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The scission and homologation of CO is a fundamental process in the Fischer-Tropsch reaction. However, given the heterogeneous nature of the catalyst and forcing reaction conditions, it is difficult to determine the intermediates of this reaction. Here we report detailed mechanistic insight into the scission/homologation of CO by two-coordinate iron terphenyl complexes. Mechanistic investigations, conducted using in situ monitoring and reaction sampling techniques (IR, NMR, EPR and Mössbauer spectroscopy) and structural characterisation of isolable species, identify a number of proposed intermediates. Crystallographic and IR spectroscopic data reveal a series of migratory insertion reactions from 1Mes to 4Mes. Further studies past the formation of 4Mes suggest that ketene complexes are formed en route to squaraine 2Mes and iron carboxylate 3Mes, with a number of ketene containing structures being isolated, in addition to the formation of unbound, protonated ketene (8). The synthetic and mechanistic studies are supported by DFT calculations.
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The Vendée Globe is a non-stop, unassisted, single-handed round the world sailing race. It is regarded as the toughest sailing race, requiring high cognitive functioning and constant alertness. Little is known about the amount of sleep restriction and nutritional deficit experienced at sea and effects that fatigue have on sailors' performance. This report aimed to investigate these aspects by monitoring one of the female participants of the latest Vendée Globe. Sleep, food intake and stress were self-reported daily using specific app. Cognitive assessments were digitally completed. Heart rate and activity intensity were measured using a wrist-worn wearable device. Mean self-report sleep duration per 24 h was 3 hours 40 minutes. By the end of the 95 race days, the sailor reached a caloric deficit of 27,900 kcal. On average, the sailor spent 50 minutes per day in moderate-to-vigorous activity. Cognitive assessments did not show any effect of fatigue or stress on completion time or performance. Recent technological and communication advancement for offshore sailors, enabled continuous data to be monitored in near real time, even from the Southern Ocean. Moving forward this will enable greater understanding of when sailors will be at risk of poor decision making, illness or injury.
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Fadiga , Frequência Cardíaca , Esportes Aquáticos , Humanos , Feminino , Esportes Aquáticos/fisiologia , Frequência Cardíaca/fisiologia , Adulto , Cognição/fisiologia , Navios , Sono/fisiologia , Desempenho Atlético/fisiologia , Ingestão de Energia/fisiologia , Privação do Sono/fisiopatologia , Ingestão de Alimentos/fisiologia , Autorrelato , Comportamento Competitivo/fisiologia , Dispositivos Eletrônicos VestíveisRESUMO
Importance: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. Objective: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. Design, Setting, And Participants: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. Interventions: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. Main Outcomes And Measures: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). Results: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79â¯000. Conclusions And Relevance: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. Trial Registration: ClinicalTrials.gov Identifier: NCT03916055.
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Análise Custo-Benefício , Síndrome de Tourette , Humanos , Síndrome de Tourette/terapia , Masculino , Feminino , Criança , Adolescente , Seguimentos , Internet , Suécia , Resultado do Tratamento , Intervenção Baseada em Internet , Terapia Comportamental/métodos , Terapia Comportamental/economiaRESUMO
Room-temperature magnetically switchable materials play a vital role in current and upcoming quantum technologies, such as spintronics, molecular switches, and data storage devices. The increasing miniaturization of device architectures produces a need to develop analytical tools capable of precisely probing spin information at the single-particle level. In this work, we demonstrate a methodology using negatively charged nitrogen vacancies (NV-) in fluorescent nanodiamond (FND) particles to probe the magnetic switching of a spin crossover (SCO) metal-organic framework (MOF), [Fe(1,6-naphthyridine)2(Ag(CN)2)2] material (1), and a single-molecule photomagnet [X(18-crown-6)(H2O)3]Fe(CN)6·2H2O, where X = Eu and Dy (materials 2a and 2b, respectively), in response to heat, light, and electron beam exposure. We employ correlative light-electron microscopy using transmission electron microscopy (TEM) finder grids to accurately image and sense spin-spin interacting particles down to the single-particle level. We used surface-sensitive optically detected magnetic resonance (ODMR) and magnetic modulation (MM) of FND photoluminescence (PL) to sense spins to a distance of ca. 10-30 nm. We show that ODMR and MM sensing was not sensitive to the temperature-induced SCO of FeII in 1 as formation of paramagnetic FeIII through surface oxidation (detected by X-ray photoelectron spectroscopy) on heating obscured the signal of bulk SCO switching. We found that proximal FNDs could effectively sense the chemical transformations induced by the 200 keV electron beam in 1, namely, AgI â Ag0 and FeII â FeIII. However, transformations induced by the electron beam are irreversible as they substantially disrupt the structure of MOF particles. Finally, we demonstrate NV- sensing of reversible photomagnetic switching, FeIII + (18-crown-6) â FeII + (18-crown-6)+â¯â¢, triggered in 2a and 2b by 405 nm light. The photoredox process of 2a and 2b proved to be the best candidate for room-temperature single-particle magnetic switching utilizing FNDs as a sensor, which could have applications into next-generation quantum technologies.
