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1.
Nature ; 608(7922): 275-286, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948707

RESUMO

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied.


Assuntos
Modelos Climáticos , Aquecimento Global , Camada de Gelo , Temperatura , Regiões Antárticas , Previsões , Aquecimento Global/história , Aquecimento Global/prevenção & controle , Aquecimento Global/estatística & dados numéricos , História do Século XXI , Elevação do Nível do Mar/história , Elevação do Nível do Mar/estatística & dados numéricos
2.
PLoS Biol ; 20(6): e3001626, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35658016

RESUMO

The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.


Assuntos
Evolução Biológica , Microbiota , Genótipo , Mutação , Fenótipo
3.
Aust J Rural Health ; 32(3): 547-553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38511481

RESUMO

OBJECTIVE: To establish prevalence and associations of provision of nursing home visits (NHV) and home visits (HV) by early-career specialist GPs. Of particular interest were associations of rurality with performing NHVs and HVs. METHODS: A cross-sectional study. DESIGN: A questionnaire-based study. SETTING: Australian general practice. PARTICIPANTS: Early-career specialist GPs, practising in Australia, who attained Fellowship between January 2016 and July 2018, inclusive, having completed GP training in NSW, the ACT, Eastern Victoria or Tasmania. MAIN OUTCOME MEASURES: Current provision of NHV and HV. RESULTS: NHV were provided by 34% of participants (59% in rural areas) and HV by 41% of participants (60% in rural areas). Remote, rural or regional practice location, as compared to major-city practice, was strongly associated with performing NHV as an early-career specialist GP; multivariable OR 5.87 (95% CI: 2.73, 12.6), p < 0.001, and with the provision of HV; multivariable OR 3.64 (95% CI: 1.63, 8.11), p = 0.002. Rurality of GP training (prior to attaining Fellowship) was significantly univariably associated with providing NHV and with providing HV as an early-career specialist GP. On multivariable analyses, these were no longer statistically significant. CONCLUSION: Early-career specialist GPs located in regional/remote areas are more likely than their urban colleagues to provide NHV and HV.


Assuntos
Clínicos Gerais , Visita Domiciliar , Casas de Saúde , Humanos , Estudos Transversais , Feminino , Masculino , Casas de Saúde/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Visita Domiciliar/estatística & dados numéricos , Inquéritos e Questionários , Prevalência , Serviços de Saúde Rural/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Austrália , Tasmânia
4.
Aust J Rural Health ; 31(5): 906-913, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37488936

RESUMO

INTRODUCTION: Access to after-hours care (AHC) is an important aspect of general practice service provision. OBJECTIVE: To establish the prevalence and associations of early-career GPs' provision of AHC. DESIGN: An analysis of data from the New alumni Experiences of Training and independent Unsupervised Practice (NEXT-UP) cross-sectional questionnaire-based study. Participants were early-career GPs (6-month to 2-year post-Fellowship) following the completion of GP vocational training in NSW, the ACT, Victoria or Tasmania. The outcome factor was 'current provision of after-hours care'. Associations of the outcome were established using multivariable logistic regression. FINDINGS: Three hundred and fifty-four early-career GPs participated (response rate 28%). Of these, 322 had responses available for analysis of currently performing AHC. Of these observations, 128 (40%) reported current provision of AHC (55% of rural participants and 32% of urban participants). On multivariable analysis, participants who provided any AHC during training were more likely to be providing AHC (odds ratio (OR) 5.51, [95% confidence interval (CI) 2.80-10.80], p < 0.001). Current rural location and in-training rural experience were strongly associated with currently providing AHC in univariable but not multivariable analysis. DISCUSSION: Early-career GPs who provided AHC during training, compared with those who did not, were more than five times more likely to provide after-hours care in their first 2 years after gaining Fellowship, suggesting participation in AHC during training may have a role in preparing registrars to provide AHC as independent practitioners. CONCLUSION: These findings may inform future GP vocational training policy and practice concerning registrars' provision of AHC during training.


