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Substantial leaps in the understanding of quantum systems have been driven by exploring geometry, topology, dimensionality and interactions in ultracold atomic ensembles1-6. A system where atoms evolve while confined on an ellipsoidal surface represents a heretofore unexplored geometry and topology. Realizing an ultracold bubble-potentially Bose-Einstein condensed-relates to areas of interest including quantized-vortex flow constrained to a closed surface topology, collective modes and self-interference via bubble expansion7-17. Large ultracold bubbles, created by inflating smaller condensates, directly tie into Hubble-analogue expansion physics18-20. Here we report observations from the NASA Cold Atom Lab21 facility onboard the International Space Station of bubbles of ultracold atoms created using a radiofrequency-dressing protocol. We observe bubble configurations of varying size and initial temperature, and explore bubble thermodynamics, demonstrating substantial cooling associated with inflation. We achieve partial coverings of bubble traps greater than one millimetre in size with ultracold films of inferred few-micrometre thickness, and we observe the dynamics of shell structures projected into free-evolving harmonic confinement. The observations are among the first measurements made with ultracold atoms in space, using perpetual freefall to explore quantum systems that are prohibitively difficult to create on Earth. This work heralds future studies (in orbital microgravity) of the Bose-Einstein condensed bubble, the character of its excitations and the role of topology in its evolution.
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BACKGROUND: Six multidisciplinary cancer centers were selected and funded by the Merck Foundation (2017-2021) to collaborate in the Alliance to Advance Patient-Centered Cancer Care ("Alliance"), an initiative to improve patient access, minimize health disparities, and enhance the quality of patient-centered cancer care. These sites share their insights on implementation and expansion of their patient navigation efforts. METHODS: Patient navigation represents an evidence-based health care intervention designed to enhance patient-centered care and care coordination. Investigators at 6 National Cancer Institute-designated cancer centers outline their approaches to reducing health care disparities and synthesize their efforts to ensure sustainability and successful transferability in the management of patients with cancer and their families in real-world health care settings. RESULTS: Insights are outlined within the context of patient navigation program effectiveness and supported by examples from Alliance cancer center sites: 1) understand the patient populations, particularly underserved and high-risk patients; 2) capitalize on the existing infrastructure and institutional commitment to support and sustain patient navigation; and 3) build capacity by mobilizing community support outside of the cancer center. CONCLUSIONS: This process-level article reflects the importance of collaboration and the usefulness of partnering with other cancer centers to share interdisciplinary insights while undergoing intervention development, implementation, and expansion. These collective insights may be useful to staff at other cancer centers that look to implement, enhance, or evaluate the effectiveness of their patient navigation interventions.
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Neoplasias , Navegação de Pacientes , Disparidades em Assistência à Saúde , Humanos , National Cancer Institute (U.S.) , Neoplasias/terapia , Assistência Centrada no Paciente , Estados UnidosRESUMO
BACKGROUND: There are significant challenges in ensuring sufficient clinician participation in quality improvement training. Clinician capability has been identified as a barrier to the delivery of evidence-based care. Clinician training is an effective strategy to address this barrier, however, there are significant challenges in ensuring adequate clinician participation in training. This study aimed to assess the extent of participation by antenatal clinicians in evidence-based training to address alcohol consumption during pregnancy, and to assess differences in participation by profession. METHODS: A 7-month training initiative based on six evidence-based principles was implemented in a maternity service in New South Wales, Australia. Descriptive statistics described participation in training (% attending: any training; six evidence-based principles of training; all principles). Regression analyses examined differences by profession. RESULTS: Almost all antenatal clinicians participated in some training (182/186; 98%); 69% participated in ≥1 h of training (µ = 88.2mins, SD:56.56). The proportion of clinicians participating in training that satisfied each of the six principles ranged from 35% (training from peers and experts) to 82% (training was educational and instructional). Only 7% participated in training that satisfied all principles. A significantly higher proportion of midwifery compared to medical clinicians participated in training satisfying five of the six training principles. CONCLUSIONS: A training initiative based on evidence-based principles resulted in almost all clinicians receiving some training and 69% participating in at least 1 h of training. Variability between professions suggests training needs to be tailored to such groups. Further research is required to determine possible associations with care delivery outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).
