BRIL - Capturing Experiments in the Wild

This presentation describes a project to embed a repository system (based on Fedora) within the complex, experimental processes of a number of researchers in biophysics and structural biology. The project is capturing not just individual datasets but entire experimental workflows as complex objects, incorporating provenance information based on the Open Provenance Model, to support reproduction and validation of published results. The repository is integrated within these experimental processes, so that data capture is as far as possible automatic and invisible to the researcher. A particular challenge is that the researchers’ work takes place in local environments within the department, entirely decoupled from the repository. In meeting this challenge, the project is bridging the gap between the “wild”, ad hoc and independent environment of the researchers desktop, and the curated, sustainable, institutional environment of the repository, and in the process project crosses the boundary between several of the pairs of polar opposites identified in the call

BRIL - Capturing Experiments in the Wild

This presentation describes a project to embed a repository system (based on Fedora) within the complex, experimental processes of a number of researchers in biophysics and structural biology. The project is capturing not just individual datasets but entire experimental workflows as complex objects, incorporating provenance information based on the Open Provenance Model, to support reproduction and validation of published results. The repository is integrated within these experimental processes, so that data capture is as far as possible automatic and invisible to the researcher. A particular challenge is that the researchers’ work takes place in local environments within the department, entirely decoupled from the repository. In meeting this challenge, the project is bridging the gap between the “wild”, ad hoc and independent environment of the researchers desktop, and the curated, sustainable, institutional environment of the repository, and in the process project crosses the boundary between several of the pairs of polar opposites identified in the call

Asp-120 Locates Zn2 for Optimal Metallo-β-lactamase Activity

Metallo-β-lactamases are zinc-dependent hydrolases that inactivate β-lactam antibiotics, rendering bacteria resistant to them. Asp-120 is fully conserved in all metallo-β-lactamases and is central to catalysis. Several roles have been proposed for Asp-120, but so far there is no agreed consensus. We generated four site-specifically substituted variants of the enzyme BcII from Bacillus cereus as follows: D120N, D120E, D120Q, and D120S. Replacement of Asp-120 by other residues with very different metal ligating capabilities severely impairs the lactamase activity without abolishing metal binding to the mutated site. A kinetic study of these mutants indicates that Asp-120 is not the proton donor, nor does it play an essential role in nucleophilic activation. Spectroscopic and crystallographic analysis of D120S BcII, the least active mutant bearing the weakest metal ligand in the series, reveals that this enzyme is able to accommodate a dinuclear center and that perturbations in the active site are limited to the Zn2 site. It is proposed that the role of Asp-120 is to act as a strong Zn2 ligand, locating this ion optimally for substrate binding, stabilization of the development of a partial negative charge in the β-lactam nitrogen, and protonation of this atom by a zinc-bound water molecule

IMPLANTAÇÃO DE APLICATIVO PARA FACILITAR AS DEMANDAS DOS CIDADÃOS PARA A PREFEITURA MUNICIPAL DE MATELÂNDIA

Verificando-se a situação de pandemia, chegou-se ao questionamento de como reduzir as distâncias e os deslocamentos da população em busca dos serviços fornecidos em vários setores da Prefeitura de Matelândia-Paraná, especificamente os que são solicitados via setor de Protocolos, proporcionando segurança e comodidade. A ideia inovadora teve o objetivo de propor a criação de uma ferramenta como forma de solução ao problema apresentado, e visou proporcionar a conexão entre as pessoas e os serviços Públicos ofertados pela Prefeitura de Matelândia-PR. A metodologia utilizada foi do tipo observatória, participativa e implementativa. Um desafio significativo em mudar a realidade e trazer os usuários bem como os servidores públicos no mesmo sentido de aceitação de implementação da inovação. Este relato técnico traz a experiência da implementação e dos resultados do aplicativo GEO CIDADÃO, que proporcionou a conexão entre as pessoas e os serviços Públicos ofertados pela Prefeitura de Matelândia, otimizou e tornou mais ágil o serviço público ao cidadão, diminuindo riscos em momentos de pandemia e, desperdício de tempo, bem como gastos com locomoção, e podemos concluir que ela resolveu o problema apresentado, podendo ser aplicada a solução em escala para outros setores e órgãos, considerando suas vantagens já experimentadas.