Assuntos
Plantão Médico , Medicina Geral , Clínicos Gerais , Humanos , Prevalência , Estudos Transversais , Austrália , Medicina Geral/educação
5.
Educ Prim Care ; 34(2): 74-82, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36851829

RESUMO

PURPOSE: To evaluate Australian early-career general practitioners' perceptions of the utility of their prior vocational training in preparing them for independent specialist practice. We hypothesised that in-practice teaching would be perceived as more useful than formal education delivered by Regional Training Organisations (RTOs). METHODS AND MATERIALS: A cross-sectional questionnaire-based study of early-career general practitioners (RTO 'alumni'). The outcomes were Likert scale ratings of alumni's perceived impact of RTO education versus in-practice training on their preparedness for independent practice. Ratings were compared using Wilcoxon signed-rank tests. Multivariable linear regression was used to establish alumni characteristics associated with perceptions of utility of in-practice versus RTO-delivered education. RESULTS: Three hundred and fifty-four alumni responded (response rate 28%). In-practice training was rated statistically significantly higher than RTO education for minor procedural skills, teaching skills, professional responsibilities, tolerating clinical uncertainty, and preparing for managing child and adolescent health, aged care, chronic disease, multi-morbidity and mental health. RTO education rated higher than in-practice training for practising evidence-based medicine and Aboriginal and Torres Strait Islander health. For a number of further areas, there was no statistically significant difference in alumni ratings of utility. CONCLUSIONS: In-practice or RTO-led teaching was perceived as more useful for some components of independent practice, whilst for others there was no significant difference. The findings support recognition of the individual educational components of a blended education/training structure.


Assuntos
Medicina Geral , Clínicos Gerais , Criança , Humanos , Adolescente , Idoso , Clínicos Gerais/educação , Educação Vocacional , Austrália , Estudos Transversais , Tomada de Decisão Clínica , Incerteza , Medicina Geral/educação
6.
Educ Prim Care ; 34(5-6): 244-253, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671661

RESUMO

While GPs are working fewer clinical hours and many GP trainees (registrars) do not foresee themselves working full-time in clinical practice, little is known of the epidemiology of registrars training part-time. We aimed to establish the prevalence of general practice part-time training (PTT), and part-time registrars' characteristics and practice patterns. A cross-sectional analysis was conducted of data from the Registrar Clinical Encounters in Training project, an ongoing cohort study of Australian GP registrars' clinical experiences over 60 consecutive consultations in each of three training terms. Univariable and multivariable logistic regression analyses were conducted with the outcome 'training part-time'. 1790 registrars contributed data for 4,135 registrar-terms and 241,945 clinical encounters. Nine hundred and twenty-two registrar-terms (22%, 95%CI:21%-24%) and 52,339 clinical encounters (22%, 95%CI:21%-22%) involved PTT. Factors associated with PTT were registrar characteristics - female gender, older age, in a later training stage, performing other regular medical work; practice characteristics - working in a higher socioeconomic status area; and patient characteristics - seeing more patients new to the registrar and seeing more patients from a non-English-speaking background. No consultation or consultation action factors were significantly associated with PTT. Registrars, practices, and patient associations have GP training implications. The lack of registrar consultation or consultation action associations suggests there may be limited impact of PTT on patient care.


Assuntos
Medicina Geral , Clínicos Gerais , Humanos , Feminino , Estudos Transversais , Estudos de Coortes , Prevalência , Austrália , Medicina Geral/educação , Clínicos Gerais/educação , Padrões de Prática Médica
7.
Exp Eye Res ; 221: 109132, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35636488