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BACKGROUND: Online therapies have been shown to be effective in improving students' mental health. They are cost-effective and therefore have particular advantages in low-income countries like Zambia where mental health resources are limited. This study aimed to explore the perceived impact of the COVID-19 pandemic and the feasibility of implementing an Internet-Based Cognitive Behavioural Therapy (iCBT) intervention ('moodgym') to improve resilience in vulnerable Zambian students. METHODS: The study was a qualitative interview study. Participants identifying as having symptoms of low mood and completing a baseline, online survey (n = 620) had the option to volunteer for a semi-structured interview to explore views about their experience of the pandemic and the acceptability and perceived benefits and limitations of using moodgym. RESULTS: A total of 50 students (n = 24 female, n = 26 male) participated in the study. One theme with 4 sub-themes, captured the severe emotional and social impact of the COVID-19 pandemic. A second, very strong theme, with 5 sub-themes, reflected the considerable negative effects of the pandemic on the students' educational experience. This included the challenges of online learning. The third theme, with three subthemes, captured the benefits and acceptability of moodgym, particularly in terms of understanding the relationship between thoughts and feelings and improving academic performance. The fourth theme described the technical difficulties experienced by students in attempting to use moodgym. CONCLUSION: COVID-19 caused fear and impacted wellbeing in vulnerable students and severely impaired the quality of students' educational experience. The findings suggest that moodgym might be a valuable support to students in a low-income country.
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COVID-19 , Terapia Cognitivo-Comportamental , Humanos , Masculino , Feminino , Pandemias , Pesquisa Qualitativa , Estudantes , InternetRESUMO
Chronic human norovirus (HuNoV) infections in immunocompromised patients result in severe disease, yet approved antivirals are lacking. RNA-dependent RNA polymerase (RdRp) inhibitors inducing viral mutagenesis display broad-spectrum in vitro antiviral activity, but clinical efficacy in HuNoV infections is anecdotal and the potential emergence of drug-resistant variants is concerning. Upon favipiravir (and nitazoxanide) treatment of four immunocompromised patients with life-threatening HuNoV infections, viral whole-genome sequencing showed accumulation of favipiravir-induced mutations which coincided with clinical improvement although treatment failed to clear HuNoV. Infection of zebrafish larvae demonstrated drug-associated loss of viral infectivity and favipiravir treatment showed efficacy despite occurrence of RdRp variants potentially causing favipiravir resistance. This indicates that within-host resistance evolution did not reverse loss of viral fitness caused by genome-wide accumulation of sequence changes. This off-label approach supports the use of mutagenic antivirals for treating prolonged RNA viral infections and further informs the debate surrounding their impact on virus evolution.
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Amidas , Norovirus , Pirazinas , Vírus , Animais , Humanos , Norovirus/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Peixe-Zebra , Mutagênese , RNA Polimerase Dependente de RNA/genética , Hospedeiro ImunocomprometidoRESUMO
BACKGROUND: Newborn screening (NBS) programs for severe combined immunodeficiency facilitate early diagnosis of severe combined immunodeficiency and promote early treatment with hematopoietic stem cell transplantation, resulting in improved clinical outcomes. Infants with congenital athymia are also identified through NBS because of severe T-cell lymphopenia. With the expanding introduction of NBS programs, referrals of athymic patients for treatment with thymus transplantation have recently increased at Great Ormond Street Hospital (GOSH) (London, United Kingdom). OBJECTIVE: We studied the impact of NBS on timely diagnosis and treatment of athymic infants with thymus transplantation at GOSH. METHODS: We compared age at referral and complications between athymic infants diagnosed after clinical presentation (n = 25) and infants identified through NBS (n = 19) who were referred for thymus transplantation at GOSH between October 2019 and February 2023. We assessed whether age at time of treatment influences thymic output at 6 and 12 months after transplantation. RESULTS: The infants referred after identification through NBS were significantly younger and had fewer complications, in particular fewer infections. All deaths occurred in the group of those who did not undergo NBS, including 6 patients before and 2 after thymus transplantation because of preexisting infections. In the absence of significant comorbidities or diagnostic uncertainties, timely treatment was achieved more frequently after NBS. Treatment when younger than age 4 months was associated with higher thymic output at 6 and 12 months after transplantation. CONCLUSION: NBS contributes to earlier recognition of congenital athymia, promoting referral of athymic patients for thymus transplantation before they acquire infections or other complications and facilitating treatment at a younger age, thus playing an important role in improving their outcomes.
