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BACKGROUND: Sixty-five percent of people with severe asthma and a fractional exhaled nitric oxide (Feno) greater than or equal to 45 parts per billion (ppb) are nonadherent to inhaled corticosteroids (ICSs). Digital devices recording both time of use and inhaler technique identify nonadherence and ICS responsiveness but are not widely available. As the NEXThaler dose counter activates only at an inspiratory flow rate of 35 L/min, this may provide an alternative to identifying ICS responsiveness. OBJECTIVE: To assess ICS adherence and responsiveness in severe asthma using beclometasone/formoterol (200/6 µg) NEXThaler (BFN) dose-counting. METHODS: Patients with severe asthma with a Feno greater than or equal to 45 ppb were invited to use BFN in place of their usual ICS/long-acting ß2-agonist. Feno, 6-item Asthma Control Questionnaire score, lung function, and blood eosinophil count were monitored for 3 months. A log10ΔFeno of greater than or equal to 0.24 was used to define Feno suppression as the primary marker of ICS responsiveness at day 28. RESULTS: Twenty-seven of 48 (56%) patients demonstrated significant Feno suppression at month 1 (median pre-114, post-48 ppb, P < .001). A small but significant reduction occurred in Feno nonsuppressors. The 6-item Asthma Control Questionnaire score fell a median 1.2 units in Feno suppressors (P < .001) and 0.5 units in nonsuppressors (P = .025). These effects were sustained until month 3 in Feno suppressors, with a significant improvement in FEV1 and blood eosinophils. Sixty-seven percent (18 of 27) of those with baseline ICS/long-acting ß2-agonist prescription refills of 80% or more were Feno suppressors, suggesting prior nonadherence despite adequate prescription collection. Seventy-nine percent of Feno suppressors did not require biologics within mean 11.4 months from initial dose counting. CONCLUSIONS: BFN dose-counting identifies ICS responsiveness in severe asthma with the implication that these patients may not need to progress to biological therapies.
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Antiasmáticos , Asma , Beclometasona , Fumarato de Formoterol , Óxido Nítrico , Humanos , Asma/tratamento farmacológico , Masculino , Fumarato de Formoterol/administração & dosagem , Fumarato de Formoterol/uso terapêutico , Feminino , Beclometasona/administração & dosagem , Beclometasona/uso terapêutico , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico/análise , Adulto , Administração por Inalação , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Adesão à Medicação , Etanolaminas/uso terapêutico , Etanolaminas/administração & dosagem , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Idoso , Combinação de Medicamentos , Resultado do Tratamento , Eosinófilos/imunologia , Testes de Função RespiratóriaRESUMO
The number of ground-nesting ducks in the wetlands of Great Salt Lake, Utah has drastically decreased in the past few decades. A potential cause for this decline is the increase of predator species and their abundances, which has caused most nests to fail from depredation. Ground-nesting ducks may be able to reduce the risk of nest depredation by selecting nest sites where local physical structures or vegetation provides olfactory or visual concealment. To test this, we used logistic exposure models to look at the effect of nest-site characteristics on daily survival rates (DSRs) of nests during 2019, 2020, and 2021 in the wetlands of Great Salt Lake, Utah. We found 825 duck nests including 458 cinnamon teal (Spatula cyanoptera), 166 mallards (Anas platyrhynchos), and 201 gadwalls (Mareca strepera). DSRs were 0.9714 ± 0.0019 in 2019, 0.9282 ± 0.0049 in 2020, and 0.8274 ± 0.0185 in 2021. Survival rates varied among years but not among duck species. Striped skunks (Mephitis mephitis) and raccoons (Procyon lotor) were responsible for 85% of depredated nests. Nests located near other duck nests had higher DSRs than more dispersed nests. Neither visual nor olfactory characteristics correlated with increased DSRs based on AICc analysis. Nests located inside a mixed nesting colony of American avocets (Recurvirostra americana), black-necked stilts (Himantopus mexicanus), and common terns (Sterna hirundo) had higher DSRs than duck nests outside the colony. Increased nesting densities of ducks and other colonial waterbirds had the greatest impact on nesting success. Increased nest density may be encouraged through early spring green-up.