RESUMO

The distal outflow pathway of the human eye consists of the outer wall of Schlemm's canal, collector channels, and the deep-scleral, mid-scleral and episcleral vessels. It is the last region of transit for aqueous humor before returning to the venous system. While the trabecular meshwork, scleral spur, and inner wall of Schlemm's canal have been extensively analyzed to define their contributions to aqueous outflow, the role of the distal outflow pathway is not completely understood. Collector channels, emanating from Schlemm's canal were previously thought to be passive conduits for aqueous humor. However, recent studies have shown many collector channels contain flap-like appendages which move with changes in pressure. These findings, along with studies demonstrating innervation of episcleral vessels, have led to questions regarding whether other structures in the distal outflow pathway are under neural regulation and how this may influence aqueous humor outflow. This study evaluates the innervation of the outer wall of Schlemm's canal and collector channels, along with the deep-scleral, mid-scleral and episcleral vasculature with microcomputed tomography and 3-dimensional reconstruction, correlative light microscopy, immunohistochemistry, and transmission electron microscopy. Peripheral, autonomic, and sensory nerve fibers were found to be present adjacent to Schlemm's canal outer wall endothelium, collector channel endothelium, and in the different regions of the distal outflow vasculature. Nerves were more commonly identified in regions that contained collector channels when compared to regions without collector channels. These findings regarding the neural anatomy suggest an active neural regulation of aqueous humor outflow throughout the proximal and distal regions of the conventional outflow pathway.


Assuntos
Esclera , Malha Trabecular , Humor Aquoso/metabolismo , Humanos , Pressão Intraocular , Microscopia Eletrônica de Transmissão , Esclera/irrigação sanguínea , Malha Trabecular/metabolismo , Microtomografia por Raio-X
8.
Entropy (Basel) ; 25(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36673200

RESUMO

Decentralized finance (DeFi) is by far the most popular application of blockchain technology. Despite the wide acceptance of new financial instruments and services, there are still many unexplored areas in the field. We dedicate this research to the understanding of one of the most crucial limitations of decentralized finance-oracles. DeFi protocols, as well as other blockchain applications, function in a closed environment and regularly need to fetch real-world information (e.g., assets' prices)-the tool used for this purpose is called an oracle. We review the existing oracle types in DeFi applications and focus our research on the least explored one: when another protocol, typically a decentralized exchange, serves as a price oracle. After explaining the mechanisms behind the decentralized exchanges, we introduce an algorithmic model that allows one to safely design a decentralized oracle and adjust crucial parameters. We believe that understanding and implementing the logic presented in the model can help to reduce the chances of price manipulations attacks, which are the most frequent incident types in DeFi.

9.
Crit Care Med ; 48(9): 1375-1382, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32826489

RESUMO

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and makes recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.


Assuntos
Cuidados Críticos/organização & administração , Estado Terminal , Unidades de Terapia Intensiva/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Papel Profissional , Humanos , Melhoria de Qualidade , Sociedades Médicas , Sociedades Farmacêuticas
10.
Crit Care Med ; 48(9): e813-e834, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32826496

RESUMO

OBJECTIVES: To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.


Assuntos
Cuidados Críticos/organização & administração , Estado Terminal , Unidades de Terapia Intensiva/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Papel Profissional , Melhoria de Qualidade , Sociedades Médicas , Sociedades Farmacêuticas
11.
BMC Health Serv Res ; 20(1): 834, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891144

RESUMO

BACKGROUND: In Australia registrar training to become a general practitioner (GP) involves three to four years of supervised learning with at least 50% of GP registrars training wholly in rural areas. In particular rural over regional GP placements are important for developing future GPs with broader skills because the rural scope of practice is wider. Having enough GP supervisors in smaller rural communities is essential such training. We aimed to explore what makes rural GPs' based outside of major regional centres, participate in supervising or not, their experiences of supervising, and impact of their practice context. METHODS: Semi-structured interviews were undertaken with 25 GPs based in rural Tasmania (outside of major regions - Hobart and Launceston), in towns of < 25,000 population, to explore the GPs' professional backgrounds, their experiences of supervising GP registrars, their practice context and their decisions about supervising GP registrars or not. Thematic analysis was undertaken; key ideas, concepts and experiences were identified and then reviewed and further refined to core themes. RESULTS: Supervising was perceived to positively impact on quality of clinical care, reduce busy-ness and improve patient access to primary care. It was energising for GPs working in rural contexts. Rural GPs noted business factors impacted the decision to participate in supervision and the experience of participating: including uncertainty and discontinuity of registrar supply (rotational training systems), registrar competence and generating income. CONCLUSIONS: Supervising is strongly positive for rural GPs and related to job satisfaction but increasing supervision capacity in rural areas may depend on better policies to assure continuity of rural registrars as well as policies and systems that enable viable supervision models tailored to the context.