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Tocologia , Melhoria de Qualidade , Consumo de Bebidas Alcoólicas , Austrália , Feminino , Humanos , New South Wales , GravidezRESUMO
PURPOSE: Online patient educational materials have historically been written at a higher-than-recommended sixth grade reading level. The objectives of this study were to assess the readability of online hand surgery patient educational materials from the official online patient resource website of the American Society for Surgery of the Hand (ASSH) and to compare changes in the readability of the current ASSH online patient educational materials with those in 2008 and 2015. METHODS: An internet-based study of all 88 English language patient educational materials on HandCare.org, the official online patient resource website of the ASSH, was performed. The readability of each article was assessed using the Flesch reading ease formula, Flesch-Kincaid grade level, Coleman-Liau index, Gunning-Fog index, and Simple Measure of Gobbledygook grade level. To evaluate the trend in the readability of ASSH online hand surgery patient educational materials, the Flesch-Kincaid grade levels of articles published in 2020 were compared with those of data published in 2008 and 2015. RESULTS: The average Flesch reading ease score of the patient educational materials was 57.6, which is at the high-school reading level. The average reading grade level of patient educational materials ranged from 9.0 to 12.3 depending on the readability metric used. The average Flesch-Kincaid grade level of all the ASSH patient educational materials was 9.8 in 2020, which is significantly better than 10.4 in 2008 but significantly worse than 8.5 in 2015. CONCLUSIONS: Online hand surgery patient educational materials continue to be written for the general public at a higher-than-recommended reading grade level. There has been no substantial improvement in the readability of online hand surgery patient educational materials since 2008. CLINICAL RELEVANCE: Improvements are needed in the readability of online patient educational materials to ensure that patients with all health literacy levels are able to comprehend and benefit from health information.
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Letramento em Saúde , Especialidades Cirúrgicas , Compreensão , Mãos/cirurgia , Humanos , Internet , Estados UnidosRESUMO
A computerized tomography (CT) scan is the current advanced imaging standard of care for evaluation and preoperative planning for tibial plateau fractures, but magnetic resonance imaging (MRI) is emerging as a better method to identify soft tissue injuries. This study compares MRI and CT for fracture classification, associated soft tissue injuries, and preoperative planning for tibial plateau fractures. MRI offers lack of radiation and enhanced soft tissue evaluation, and as a result improved preoperative planning. MRI was favored among survey respondents for preoperative planning, Schatzker classification, and surgical approach planning.
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Ortopedia , Lesões dos Tecidos Moles , Fraturas da Tíbia , Humanos , Imageamento por Ressonância Magnética , Inquéritos e Questionários , Tomografia Computadorizada por Raios XRESUMO
AIMS: Clusterin is a topologically dynamic chaperone protein with the ability to participate in both intra- and extacellular proteostasis. Clusterin has been shown to be upregulated in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) and has been shown to protect against TDP-43 protein misfolding in animal and cell models. Previous studies have demonstrated an association between the pathological burden of TDP-43 misfolding and cognitive deficits in ALS, demonstrating high specificity, but correspondingly low sensitivity owing to a subset of individuals with no evidence of cognitive deficits despite a high burden of TDP-43 pathology, called mismatch cases. METHODS: Hypothesizing that differences in the ability to cope with protein misfolding in these cases may be due to differences in expression of protective mechanisms such as clusterin expression, we assessed the spatial expression of clusterin and another chaperone protein, HspB8, in post mortem brain tissue of mismatch cases. We employed a modified in situ hybridization technique called BaseScope, with single cell, single transcript resolution. RESULTS: Mismatch cases demonstrated differential spatial expression of clusterin, with a predominantly neuronal pattern, compared to cases with cognitive manifestations of their TDP-43 pathology who demonstrated a predominantly glial distribution of expression. CONCLUSIONS: Our data suggest that, in individuals with TDP-43 pathology, predominantly neuronal expression of clusterin in extra-motor brain regions may indicate a cell protective mechanism delaying clinical manifestations such as cognitive dysfunction.
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Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/metabolismo , Clusterina/biossíntese , Disfunção Cognitiva/metabolismo , Neurônios/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/patologiaRESUMO
Therapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic-RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5-FI-RGD-rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5-FI-RGD-rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5-FI-RGD-rapamycin significantly inhibits fibroblast-mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin-conjugated multifunctional nanoparticles for PCa therapy.