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Chronic hepatitis B (CHB) most commonly occurs following infection in early childhood. Prevalence varies markedly around the globe. Country of birth is therefore a strong predictor of CHB risk in adults. We used country of birth census data to predict CHB risk and carry out geographically targeted screening in East Yorkshire, UK. Despite engaging individuals born in high-prevalence countries with testing, we observed lower than expected prevalence in targeted highest-risk areas, which may indicate barriers to testing for people with undiagnosed CHB. Improved strategies for engagement with high-risk groups will be key for viral hepatitis elimination.
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Hepatite B Crônica , Hepatite B , Adulto , Humanos , Pré-Escolar , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Projetos Piloto , Infecção Persistente , Prevalência , Reino Unido/epidemiologiaRESUMO
The UK Government Web Archive (UKGWA) has been archiving government websites since 1996 and now holds regular snapshots of over 5000 sites. Currently, this material can be accessed through browsing or a simple keyword search interface on their website and has also been catalogued in The National Archives' online catalogue, Discovery. However, the scale of the UKGWA exposes the limits of the current search interface, and there is no facility to understand the archive in aggregate. This article seeks to go beyond the simple keyword search by exploring the data sources available, from APIs to web crawling, for computational analysis of the UKGWA. The article is accompanied by two Python Notebooks which present examples of analysis using each data source. Notebooks lower the technical barriers for the reader to explore and interpret the UKGWA as data, while surfacing the challenges around making web material computationally accessible.
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We introduce a new chamfering paradigm, locally connecting pixels to produce path distances that approximate Euclidean space by building a small network (a replacement product) inside each pixel. These " RE -grid graphs" maintain near-Euclidean polygonal distance contours even in noisy data sets, making them useful tools for approximation when exact numerical solutions are unobtainable or impractical. The RE -grid graph creates a modular global architecture with lower pixel-to-pixel valency and simplified topology at the cost of increased computational complexity due to its internal structure. We present an introduction to chamfering replacement products with a number of case study examples to demonstrate the potential of these graphs for path-finding in high frequency and low resolution image spaces which motivate further study. Possible future applications include morphology, watershed segmentation, halftoning, neural network design, anisotropic image processing, image skeletonization, dendritic shaping, and cellular automata.
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OBJECTIVES: Examine the patterns of cigarette smoking and e-cigarette use (vaping), the perceived harm of e-cigarettes compared with tobacco cigarettes, and associations between smoking and vaping with student characteristics. DESIGN: Cross-sectional studies. SETTING: The University of Queensland (UQ), Australia and eight New Zealand (NZ) universities. PARTICIPANTS: Students at UQ: 4957 (70.8% aged <25 years, 63.0% women) and NZ: 1854 (82.5% aged <25 years, 60.1% women). METHODS: Χ2 tests compared smoking by age and gender, and vaping by age, gender and smoking status. Two-sided p<0.05 was considered significant and 95% CIs reported where appropriate. Multinomial logistic regression examined associations between smoking and vaping (exclusive smoking, exclusive vaping, dual use and non-use) with age, gender and student type (domestic vs international). RESULTS: Smoking (UQ vs NZ, 95% CI): ever 45.2% (43.8% to 46.6%) vs 50.0% (47.7% to 52.3%), current 8.9% (8.1% to 9.7%) vs 10.4% (9.1% to 11.9%) and daily 5.2% (4.6% to 5.8%) vs 5.6% (4.6% to 6.7%), and not smoking in indoor 98.3% vs 87.7% or outdoor smoke-free spaces 83.8% vs 65.3%.Vaping (UQ vs NZ, 95% CI): ever 20.9% (19.8% to 22.1%) vs 37.6% (35.4% to 39.9%), current 1.8% (1.5% to 2.2%) vs 6.5% (5.4% to 7.7%) and daily 0.7% (0.5% to 1.0%) vs 2.5% (1.9% to 3.4%), and not vaping in indoor 91.4% vs 79.6% or outdoor smoke-free spaces 84.4% vs 71.3%. Of respondents, 71.7% (70.3% to 73.2%) vs 75.3% (72.9% to 77.6%) perceived e-cigarettes as less harmful than tobacco cigarettes.Men were more likely than women to smoke and vape, and to believe that e-cigarettes are less harmful. Regression models containing all predictors for smoking and vaping were significant and the effect of gender was significant for dual use, exclusive smoking and exclusive vaping (all p<0.01). Men had higher odds for smoking, vaping or dual use. CONCLUSIONS: Results suggest significant differences in patterns of smoking and vaping of university students in Australia and NZ, and a strong influence of gender on smoking and vaping.