Assuntos
Clínicos Gerais/organização & administração , Atenção Primária à Saúde/organização & administração , Serviços de Saúde Rural/organização & administração , Austrália , Feminino , Humanos , Satisfação no Emprego , Masculino , Pesquisa Qualitativa , População Rural , Tasmânia
12.
Educ Prim Care ; 31(6): 341-348, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32816649

RESUMO

The relationship between general practice (GP) registrars and their supervisors underpins the training experience for the next generation of medical practitioners. Building on recent research into the development and validation of a measure of the relationship between registrars and supervisors from the perspective of the supervisor, the current study focuses on the educational alliance from the perspective of the registrar. This paper presents an adaptation and initial validation of the clinical psychology supervisory relationship measure for GP registrars in an Australian context. Following an Expert Group review and adaptation of the items, 238 GP registrars completed the adapted tool. Using exploratory factor analysis and Procrustes confirmatory rotation, an optimal four factor model of the supervisory relationship was identified, reflecting measures of Safe base (α =.93), Supervisor investment (α =.96), Registrar professionalism (α =.90), and Emotional intelligence (α =.87). The general practice supervisory relationship measure for registrars (GP-SRMR) demonstrated excellent model fit, high internal consistency, and was theoretically consistent with the original tool. Implications for clinical education and future research are presented.


Assuntos
Clínicos Gerais/educação , Internato e Residência , Inquéritos e Questionários , Adulto , Austrália , Competência Clínica , Inteligência Emocional , Feminino , Clínicos Gerais/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Profissionalismo , Psicometria
13.
Nature ; 491(7425): 586-9, 2012 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-23086145

RESUMO

Recent estimates of Antarctica's present-day rate of ice-mass contribution to changes in sea level range from 31 gigatonnes a year (Gt yr(-1); ref. 1) to 246 Gt yr(-1) (ref. 2), a range that cannot be reconciled within formal errors. Time-varying rates of mass loss contribute to this, but substantial technique-specific systematic errors also exist. In particular, estimates of secular ice-mass change derived from Gravity Recovery and Climate Experiment (GRACE) satellite data are dominated by significant uncertainty in the accuracy of models of mass change due to glacial isostatic adjustment (GIA). Here we adopt a new model of GIA, developed from geological constraints, which produces GIA rates systematically lower than those of previous models, and an improved fit to independent uplift data. After applying the model to 99 months (from August 2002 to December 2010) of GRACE data, we estimate a continent-wide ice-mass change of -69 ± 18 Gt yr(-1) (+0.19 ± 0.05 mm yr(-1) sea-level equivalent). This is about a third to a half of the most recently published GRACE estimates, which cover a similar time period but are based on older GIA models. Plausible GIA model uncertainties, and errors relating to removing longitudinal GRACE artefacts ('destriping'), confine our estimate to the range -126 Gt yr(-1) to -29 Gt yr(-1) (0.08-0.35 mm yr(-1) sea-level equivalent). We resolve 26 independent drainage basins and find that Antarctic mass loss, and its acceleration, is concentrated in basins along the Amundsen Sea coast. Outside this region, we find that West Antarctica is nearly in balance and that East Antarctica is gaining substantial mass.