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Dendrímeros/química , Integrina alfaVbeta3/metabolismo , Metástase Neoplásica/tratamento farmacológico , Peptídeos Cíclicos/química , Neoplasias da Próstata/tratamento farmacológico , Sirolimo/química , Sirolimo/uso terapêutico , Animais , Western Blotting , Linhagem Celular Tumoral , Células Cultivadas , Fibroblastos , Citometria de Fluxo , Humanos , Masculino , Camundongos , Células PC-3RESUMO
Background: We propose that arts based methodologies can be of value in the production and exchange of evidence in supporting public health related policy. This article reports on a collaborative piece of work resulting from two projects which took place in a former coal mining town in South Wales. Methods: We used a participatory framework whereby researchers, community members and artists co-produced 'evidence' through the creative arts to inform public policy. We collected a range of data using a number of different techniques, including interviews, focus groups and observation, but also included an extensive range of creative activities. Results: The data provided a diverse range of perspectives on how people of different ages live their lives. The People's Platform was a performance-based debate which was the culmination of the collaboration. The show involved a series of short performances with time for facilitated discussion in-between. It was felt that the show facilitated knowledge exchange on health and wellbeing issues that are usually difficult to express and understand through traditional forms of evidence. Conclusion: Whilst arts-based approaches are not free from risk, they offer an alternative form of knowledge as a necessary complement to the range of data available to policy makers.
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Arte , Prática Clínica Baseada em Evidências , Prática de Saúde Pública , Adulto , Prática Clínica Baseada em Evidências/métodos , Humanos , Entrevistas como Assunto , Formulação de Políticas , Política Pública , Características de Residência , País de GalesRESUMO
BACKGROUND: Patient-reported outcomes (PROs) (eg, symptoms, functioning) can inform patient management. However, patients and clinicians often have difficulty interpreting score meaning. The authors tested approaches for presenting PRO data to improve interpretability. METHODS: This mixed-methods study included an Internet survey of cancer patients/survivors, oncology clinicians, and PRO researchers circulated via snowball sampling, plus individual in-person interviews. Clinical importance was conveyed using 3 approaches (presented in random order): normal score range shaded green, concerning scores circled in red, and red threshold lines indicating normal versus concerning scores. Versions also tested 2 approaches to score directionality: higher = more (better for function, worse for symptoms) and higher = better for both function and symptoms. Qualitative data from online comments and in-person interviews supplemented quantitative results on interpretation accuracy, clarity, and the "most useful" format. RESULTS: The survey included 1113 respondents: 627 survivors, 236 clinicians, and 250 researchers, plus 10 patients and 10 clinicians who were purposively sampled interviewees. Interpretation accuracy ranged from 53% to 100%. The formats in which higher = better were interpreted more accurately versus those in which higher = more (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.07-1.58) and were more likely to be rated "very"/"somewhat" clear (OR, 1.39; 95% CI, 1.13-1.70) and "very" clear (OR, 1.36; 95% CI, 1.18-1.58). Red circle formats were interpreted more accurately than green-shaded formats when the first format presented (OR, 1.29; 95% CI, 1.00-1.65). Threshold-line formats were more likely to be rated "very" clear than green-shaded (OR, 1.43; 95% CI, 1.19-1.71) and red-circled (OR, 1.22, 95% CI, 1.02-1.46) formats. Threshold lines were most often selected as "most useful." CONCLUSIONS: The current results support presenting PRO data with higher = better directionality and threshold lines indicating normal versus concerning scores. Cancer 2017;123:1848-1859. © 2017 The Authors. Cancer published byWiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations aremade.
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Neoplasias , Oncologistas , Medidas de Resultados Relatados pelo Paciente , Pesquisadores , Sobreviventes , Atividades Cotidianas , Adulto , Idoso , Fadiga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Inquéritos e QuestionáriosRESUMO
BACKGROUND: An important limitation of many critical care trial designs is that they hypothesize large, and potentially implausible, reductions in mortality. Interpretation of trial results could be improved by systematic assessment of the plausibility of trial hypotheses; however, such assessment has not been attempted in the field of critical care medicine. The purpose of this study was to determine clinicians' views about prior probabilities and plausible effect sizes for ongoing critical care trials where the primary endpoint is landmark mortality. METHODS: We conducted a systematic review of clinical trial registries in September 2015 to identify ongoing critical care medicine trials where landmark mortality was the primary outcome, followed by a clinician survey to obtain opinions about ten large trials. Clinicians were asked to estimate the probability that each trial would demonstrate a mortality effect equal to or larger than that used in its sample size calculations. RESULTS: Estimates provided by individual clinicians varied from 0% to 100% for most trials, with a median estimate of 15% (IQR 10-20%). The median largest absolute mortality reduction considered plausible was 4.5% (IQR 3.5-5%), compared with a median absolute mortality reduction used in sample size calculations of 5% (IQR 3.6-10%) (P = 0.27). CONCLUSIONS: For some of the largest ongoing critical care trials, many clinicians regard prior probabilities as low and consider that plausible effects on absolute mortality are less than 5%. Further work is needed to determine whether pooled estimates obtained by surveying clinicians are replicable and accurate or whether other methods of estimating prior probability are preferred.