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Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Nova Zelândia/epidemiologia , Queensland/epidemiologia , Estudantes , Inquéritos e Questionários , Nicotiana , UniversidadesRESUMO
The consequences of alcohol and other drug (AoD) use are well documented. This study investigated factors associated with having family/whanau or close friend who used AoD in harmful ways in New Zealand. Data came from a July-August 2020 cross-sectional survey of students from eight universities (n = 946). Participants were asked if they had family/whanau or close friends in New Zealand who consumed alcohol or used other drugs (cannabis, ecstasy/MDMA, methamphetamine, cocaine, heroin, prescription drugs, inhalants, or other) in a way that negatively impacted them, their family, or close friends in the last 12 months. Logistic regression assessed associations of having family/whanau or close friend who used AoD harmfully with student characteristics. Of respondents, 36.2% (33.1-39.4) had family/whanau or close friend who had consumed alcohol harmfully, and 42.9% (39.5-46.3) had family/whanau or close friend who had used at least one drug harmfully. Respondents' age and ethnicity were significantly associated with having family/whanau or close friend who used AoD harmfully. The results suggest widespread harmful AoD use and potentially significant second-hand effects of AoD use in New Zealand. These data can be used to supplement information from traditional in-person surveys of individuals using alcohol and other drug (e.g., the New Zealand Health Survey).
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Preparações Farmacêuticas , Transtornos Relacionados ao Uso de Substâncias , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Amigos , Humanos , Nova Zelândia/epidemiologia , Estudantes , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , UniversidadesRESUMO
OBJECTIVE: Data on associations of history of mental illness (HMI) with smoking and vaping in New Zealand (NZ) are lacking. This study examines these associations in university students aged 18-24 years. METHODS: Data came from a 2018 national cross-sectional study of university students and included information on demographic characteristics, smoking, vaping and participant health in the previous 12-months. χ2 tests compared patterns of smoking and vaping, and logistic regression assessed associations of HMI with smoking and vaping, controlling for age, gender and ethnicity. An HMI was defined as a diagnosis/treatment for depression, anxiety/nervous disorder, or other mental health condition in the previous 12-months. RESULTS: The sample comprised 1293 students: 61.3% aged 18-20; 62.8% female; 7.8% Maori, 92.2% non-Maori, and 18.5% reported an HMI. Smoking: 49.7% (95% CI 47.0-52.5) reported ever, 10.5% (8.9-12.3) current and 5.0% (3.9-6.4) daily smoking. Vaping: 38.7% (36.0-41.4) reported ever, 6.3% (5.1-7.8) current and 1.9% (1.3-2.8) daily vaping. Participants with HMI were significantly more likely to smoke: ever (64.9% vs 46.3%, p < .001), current (15.1% vs 9.5%, p = .011) and daily (7.5% vs 4.5%, p = .050), and vape: ever (49.4% vs 36.3%, p < .001) and current (9.2% vs 5.7%, p = .044) than participants without HMI. The model containing all predictors of HMI was significant, χ2 (5, N = 1293) = 24.09, p < .001. Gender (OR 0.54, (0.4-0.75)), current smoking (OR 1.82, (1.19-2.78)) and current vaping (OR 1.73, (1.02-2.93)) made unique significant contributions to the model. CONCLUSIONS: The prevalence of smoking and vaping were significantly higher in students with HMI, and there were strong associations between HMI and smoking and vaping.