Assuntos
Gravitação , Camada de Gelo , Modelos Teóricos , Comunicações Via Satélite , Água do Mar/análise , Regiões Antárticas , Artefatos , Congelamento , Oceanos e Mares , Projetos de Pesquisa , Fatores de Tempo , Incerteza
14.
J Interprof Care ; 32(3): 274-283, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29182411

RESUMO

This article draws on data from a 5-year project that examined the effectiveness of Comprehensive primary healthcare (CPHC) in local communities. A hallmark of CPHC services is interprofessional teamwork. Drawing from this study, our article presents factors that enabled, or hindered, healthcare teams working interprofessionally in Australian primary healthcare (PHC) services. The article reports on the experiences of teams working in six Australian PHC services (four managed by state governments, one non-government sexual health organisation, and one Aboriginal community-controlled health service) during a time of significant health sector restructure. Findings are drawn from two key methods: an online survey of practitioners and managers (n = 154), and interviews with managers and practitioners (n = 60) from the six study sites. The majority of survey respondents worked with other health professionals in their service to provide interprofessional care to clients. Processes included formal team meetings, case conferencing, referring clients to other health professionals if needed, informal communication with other health professionals about clients, and team-based delivery of care. A range of interrelated factors affected interprofessional work at the services, from contextual, organisational, processual, and relational domains. Funding cuts and policy changes that saw a reorientation and re-medicalisation of South Australian services undermined interprofessional work, while a shared CPHC culture and commitment among some staff was helpful in resisting some of these effects. The co-location of services was a factor in PHC teams working interprofessionally and not only enabled some PHC teams to work more interprofessionally but also created barriers to interprofessional teamwork through disruption resulting from restructuring of services. Our study indicates the importance of decision makers taking into account the potential effects of policy and structural changes on interprofessional teamwork. Decision makers should strive to minimise unintended negative effects of changes on the functioning of interprofessional teams.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Comportamento Cooperativo , Relações Interprofissionais , Equipe de Assistência ao Paciente/organização & administração , Atenção Primária à Saúde/organização & administração , Atitude do Pessoal de Saúde , Austrália , Comunicação , Serviços de Saúde Comunitária/economia , Serviços de Saúde Comunitária/normas , Tomada de Decisões , Processos Grupais , Humanos , Liderança , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/normas , Encaminhamento e Consulta/organização & administração
15.
Proc Natl Acad Sci U S A ; 111(37): 13331-6, 2014 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-25197067

RESUMO

The roles of 2-oxoglutarate (2OG)-dependent prolyl-hydroxylases in eukaryotes include collagen stabilization, hypoxia sensing, and translational regulation. The hypoxia-inducible factor (HIF) sensing system is conserved in animals, but not in other organisms. However, bioinformatics imply that 2OG-dependent prolyl-hydroxylases (PHDs) homologous to those acting as sensing components for the HIF system in animals occur in prokaryotes. We report cellular, biochemical, and crystallographic analyses revealing that Pseudomonas prolyl-hydroxylase domain containing protein (PPHD) contain a 2OG oxygenase related in structure and function to the animal PHDs. A Pseudomonas aeruginosa PPHD knockout mutant displays impaired growth in the presence of iron chelators and increased production of the virulence factor pyocyanin. We identify elongation factor Tu (EF-Tu) as a PPHD substrate, which undergoes prolyl-4-hydroxylation on its switch I loop. A crystal structure of PPHD reveals striking similarity to human PHD2 and a Chlamydomonas reinhardtii prolyl-4-hydroxylase. A crystal structure of PPHD complexed with intact EF-Tu reveals that major conformational changes occur in both PPHD and EF-Tu, including a >20-Å movement of the EF-Tu switch I loop. Comparison of the PPHD structures with those of HIF and collagen PHDs reveals conservation in substrate recognition despite diverse biological roles and origins. The observed changes will be useful in designing new types of 2OG oxygenase inhibitors based on various conformational states, rather than active site iron chelators, which make up most reported 2OG oxygenase inhibitors. Structurally informed phylogenetic analyses suggest that the role of prolyl-hydroxylation in human hypoxia sensing has ancient origins.