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Mortalidade Hospitalar , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa/normas , Resultados de Cuidados Críticos , Humanos , Sistema de Registros/estatística & dados numéricos , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
Ranaviruses have been isolated from many ectothermic vertebrates, and serological surveys of both amphibians and reptiles have shown the presence of ranaviral antibodies in a proportion of these populations. An enzyme-linked immunosorbent assay (ELISA) was developed to measure serum antibodies against ranavirus in Australian reptiles. The ELISA was validated with serum from challenge trials with Bohle iridovirus (BIV) in 6 reptilian species. A preliminary sero-survey of northern Queensland riparian reptile fauna (saw-shelled turtles Myuchelys latisternum, Krefft's river turtles Emydura macquarii krefftii, freshwater crocodiles Crocodylus johnstoni, as well as the snakes Boiga irregularis, Dendrelaphis punctulatus, Tropidonophis mairii, Morelia spilota, Liasis childreni and L. fuscus) revealed evidence of past exposure to Bohle iridoviral antigens in part of the population at several locations sampled. Furthermore, in Krefft's river turtles and freshwater crocodiles, a statistically significant trend was apparent for larger reptiles to be more likely to have BIV-reactive sera than smaller individuals. The use of adult tortoise populations as sentinels can assist in monitoring the presence of BIV in northern Australian freshwater streams, and thereby the potential dangers to native fauna from this agent.
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Jacarés e Crocodilos/sangue , Anticorpos Antivirais/sangue , Ranavirus/imunologia , Tartarugas/sangue , Animais , Austrália , Ensaio de Imunoadsorção Enzimática/veterinária , Testes SorológicosRESUMO
BACKGROUND: Researchers are required to seek consent from Indigenous communities prior to conducting research but there is inadequate information about how Indigenous people understand and become fully engaged with this consent process. Few studies evaluate the preference or understanding of the consent process for research with Indigenous populations. Lack of informed consent can impact on research findings. METHODS: The Picture Talk Project was initiated with senior Aboriginal leaders of the Fitzroy Valley community situated in the far north of Western Australia. Aboriginal people were interviewed about their understanding and experiences of research and consent processes. Transcripts were analysed using NVivo10 software with an integrated method of inductive and deductive coding and based in grounded theory. Local Aboriginal interpreters validated coding. Major themes were defined and supporting quotes sourced. RESULTS: Interviews with Aboriginal leaders (n = 20) were facilitated by a local Aboriginal Community Navigator who could interpret if necessary and provide cultural guidance. Participants were from all four major local language groups of the Fitzroy Valley; aged 31 years and above; and half were male. Themes emerging from these discussions included Research-finding knowledge; Being respectful of Aboriginal people, Working on country, and Being flexible with time; Working together with good communication; Reciprocity-two-way learning; and Reaching consent. CONCLUSION: The project revealed how much more there is to be learned about how research with remote Aboriginal communities should be conducted such that it is both culturally respectful and, importantly, meaningful for participants. We identify important elements in community consultation about research and seeking consent.