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Sistemas Eletrônicos de Liberação de Nicotina , Transtornos Mentais , Vaping , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Nova Zelândia/epidemiologia , Fumar/epidemiologia , Estudantes , Universidades , Adulto JovemRESUMO
OBJECTIVE: In March 2011, New Zealand (NZ) launched an aspirational goal to reduce smoking prevalence to 5% or less by 2025 (Smokefree 2025 goal). Little is known about university students' awareness of, support for and perceptions about this goal. We sought to narrow the knowledge gap. SETTING: University students in NZ. METHODS: We analysed data from a 2018 cross-sectional survey of university students across NZ. Logistic regression analysis examined the associations between responses about the Smokefree goal with smoking and vaping, while controlling for age, sex and ethnicity. Confidence intervals (95% CI) were reported where appropriate. PARTICIPANTS: The sample comprised 1476 students: 919 (62.3%) aged 18 to 20 and 557 (37.7%) aged 21 to 24 years; 569 (38.6%) male and 907 (61.4%) female; 117 (7.9%) Maori and 1359 (92.1%) non-Maori. Of these, 10.5% currently smoked (ie, smoked at least monthly) and 6.1% currently vaped (ie, used an e-cigarette or vaped at least once a month). RESULTS: Overall awareness of the Smokefree goal was 47.5% (95% CI: 44.9 to 50.1); support 96.9% (95% CI: 95.8 to 97.8); belief that it can be achieved 88.8% (95% CI: 86.8 to 90.7) and belief that e-cigarettes/vaping can help achieve it 88.1% (95% CI: 86.0 to 89.9).Dual users of tobacco cigarettes and e-cigarettes had greater odds of being aware of the Smokefree goal (OR=3.07, 95% CI: 1.19 to 7.92), current smokers had lower odds of supporting it (OR=0.13, 95% CI: 0.06 to 0.27) and of believing that it can be achieved (OR=0.15, 95% CI: 0.09 to 0.24) and current vapers had greater odds of believing that e-cigarettes/vaping can help to achieve it (OR=8.57, 95% CI: 1.18 to 62.52) compared with non-users. CONCLUSIONS: The results suggest strong overall support for the Smokefree goal and belief that it can be achieved and that e-cigarettes/vaping can help achieve it. Smoking and vaping were associated with high awareness of the Smokefree goal, but lower support and optimism that it can be achieved.
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Sistemas Eletrônicos de Liberação de Nicotina , Fumar , Vaping , Adolescente , Atitude , Estudos Transversais , Feminino , Objetivos , Governo , Humanos , Masculino , Nova Zelândia/epidemiologia , Fumar/epidemiologia , Estudantes , Universidades , Adulto JovemRESUMO
OBJECTIVES: To examine electronic cigarette use, reasons for use and perceptions of harm among university students. DESIGN: Cross-sectional study. SETTING: University students across New Zealand. METHODS: We analysed data from a 2018 cross-sectional survey of university students, weighted to account for undersampling and oversampling by gender and university size. χ2 tests were used to compare e-cigarette use, reasons for use and perceptions of harm by age, gender, ethnicity and cigarette smoking. PARTICIPANTS: The sample comprised 1476 students: 62.3% aged 18-20 years, 37.7% aged 21-24 years; 38.6% male, 61.4% female; 7.9% Maori and 92.1% non-Maori. RESULTS: 40.5% of respondents (95% CI 37.9 to 43.1) reported ever, 6.1% (4.9-7.4) current and 1.7% (1.1-2.5) daily use. Regardless of frequency, 11.5% of vapers had vaped daily for ≥1 month, 70.2% of whom used nicotine-containing devices; 80.8% reported not vaping in indoor and 73.8% in outdoor smoke-free spaces. Among ever vapers, curiosity (67.4%), enjoyment (14.4%) and quitting (2.4%) were common reasons for vaping. 76.1% (73.4-78.7) of respondents believed e-cigarettes were less harmful than cigarettes.More males than females reported vaping (ever, current, daily and daily for ≥1 month), nicotine use and belief that e-cigarettes were less harmful than cigarettes. More participants aged 18-20 years reported not vaping in outdoor smoke-free spaces, vaping out of curiosity and belief that e-cigarettes were less harmful than cigarettes, while more participants aged 21-24 years vaped daily for ≥1 month and for enjoyment. More Maori than non-Maori ever vaped. More cigarette smokers than non-smokers vaped (ever, current, daily and daily for ≥1 month), used nicotine and vaped to quit, while more non-smokers did not vape in smoke-free spaces and vaped out of curiosity. CONCLUSIONS: Our results suggest high prevalence of e-cigarette ever and current use, particularly among males and smokers. Many vaped out of curiosity and perceived e-cigarettes as less harmful than cigarettes.