Assuntos
Oxigênio/metabolismo , Fator Tu de Elongação de Peptídeos/metabolismo , Prolina/metabolismo , Pseudomonas putida/metabolismo , Chlamydomonas reinhardtii/metabolismo , Humanos , Hidroxilação , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/química , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Fator Tu de Elongação de Peptídeos/química , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Especificidade por Substrato
16.
Philos Trans A Math Phys Eng Sci ; 374(2059)2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26667913

RESUMO

Accessing and sampling subglacial environments deep beneath the Antarctic Ice Sheet presents several challenges to existing drilling technologies. With over half of the ice sheet believed to be resting on a wet bed, drilling down to this environment must conform to international agreements on environmental stewardship and protection, making clean hot-water drilling the most viable option. Such a drill, and its water recovery system, must be capable of accessing significantly greater ice depths than previous hot-water drills, and remain fully operational after connecting with the basal hydrological system. The Subglacial Lake Ellsworth (SLE) project developed a comprehensive plan for deep (greater than 3000 m) subglacial lake research, involving the design and development of a clean deep-ice hot-water drill. However, during fieldwork in December 2012 drilling was halted after a succession of equipment issues culminated in a failure to link with a subsurface cavity and abandonment of the access holes. The lessons learned from this experience are presented here. Combining knowledge gained from these lessons with experience from other hot-water drilling programmes, and recent field testing, we describe the most viable technical options and operational procedures for future clean entry into SLE and other deep subglacial access targets.

17.
Philos Trans A Math Phys Eng Sci ; 374(2059)2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26667918

RESUMO

Accumulations of sediment beneath the Antarctic Ice Sheet contain a range of physical and chemical proxies with the potential to document changes in ice sheet history and to identify and characterize life in subglacial settings. Retrieving subglacial sediments and sediment cores presents several unique challenges to existing technologies. This paper briefly reviews the history of sediment sampling in subglacial environments. It then outlines some of the technological challenges and constraints in developing the corers being used in sub-ice shelf settings (e.g. George VI Ice Shelf and Larsen Ice Shelf), under ice streams (e.g. Rutford Ice Stream), at or close to the grounding line (e.g. Whillans Ice Stream) and in subglacial lakes deep under the ice sheet (e.g. Lake Ellsworth). The key features of the corers designed to operate in each of these subglacial settings are described and illustrated together with comments on their deployment procedures.

18.
Am J Emerg Med ; 34(3): 429-32, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26778642

RESUMO

PURPOSE: Purposes of this study were to compare tibial intraosseous (TIO) and intravenous (IV) administration of vasopressin relative to return of spontaneous circulation (ROSC) and time to ROSC in an adult swine cardiac arrest model. In addition, the purposes were to compare the concentration maximum (Cmax), time to maximum concentration (Tmax), and odds of ROSC. METHODS: This was a between-subjects, prospective experimental study. Yorkshire swine (N = 21) were randomly assigned to 1 of 3 groups: TIO, IV, or control groups. The swine were anesthetized and instrumented, and then cardiac arrest was induced and sustained for 2 minutes. Cardiopulmonary resuscitation was initiated and continued for 2 minutes. Vasopressin was then administered via the TIO or IV route. Blood samples were collected for 4 minutes to determine the Cmax and Tmax of vasopressin. Concentration maximum and Tmax were calculated by use of liquid chromatography with mass spectrometry. RESULTS: There was no difference in ROSC between the TIO and IV groups (P = .63). The Cmax of vasopressin was significantly higher in the IV group compared to the TIO group (P = .017). However, there was no significant difference in ROSC, time to ROSC, or Tmax between groups (P > .05). All subjects had ROSC in both the IV and TIO groups, and none had ROSC in the control group. There was 225 times greater chance of survival for both the IV and TIO groups compared to the control group. CONCLUSION: The data support that the TIO is an effective route for vasopressin in a cardiac arrest model.