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Síndromes de Imunodeficiência , Imunodeficiência Combinada Severa , Lactente , Recém-Nascido , Humanos , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Triagem Neonatal , TimoRESUMO
Background: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms: Two serious, unrelated adverse events occurred in the control group. Limitations: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.
It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 917 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy.
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Transtornos de Tique , Tiques , Criança , Humanos , Masculino , Adolescente , Feminino , Análise Custo-Benefício , Método Simples-Cego , Terapia Comportamental , Qualidade de VidaRESUMO
BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.
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Variação Genética , Doenças Raras , Humanos , Doenças Raras/diagnóstico , Doenças Raras/genética , Sequenciamento Completo do Genoma , Testes Genéticos , Mutação , Proteínas de Ciclo CelularRESUMO
Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.
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Fatores de Transcrição Box Pareados , Imunodeficiência Combinada Severa , Humanos , Fatores de Transcrição Box Pareados/genética , Fenótipo , Linfócitos T , Timo , Imunodeficiência Combinada Severa/genéticaRESUMO
Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C. albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.
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Evidence-based practices (EBPs) provide strategies to improve the health, welfare and productivity of animal species. However, ensuring implementation and uptake into routine practice of these EBPs is often challenging. In human health research, one approach used to improve uptake of EBPs is the use of theories, models and/or frameworks (TMFs), however the extent of the use of this approach in veterinary medicine is unknown. The aim of this scoping review was to identify existing veterinary uses of TMFs to inform the uptake of EBPs, and to understand the focus of these applications. Searches were conducted in CAB Abstracts, MEDLINE, Embase and Scopus, alongside grey literature, and ProQuest Dissertations & Theses. The search strategy consisted of a list of known existing TMFs that have been used to improve uptake of EBPs in human health, alongside more generic terminology for implementation and terminology relevant to veterinary medicine. Peer reviewed journal articles and grey literature detailing the use of a TMF to inform uptake of EBP(s) in a veterinary context were included. The search identified 68 studies that met the eligibility criteria. Included studies represented a diverse spread of countries, areas of veterinary concern and EBP. A range of 28 different TMFs were used, although the Theory of Planned Behaviour (TPB) predominated, featuring in 46% of included studies (n = 31). The majority of studies (n = 65, 96%) utilised a TMF with the aim to understand and/or explain what influences implementation outcomes. Only 8 studies (12%) reported the use of a TMF alongside/in conjunction with the actual implementation of an intervention. It is clear there has been some use to date of TMFs to inform uptake of EBPs in veterinary medicine, however it has been sporadic. There has been a heavy reliance on usage of the TPB and other similar classic theories. This has typically been to inform the understanding of factors, such as barriers and facilitators, that may influence the outcome of an implementation effort without then applying this knowledge to the actual implementation of an intervention. Furthermore, there has been a lack of acknowledgement of wider contextual factors and consideration of sustainability of interventions. There is clear potential to increase and expand the usage of TMFs to improve uptake of EBPs in veterinary medicine, including utilising a wider range of TMFs and developing interdisciplinary collaborations with human implementation experts.
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Prática Clínica Baseada em Evidências , Medicina Veterinária , Animais , Medicina Veterinária/normasRESUMO
BACKGROUND: Anxiety is a common mental health problem in the general population, and is associated with functional impairment and negative impacts upon quality of life. There has been increased concern about university students' mental health in recent years, with a wide range of non-specific anxiety rates reported worldwide in undergraduate university students. We aimed to explore prevalence of non-specific anxiety in undergraduate university student populations. METHODS: Four databases were searched to identify studies published between 1980 and 2020 which investigated prevalence of non-specific anxiety in undergraduate university students. Each study's quality was appraised using a checklist. Sub-analyses were undertaken reflecting outcome measure utilized, course of study, location of study, and whether study was before or during the COVID-19 pandemic. RESULTS: A total of 89 studies - representing approx. 130,090 students-met inclusion criteria. Eighty-three were included in meta-analysis, calculating a weighted mean prevalence of 39.65% (95% CI: 35.72%-43.58%) for non-specific anxiety. Prevalence from diagnostic interview studies ranged from 0.3%-20.8% 12-month prevalence. Prevalence varied by outcome measure used to assess non-specific anxiety, the type of course studied by sample, and by study location. In half the studies, being female was associated with being more likely to have higher non-specific anxiety scores and/or screening above thresholds. Few of the included studies met all quality appraisal criteria. CONCLUSION: The results suggest that approximately a third of undergraduate students are experiencing elevated levels of non-specific anxiety. Results from sub-analyses have identified some methodological issues that need consideration in appraising prevalence in this population.