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Sistemas Eletrônicos de Liberação de Nicotina , Comportamentos Relacionados com a Saúde , Estudantes , Vaping/epidemiologia , Adolescente , Estudos Transversais , Etnicidade , Feminino , Humanos , Masculino , Nova Zelândia/epidemiologia , Universidades , Vaping/etnologia , Adulto JovemRESUMO
OBJECTIVES: Although the smoking prevalence continues to decline in New Zealand (NZ) overall, little is known about smoking in university students. A 2013 survey of students aged 17-25 years found that 14% were current smokers, and 3% daily smokers. However, the sample did not include students from all NZ universities. This study examines the prevalence and patterns of cigarette smoking among students aged 18-24 years. SETTING: University students across NZ. METHODS: Data came from a March to May 2018 survey of students from all NZ universities, and were weighted to account for undersampling and oversampling, based on gender and university size. χ2 tests were used to compare smoking by age, gender and ethnicity. PARTICIPANTS: 1476 participants were included: 919 (62.3%) aged 18-20 years and 557 (37.7%) aged 21-24 years; 569 (38.6%) male and 907 (61.4%) female; and 117 (7.9%) Maori and 1359 (92.1%) non-Maori. RESULTS: 49.8% (95% CI 47.2 to 52.4) of respondents reported ever smoking, 11.1% (95% CI 9.5 to 12.9) currently smoked (smoked at least once a month) and 5.9% (95% CI 4.8 to 7.3) smoked at least daily (daily smokers). Of current smokers, 63.6% smoked 1-5 cigarettes/day, 45.8% smoked daily, 73.4% smoked first cigarette >60 min after waking, 86.0% never/almost never smoked in indoor and 64.6% in outdoor smokefree spaces, 69.9% planned to quit and 32.4% had tried to quit. Ever, current and daily smoking were significantly higher in 21-24 compared with 18-20 years olds, and in males compared with females. Older participants were more likely to report smoking more cigarettes/day. Maori were more likely to report ever smoking than non-Maori. CONCLUSIONS: Current smoking among NZ university students aged 18-24 years appears to be declining but daily smoking could be increasing. However, many students appeared less addicted to nicotine, and willing to quit. We recommend increasing the availability of smokefree services for students who wish to quit.
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Fumar Cigarros/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Fumar Cigarros/etnologia , Estudos Transversais , Feminino , Humanos , Masculino , Nova Zelândia/epidemiologia , Prevalência , Distribuição por Sexo , Inquéritos e Questionários , Universidades/estatística & dados numéricos , Adulto JovemRESUMO
This article aims to provide an overview of drug discovery with a focus on application within dermatology. The term "drug" can be used to describe a wide variety of agents, including small molecules, cell therapies, and antibodies, which may be dosed intravenously, orally, topically, or by other routes of administration. We summarize the economics and risks involved in drug discovery. Understanding the needs of patients and clinicians through use of a target product profile before initiating drug discovery can reduce time and effort spent developing a poor or unneeded drug. For small molecule drug discovery, a chemical starting point is then required. We present four options for finding a chemical starting point for drug discovery projects: screening libraries of compounds or modifying, reformulating, or repositioning a known drug. Examples of each technique's use in dermatology are provided. We also describe the subsequent steps involved in discovery of a new drug. To help interested readers, we provide information on how to engage with academic drug discovery centers or industrial partners.