Joint stiffness is heritable and associated with fibrotic conditions and joint replacement

ObjectiveJoint stiffness is a common, debilitating, age-related symptom, which may be seen after total joint replacement (TJR). Stiffness also occurs in fibrotic conditions such as shoulder capsulitis and Dupuytren's contracture. We speculated that the two traits (TJR and fibrotic disease) are linked pathogenically.MethodsUsing the TwinsUK NIHR BRC BioResource we tested the hypotheses that 1) joint (hip and knee) stiffness, TJR (hip and knee), and fibrotic conditions are associated and 2) genetic factors contribute to them.ResultsParticipating twins (n = 9718) had completed self-reported questionnaires on the traits of interest. All three traits were significantly associated with increasing age and body mass index (BMI), as well as female sex, on univariate analysis. Multivariable logistic regression analyses showed a significant association between TJR and joint stiffness (OR = 3.96, 95% confidence interval, CI 2.77-5.68) and between fibrotic conditions and joint stiffness (OR = 2.39, 1.74-3.29), adjusting for age, sex, BMI and twin relatedness. Monozygotic versus dizygotic intraclass correlations gave heritability estimates for TJR = 46% and joint stiffness = 32%.ConclusionThat fibrotic conditions, joint stiffness and TJR are significantly associated suggests a common disease process, possibly fibrosis, which is genetically mediated

Baseline and acquired resistance to bedaquiline, linezolid and pretomanid, and impact on treatment outcomes in four tuberculosis clinical trials containing pretomanid

Bedaquiline (B), pretomanid (Pa) and linezolid (L) are key components of new regimens for treating rifampicin-resistant tuberculosis (TB). However, there is limited information on the global prevalence of resistance to these drugs and the impact of resistance on treatment outcomes. Mycobacterium tuberculosis (MTB) phenotypic drug susceptibility and whole-genome sequence (WGS) data, as well as patient profiles from 4 pretomanid-containing trials–STAND, Nix-TB, ZeNix and SimpliciTB–were used to investigate the rates of baseline resistance (BR) and acquired resistance (AR) to BPaL drugs, as well as their genetic basis, risk factors and impact on treatment outcomes. Data from >1,000 TB patients enrolled from 2015 to 2020 in 12 countries was assessed. We identified 2 (0.3%) participants with linezolid BR. Pretomanid BR was also rare, with similar rates across TB drug resistance types (0–2.1%). In contrast, bedaquiline BR was more prevalent among participants with highly resistant TB or longer prior treatment histories than those with newly diagnosed disease (5.2–6.3% vs. 0–0.3%). Bedaquiline BR was a risk factor for bacteriological failure or relapse in Nix-TB/ZeNix; 3/12 (25%, 95% CI 5–57%) participants with vs. 6/185 (3.2%, 1.2–6.9%) without bedaquiline BR. Across trials, we observed no linezolid AR, and only 3 cases of bedaquiline AR, including 2 participants with poor adherence. Overall, pretomanid AR was also rare, except in ZeNix patients with bedaquiline BR. WGS analyses revealed novel mutations in canonical resistant genes and, in 7 MTB isolates, the genetic determinants could not be identified. The overall low rates of BR to linezolid and pretomanid, and to a lesser extent to bedaquiline, observed in the pretomanid trials are in support of the worldwide implementation of BPaL-based regimens. Similarly, the overall low AR rates observed suggest BPaL drugs are better protected in the regimens trialed here than in other regimens combining bedaquiline with more, but less effective drugs

Ethnic variations in sexual partnerships and mixing, and their association with STI diagnosis: findings from a cross-sectional biobehavioural survey of attendees of sexual health clinics across England.