Assuntos
Parada Cardíaca/tratamento farmacológico , Vasopressinas/administração & dosagem , Vasopressinas/farmacocinética , Animais , Reanimação Cardiopulmonar , Cromatografia Líquida , Modelos Animais de Doenças , Infusões Intraósseas , Infusões Intravenosas , Espectrometria de Massas , Estudos Prospectivos , Suínos , Tíbia
19.
J Adv Nurs ; 72(9): 1991-2002, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26876765

RESUMO

AIMS: To review the key features of the nurse practitioner-client interaction in the thera-peutic encounter to inform the development of nurse practitioner-led memory clinics. BACKGROUND: Nurse practitioners spend significant time interacting with clients and their families/caregivers yet there is limited research on this interaction during therapeutic encounters in aged and primary care contexts. DESIGN: Integrative review. DATA SOURCES: Electronic search of CINAHL, Embase, Medline, PsychINFO, PubMed, Scopus, Web of Science 2004-2013; hand search of the Journal of Advanced Nursing, Journal of the American Academy of Nurse Practitioners and Journal of Clinical Nursing. REVIEW METHODS: Integrative literature review using Whittemore and Knafl's methodology. RESULTS: Ten published studies were included, representing over 900 nurse practitioners and their clients. Three key factors of nurse practitioner-client interaction were identified: nurse practitioner expertise and the influence of the therapeutic encounter context; affirming exchange as a bedrock of communication; and high levels of client engagement. In aged and primary care settings, where the therapeutic encounter requires and allows longer consultations, such as nurse practitioner-led memory clinics, patient-centred approaches can engage clients in consultations using a biopsychosocial framework, resulting in improved client satisfaction and, potentially, increased adherence to treatment plans. Nurse practitioners who are open and respectful, who encourage patients to provide more information about their lives and condition and are perceived by the client to be empathetic, are providing affirmation to the client. CONCLUSION: Affirming interactions are a key feature of successful therapeutic encounters when time and context do not allow or warrant the full repertoire of patient-centred communication.


Assuntos
Profissionais de Enfermagem , Satisfação do Paciente , Atenção Primária à Saúde , Instituições de Assistência Ambulatorial , Comunicação , Humanos
20.
Cell Tissue Bank ; 17(1): 39-50, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26361949

RESUMO

Amniotic membrane (AM) transplantation is increasingly used in ophthalmological and dermatological surgeries to promote re-epithelialization and wound healing. Biologically active cells in the epithelial and stromal layers deliver growth factors and cytokines with anti-inflammatory, anti-bacterial, anti-immunogenic and anti-fibrotic properties. In this work, confocal microscopy was used to show that our cryopreservation protocol for AM yielded viable cells in both the stromal and epithelial layers with favorable post-transplant outcome. AM was obtained from Caesarean-section placenta, processed into allograft pieces of different sizes (3 cm × 3 cm, 5 cm × 5 cm, and 10 cm × 10 cm) and cryopreserved in 10 % dimethyl sulfoxide using non-linear controlled rate freezing. Post-thaw cell viability in the entire piece of AM and in the stromal and epithelial cell layers was assessed using a dual fluorescent nuclear dye and compared to hypothermically stored AM, while surveys from surgical end-users provided information on post-transplant patient outcomes. There was no significant statistical difference in the cell viability in the entire piece, epithelial and stromal layers regardless of the size of allograft piece (p = 0.092, 0.188 and 0.581, respectively), and in the entire piece and stromal layer of hypothermically stored versus cryopreserved AM (p = 0.054 and 0.646, respectively). Surgical end-user feedback (n = 49) indicated that 16.3 % of AM allografts were excellent and 61.2 % were satisfactory. These results support the expanded clinical use of different sizes of cryopreserved AM allografts and address the issue of orientation of the AM during transplant for the treatment of dermatological defects and ocular surface disorders.


Assuntos
Aloenxertos/transplante , Âmnio/transplante , Criopreservação/métodos , Sobrevivência de Tecidos , Sobrevivência Celular , Células Epiteliais/citologia , Feminino , Humanos , Imageamento Tridimensional , Microscopia Confocal , Placenta/fisiologia , Gravidez , Coloração e Rotulagem , Células Estromais/citologia
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