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Custos e Análise de Custo , Descoberta de Drogas/métodos , Animais , Ensaios Clínicos como Assunto , Descoberta de Drogas/economia , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Risco , Estados Unidos , United States Food and Drug AdministrationRESUMO
In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, which can complicate interpretation of the observed effects. We set out to design soft drug S1PR modulators as topical tool compounds to overcome this limitation. A fast follower approach starting from the drug ponesimod allowed the rapid development of an active phenolic series of soft drugs. The phenols were, however, chemically unstable. Protecting the phenol as an ester removed the instability and provided a compound that is converted by enzymatic hydrolysis in the skin to the phenolic soft drug species. In simple formulations, topical dosing of these S1PR modulators to mice led to micromolar skin concentrations but no detectable blood concentrations. These topical tools will allow researchers to investigate the role of S1PR in skin, without involvement of systemic S1PR biology.
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We describe an algorithm to compute trisections of orientable four-manifolds using arbitrary triangulations as input. This results in explicit complexity bounds for the trisection genus of a 4-manifold in terms of the number of pentachora (4-simplices) in a triangulation.
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The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clinical trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index. By modifying ponesimod, we discovered an ester series of S1PR agonists. To increase metabolic instability in plasma we synthesised esters described as specific substrates for paraoxonase and butyrylcholinesterases, esterases present in human plasma.
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Descoberta de Drogas , Receptores de Lisoesfingolipídeo/efeitos dos fármacos , Tiazóis/farmacologia , Administração Tópica , Arildialquilfosfatase/sangue , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Esterases/sangue , Esterases/metabolismo , Humanos , Pele/enzimologia , Solubilidade , Receptores de Esfingosina-1-Fosfato , Relação Estrutura-Atividade , Tiazóis/administração & dosagemRESUMO
The successful remediation of clinicians demonstrating poor performance in the workplace is essential to ensure the provision of safe patient care. Clinicians may develop performance problems for numerous reasons, including health, personal factors, the workplace environment, or outdated knowledge/skills. Performance problems are often complex involving multifactorial issues, encompassing knowledge, skills, and professional behaviors. It is important that (where possible and appropriate) clinicians are supported through effective remediation to return them to safe clinical practice. A review of the literature demonstrated that research into remediation is in its infancy, with little known about the effectiveness of remediation programs currently. Current strategies for the development of remediation programs are mostly "intuitive"; a few draw upon established theories to inform their approach. Similarly, although it has been established that identification of the nature/scope of performance problems through assessment is an essential first step within remediation, the need for a more widespread "diagnosis" of why the problems exist is emerging. These reasons for poor performance, particularly in the context of experienced practicing clinicians, are likely to have an impact on the potential success of remediation and should be considered within the "diagnosis." A new model for diagnosing the performance problems of the clinicians has been developed, using behavioral change theories to explore known barriers to successful remediation, such as insight, motivation, attitude, self-efficacy, and the working environment, in addition to addressing known deficits regarding knowledge and skills. This novel approach is described in this article. An initial feasibility study has demonstrated the acceptability and practical implementation of our model.
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Competência Clínica/normas , Pessoal de Saúde/educação , Ensino de Recuperação/métodos , Desempenho Profissional/normas , Terapia Comportamental/métodos , Humanos , Modelos Educacionais , Motivação , Ensino de Recuperação/normas , Desenvolvimento de Pessoal/métodosRESUMO
Tobacco smoking is common among people with mental illnesses, and they carry a higher burden of smoking-related illnesses. Despite this, smoke-free policies and systems for supporting cessation have proved difficult to introduce in mental health and drug and alcohol services (MHDAS). This paper examines the barriers to becoming smoke free within New Zealand services. Key informants, including staff, smoke-free coordinators, and cessation specialists were interviewed. Of the 142 invited informants 61 agreed (42%) to participate in a telephone interview, and 56 provided useable data. Organizations had a permissive or transitioning smoking culture, or were smoke free, defined by smoke-free environments, smoke-free-promoting attitudes and behaviours of management and staff, and cessation support. Most organizations were on a continuum between permissive and transitional cultures. Only eight services had a fully smoke-free culture. MHDAS face many challenges in the transition to a smoke-free culture. They are not helped by exemptions in smoke-free policies for mental health services, staff smoking, negative staff attitudes to becoming smoke free, poor knowledge of nicotine dependence, smoking-related harm and comorbidities, and poor knowledge and skills regarding cessation-support options. Health inequalities will continue across both service and socioeconomic divides without a concerted effort to address smoking.