OBJECTIVES: Ethnic differences in partnership types and sexual mixing patterns may contribute to elevated STI diagnosis rates among England's Black Caribbean (BC) population. We examined the differences between BC and White British/Irish (WBI) sexual health clinic (SHC) attendees' reported partnerships and sexual mixing, and whether these differences could explain ethnic inequalities in STI, focusing on attendees reporting only opposite-sex partners (past year). METHODS: We surveyed attendees at 16 SHCs across England (May to September 2016), and linked their survey responses to routinely collected data on diagnoses of bacterial STI or trichomoniasis ±6 weeks of clinic attendance ('acute STI'). Behaviourally-heterosexual BC and WBI attendees (n=1790) reported details about their ≤3 most recent opposite-sex partners (past 3 months, n=2503). We compared BC and WBI attendees' reported partnerships and mixing, in gender-stratified analyses, and used multivariable logistic regression to examine whether they independently explained differences in acute STI. RESULTS: We observed differences by ethnic group. BC women's partnerships were more likely than WBI women's partnerships to involve age-mixing (≥5 years age difference; 31.6% vs 25.5% partnerships, p=0.013); BC men's partnerships were more often 'uncommitted regular' (35.4% vs 20.7%) and less often casual (38.5% vs 53.1%) than WBI men's partnerships (p<0.001). Acute STI was higher among BC women than WBI women (OR: 2.29, 95% CI 1.24 to 4.21), with no difference among men. This difference was unaffected by partnerships and mixing: BC women compared with WBI women adjusted OR: 2.31 (95% CI 1.30 to 4.09) after adjusting for age and partner numbers; 2.15 (95% CI 1.07 to 4.31) after additionally adjusting for age-mixing, ethnic-mixing and recent partnership type(s). CONCLUSION: We found that differences in sexual partnerships and mixing do not appear to explain elevated risk of acute STI diagnosis among behaviourally-heterosexual BC women SHC attendees, but this may reflect the measures used. Better characterisation of 'high transmission networks' is needed, to improve our understanding of influences beyond the individual level, as part of endeavours to reduce population-level STI transmission

Efeitos da abordagem interdisciplinar na qualidade de vida e em parâmetros laboratoriais de pacientes com doença renal crônica

CONTEXTO: A abordagem de portadores de doença renal crônica (DRC) em tratamento conservador, por meio de equipes interdisciplinares, pode melhorar a qualidade de vida desses pacientes. OBJETIVOS: Avaliar os efeitos da abordagem interdisciplinar na qualidade de vida de pacientes com DRC em tratamento conservador. MÉTODOS: Setenta e cinco pacientes, acompanhados por equipe interdisciplinar (n = 50) ou por atendimento médico tradicional (n = 25), foram avaliados no início e após um ano de acompanhamento. A qualidade de vida foi avaliada pelo Medical Outcomes Study Questionaire 36 - Item Short Form Health Survey (SF-36), e a análise de parâmetros clínicos e laboratoriais foi obtida com base nos registros dos prontuários médicos. RESULTADOS: Após 1 ano de acompanhamento, os pacientes assistidos por equipe interdisciplinar apresentaram melhora nos seguintes parâmetros do SF-36: capacidade funcional, aspectos físicos, estado geral de saúde, vitalidade e aspectos emocionais; já no grupo-controle esses parâmetros permaneceram inalterados. Além disso, pacientes do grupo interdisciplinar mostraram significativa redução do peso corporal e aumento da hemoglobina e do cálcio plasmáticos. CONCLUSÕES: A abordagem interdisciplinar contribuiu para a melhora da qualidade de vida e para o controle clínico de portadores de DRC em tratamento conservador.BACKGROUND: Multidisciplinary team-based care (MDC) of patients with chronic kidney disease (CKD) before the beginning of the renal replacement therapy may improve their quality of life. OBJECTIVES: This study aimed to assess the impact of MDC on the quality of life patients with CKD not yet on dialysis. METHODS: Seventy five patients treated by MDC (n = 50) or by standard medical care (n = 25) were evaluated at the beginning and after one year of follow-up. Quality of life was assessed by the Medical Outcomes Study Questionnaire 36 - Item Short Form Health Survey (SF-36). Clinical and laboratory parameters were obtained from the patients' charts. RESULTS: After 1-year of follow-up, the patients in MDC improved the following dimensions of the SF-36: functional capacity, physical features, general health, vitality and mood. On the other hand, the control group did not improve any dimension in quality of life. At the end of the study, the patients followed by the MDC lost body weight and showed statistically significant increases in hemoglobin and calcium plasma levels, when compared to control group. DISCUSSION: Our results showed that, compared to the standard medical care, the MDC contributed to achieve a better quality of life and clinical control in patients with CKD not yet on dialysis

Quality of life and improvement of laboratory parameters as an outcome of an interdisciplinary approach to the care of patients with chronic kidney disease