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COVID-19 , Pandemias , Humanos , Feminino , Masculino , Universidades , Prevalência , Qualidade de Vida , COVID-19/epidemiologia , Ansiedade/epidemiologia , Estudantes/psicologiaRESUMO
Inborn errors of thymic stromal cell development and function which are associated with congenital athymia result in life-threatening immunodeficiency with susceptibility to infections and autoimmunity. Athymic patients can be treated by thymus transplantation using cultured donor thymus tissue. Outcomes in patients treated at Duke University Medical Center and Great Ormond Street Hospital (GOSH) over the past three decades have shown that sufficient T-cell immunity can be recovered to clear and prevent infections, but post-treatment autoimmune manifestations are relatively common. Whilst thymus transplantation offers the chance of long-term survival, significant challenges remain to optimise the outcomes for the patients. In this review, we will discuss unmet needs and offer practical guidance based on the experience of the European Thymus Transplantation programme at GOSH. Newborn screening (NBS) for severe combined immunodeficiency (SCID) and routine use of next-generation sequencing (NGS) platforms have improved early recognition of congenital athymia and increasing numbers of patients are being referred for thymus transplantation. Nevertheless, there remain delays in diagnosis, in particular when the cause is genetically undefined, and treatment accessibility needs to be improved. The majority of athymic patients have syndromic features with acute and chronic complex health issues, requiring life-long multidisciplinary and multicentre collaboration to optimise their medical and social care. Comprehensive follow up after thymus transplantation including monitoring of immunological results, management of co-morbidities and patient and family quality-of-life experience, is vital to understanding long-term outcomes for this rare cohort of patients. Alongside translational research into improving strategies for thymus replacement therapy, patient-focused clinical research will facilitate the design of strategies to improve the overall care for athymic patients.
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BACKGROUND: Health protective behaviours are crucial in the prevention of the spread of COVID-19, particularly in university students who typically live and study in large groups. Depression and anxiety are common in students and can impact young people's motivations to follow health advice. The study aims to assess the relationship between mental health and COVID-19 health-protective behaviours in Zambian university students with symptoms of low mood. METHODS: The study was a cross-sectional, online survey of Zambian university students. Participants were also invited to take part in a semi-structured interview to explore views about COVID-19 vaccination. Invitation emails were sent explaining the study aims and directed students who self-identified as having low mood in the past two weeks to an online survey. Measures included COVID-19 preventive behaviours, COVID-19-related self-efficacy, and Hospital and Anxiety Depression scale. RESULTS: A total of 620 students (n=308 female, n=306 male) participated in the study, with a mean participant age of 22.47±3.29 years (range 18-51). Students reported a mean protective behaviour score of 74.09/105 and 74% scored above the threshold for possible anxiety disorder. Three-way ANOVA showed lower COVID-19 protective behaviours in students with possible anxiety disorder (p=.024) and those with low self-efficacy (p<0.001). Only 168 (27%) said they would accept vaccination against COVID-19, with male students being twice as likely to be willing to accept COVID-19 vaccination (p<0.001). Of 50 students interviewed. 30 (60%) expressed fears about the vaccination and 16 (32%) were concerned about a lack of information. Only 8 (16%) participants expressed doubts about effectiveness. CONCLUSION: Students who self-identify as having symptoms of depression have high levels of anxiety. The results suggest that interventions to reduce anxiety and promote self-efficacy might enhance students' COVID-19 protective behaviours. Qualitative data provided insight into the high rates of vaccine hesitancy in this population.
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COVID-19 , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Universidades , Vacinas contra COVID-19 , Zâmbia/epidemiologia , Ansiedade/epidemiologia , EstudantesRESUMO
Chiral diketopyrrolopyrroles appended with enantiomeric ethyl lactate functions through an ether linkage to the aryl backbone of the chromophore were synthesized via the Mitsunobu reaction. The molecules have good solubility and excellent optical properties, high molar absorption coefficients, and fluorescence quantum yields. Helical aggregates with circular dichroism arising from the supramolecular arrangement are seen in both solution and thin films, and the aggregates also display circularly polarized luminescence (glum ≈ ±0.1). The molecules assemble to give monolayers on graphite and precipitate from solution forming supramolecular twisted tapes hundreds of microns long.
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BACKGR OUND: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019. METHODS: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years. RESULTS: Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result. CONCLUSION: The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.