10 courses of steroids were had a greater probability of being overweight or obese, independent of disease complications. Most patients (71%) assumed that their diet affected their IBD; 61% considered their IBD specialist disregarded the importance of diet. Of the 136 clinicians who responded, the majority felt that diet was a factor in symptoms and intestinal microbiota. More gastroenterologists (44%) than dietitians (17%) considered that diet had a role in the pathogenesis of IBD (P = 0.003). Twenty-six percent of patients reported receiving dietary advice from their IBD specialist, whereas 98% of gastroenterologists reported advice provision. Patients received diverse advice. Half of the patients followed recommendations provided by a clinician. CONCLUSIONS: The present study demonstrates that IBD patients consider diet to be important in their disease. IBD clinicians from different disciplines have diverse views of the role of diet. Advice given to patients is heterogeneous, often perceived as inadequate and poorly followed.