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Alcoolismo/enfermagem , Atitude do Pessoal de Saúde , Implementação de Plano de Saúde , Política Antifumo , Abandono do Hábito de Fumar/psicologia , Centros de Tratamento de Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/enfermagem , Adulto , Alcoolismo/psicologia , Comportamento Cooperativo , Coleta de Dados , Feminino , Humanos , Comunicação Interdisciplinar , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Since the dawn of time, or at least the dawn of recombinant DNA technology (which for many of today's scientists is the same thing), investigators have been cloning and expressing heterologous proteins in a variety of different cells for a variety of different reasons. These range from cell biological studies looking at protein-protein interactions, post-translational modifications, and regulation, to laboratory-scale production in support of biochemical, biophysical, and structural studies, to large scale production of potential biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate microscale purification (pull-downs), protein visualization (epitope tags), enhanced expression and solubility (protein partners, e.g., GST, MBP, TRX, and SUMO), and generic purification (e.g., His-tags, streptag, and FLAG™-tag). Frequently, these latter two goals are combined in a single fusion partner. In this review, we examine the most commonly used fusion methodologies from the perspective of the ultimate use of the tagged protein. That is, what are the most commonly used fusion partners for pull-downs, for structural studies, for production of active proteins, or for large-scale purification? What are the advantages and limitations of each? This review is not meant to be exhaustive and the approach undoubtedly reflects the experiences and interests of the authors. For the sake of brevity, we have largely ignored epitope tags although they receive wide use in cell biology for immunopreciptation.
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Clonagem Molecular/métodos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Animais , Humanos , Imunoprecipitação , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Processamento de Proteína Pós-Traducional , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/isolamento & purificação , SolubilidadeRESUMO
Detailed kinetic and computational investigation of the enantio- and diastereoselective allylation of aldehydes 1 with allyltrichlorosilanes 5, employing the pyridine N-oxides METHOX (9) and QUINOX (10) as chiral organocatalysts, indicate that the reaction can proceed through a dissociative (cationic) or associative (neutral) mechanism: METHOX apparently favors a pentacoordinate cationic transition state, while the less sterically demanding QUINOX is likely to operate via a hexacoordinate neutral complex. In both pathways, only one molecule of the catalyst is involved in the rate- and selectivity-determining step, which is supported by both experimental and computational data.
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AIM: The aim of the present study was to provide up-to-date descriptive information in relation to youth (15-24 years) with type 1 diabetes, residing within the Canterbury District Health Board (CDHB) catchment area. This included calculating the prevalence of type 1 diabetes in youth, and investigating whether there was an increase in the prevalence since a previous study reporting the prevalence of type 1 diabetes in youth in the CDHB in 2003. METHODS: Data were collected from multiple clinical and research sources. Descriptive information and demographic characteristics, including age, gender, ethnicity, deprivation level, and diabetes duration were gathered. The prevalence, stratified by age and ethnicity, was calculated using the 2006 population census data. RESULTS: There were 248 people with type 1 diabetes aged between 15 and 24 years residing within the CDHB area at the time of present study, giving a prevalence of 426 per 100,000 European youth with type 1 diabetes. The prevalence is found to have increased by 45 per 100,000 (12%) since 2003, but was statistically insignificant. CONCLUSIONS: There was no statistically significant increase in the prevalence of type 1 diabetes in youth in the CDHB catchment area between 2003 and 2010. However, the absolute figures of adolescents and young adults with type 1 diabetes have increased, which implies an increased demand on health care associated with diabetes compared to 7 years ago.