BACKGROUND: Multidisciplinary team-based care (MDC) of patients with chronic kidney disease (CKD) before the beginning of the renal replacement therapy may improve their quality of life. OBJECTIVES: This study aimed to assess the impact of MDC on the quality of life patients with CKD not yet on dialysis. METHODS: Seventy five patients treated by MDC (n = 50) or by standard medical care (n = 25) were evaluated at the beginning and after one year of follow-up. Quality of life was assessed by the Medical Outcomes Study Questionnaire 36 - Item Short Form Health Survey (SF-36). Clinical and laboratory parameters were obtained from the patients' charts. RESULTS: After 1-year of follow-up, the patients in MDC improved the following dimensions of the SF-36: functional capacity, physical features, general health, vitality and mood. On the other hand, the control group did not improve any dimension in quality of life. At the end of the study, the patients followed by the MDC lost body weight and showed statistically significant increases in hemoglobin and calcium plasma levels, when compared to control group. DISCUSSION: Our results showed that, compared to the standard medical care, the MDC contributed to achieve a better quality of life and clinical control in patients with CKD not yet on dialysis.CONTEXTO: A abordagem de portadores de doença renal crônica (DRC) em tratamento conservador, por meio de equipes interdisciplinares, pode melhorar a qualidade de vida desses pacientes. OBJETIVOS: Avaliar os efeitos da abordagem interdisciplinar na qualidade de vida de pacientes com DRC em tratamento conservador. MÉTODOS: Setenta e cinco pacientes, acompanhados por equipe interdisciplinar (n = 50) ou por atendimento médico tradicional (n = 25), foram avaliados no início e após um ano de acompanhamento. A qualidade de vida foi avaliada pelo Medical Outcomes Study Questionaire 36 - Item Short Form Health Survey (SF-36), e a análise de parâmetros clínicos e laboratoriais foi obtida com base nos registros dos prontuários médicos. RESULTADOS: Após 1 ano de acompanhamento, os pacientes assistidos por equipe interdisciplinar apresentaram melhora nos seguintes parâmetros do SF-36: capacidade funcional, aspectos físicos, estado geral de saúde, vitalidade e aspectos emocionais; já no grupo-controle esses parâmetros permaneceram inalterados. Além disso, pacientes do grupo interdisciplinar mostraram significativa redução do peso corporal e aumento da hemoglobina e do cálcio plasmáticos. CONCLUSÕES: A abordagem interdisciplinar contribuiu para a melhora da qualidade de vida e para o controle clínico de portadores de DRC em tratamento conservador

Pathways to, and use of, sexual healthcare among Black Caribbean sexual health clinic attendees in England: evidence from cross-sectional bio-behavioural surveys.

BACKGROUND: In England, people of Black Caribbean (BC) ethnicity are disproportionately affected by sexually transmitted infections (STI). We examined whether differences in sexual healthcare behaviours contribute to these inequalities. METHODS: We purposively selected 16 sexual health clinics across England with high proportions of attendees of BC ethnicity. During May-September 2016, attendees at these clinics (of all ethnicities) completed an online survey that collected data on health service use and sexual behaviour. We individually linked these data to routinely-collected surveillance data. We then used multivariable logistic regression to compare reported behaviours among BC and White British/Irish (WBI) attendees (n = 627, n = 1411 respectively) separately for women and men, and to make comparisons by gender within these ethnic groups. RESULTS: BC women's sexual health clinic attendances were more commonly related to recent bacterial STI diagnoses, compared to WBI women's attendances (adjusted odds ratio, AOR 3.54, 95% CI 1.45-8.64, p = 0.009; no gender difference among BC attendees), while BC men were more likely than WBI men (and BC women) to report attending because of a partner's symptoms or diagnosis (AOR 1.82, 95% CI 1.14-2.90; AOR BC men compared with BC women: 4.36, 95% CI 1.42-13.34, p = 0.014). Among symptomatic attendees, BC women were less likely than WBI women to report care-seeking elsewhere before attending the sexual health clinic (AOR 0.60, 95% CI 0.38-0.97, p = 0.039). No ethnic differences, or gender differences among BC attendees, were observed in symptom duration, or reporting sex whilst symptomatic. Among those reporting previous diagnoses with or treatment for bacterial STI, no differences were observed in partner notification. CONCLUSIONS: Differences in STI diagnosis rates observed between BC and WBI ethnic groups were not explained by the few ethnic differences which we identified in sexual healthcare-seeking and use. As changes take place in service delivery, prompt clinic access must be maintained - and indeed facilitated - for those at greatest risk of STI, regardless of ethnicity