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Comunicação , Liderança , Havaiano Nativo ou Outro Ilhéu do Pacífico , Pesquisa , População Rural , Adulto , Austrália , Feminino , Humanos , Consentimento Livre e Esclarecido , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is a common operative treatment of compressive pathology of the cervical spinal cord, when caused by one or more degenerated intervertebral discs or related osteophytes. In addition to intra-operative radiographs to confirm spinal level before discectomy and implant position after insertion, traditional practice is to obtain post-operative antero-posterior and lateral plain radiographs (XR) before hospital discharge, despite a paucity of evidence supporting their benefit to patient care. Minimising unnecessary radiation to radiosensitive neck structures is desirable, and furthermore, with increasing financial pressure on healthcare resources, routine investigations should be clinically justified and evidence-based. We aim to compare the utility of routine post-operative cervical spine X-rays following ACDF. METHODS: We compare two groups of consecutive patients undergoing ACDF in a single UK neurosurgical centre. The first group (n = 109) received routine post-operative XR imaging, and the second group (n = 113) received radiographs only when clinically indicated. RESULTS: There were no differences in post-operative complication rates (4.6% vs. 5.3%), or requirement for further imaging or of further operative intervention (1.8% vs. 0.9%). The group that did not have routine post-operative radiographs had a significantly shorter stay in hospital (median two days vs. three days). There were no patients in either group where post-operative XR changed clinical management and mandated revision surgery or further imaging. All cases requiring surgery or further imaging were identified by clinical deterioration. CONCLUSIONS: We suggest that the practice of obtaining routine radiographs of the cervical spine following ACDF should be abandoned, unless there is a clear clinical indication.
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Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/economia , Discotomia/métodos , Cuidados Pós-Operatórios/economia , Cuidados Pós-Operatórios/métodos , Análise Custo-Benefício , Discotomia/efeitos adversos , Feminino , Custos de Cuidados de Saúde , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neurocirurgia/economia , Neurocirurgia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Coluna Vertebral/diagnóstico por imagem , Resultado do Tratamento , Reino Unido , Raios XRESUMO
OBJECTIVES: Recent literature has drawn attention to the potential inadequacy of frequentist analysis and threshold p values as tools for reporting outcomes in clinical trials. The fragility index, which is a measure of how many events the statistical significance of a result depends on, has been suggested as a means to aid the interpretation of trial results. This study aimed to calculate the fragility index of clinical trials in critical care medicine reporting a statistically significant effect on mortality (increasing or decreasing mortality). DATA SOURCES: Literature search (PubMed/MEDLINE) to identify all multicenter randomized controlled trials in critical care medicine. STUDY SELECTION: We identified 862 trials; of which 56 fulfilled eligibility criteria and were included in our analysis. DATA EXTRACTION: Calculation of fragility index for trials reporting a statistically significant effect on mortality, and analysis of the relationship between trial characteristics and fragility index. DATA SYNTHESIS: The median fragility index was 2 (interquartile range, 1-3.5), and greater than 40% of trials had a fragility index of less than or equal to 1. 12.5% of trials reported loss to follow-up greater than their fragility index. Trial sample size was positively correlated, and reported p value was negatively correlated, with fragility index. CONCLUSIONS: In critical care trials reporting statistically significant effects on mortality, the findings often depend on a small number of events. Critical care clinicians should be wary of basing decisions on trials with a low fragility index. We advocate the reporting of fragility index for future trials in critical care to aid interpretation and decision making by clinicians.
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Cuidados Críticos/estatística & dados numéricos , Interpretação Estatística de Dados , Mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Estudos Multicêntricos como AssuntoRESUMO
We aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in New South Wales (NSW) using the Paediatric Active Enhanced Disease Surveillance (PAEDS) network to inform methodology for the nationwide Australian childhood encephalitis (ACE) study. We piloted active surveillance for suspected encephalitis from May to December 2013 at the Children's Hospital at Westmead, Sydney, NSW. Cases were ascertained using four screening methods: weekday nurse screening of admission records (PAEDS), cerebrospinal fluid (CSF) microscopy records, magnetic resonance imaging (MRI) reports, and pharmacy dispensing records. Comprehensive clinical data were prospectively collected on consented participants and subsequently reviewed by an expert panel. Cases were categorized as confirmed encephalitis or 'not encephalitis'; encephalitis cases were sub-categorized as infectious, immune-mediated or unknown. We performed an ICD-10 diagnostic code audit of hospitalizations for the pilot period. We compared case ascertainment in the four screening methods and with the ICD code audit. Forty-eight cases of suspected encephalitis were identified by one or more methods. PAEDS was the most efficient mechanism (yield 34%), followed by MRI, CSF, and pharmacy audits (yield 14%, 12%, and 7% respectively). Twenty-five cases met the criteria for confirmed encephalitis. PAEDS was the most sensitive of the mechanisms for confirmed encephalitis (92%) with a positive predictive value (PPV) of 72%. The ICD audit was moderately sensitive (64%) but poorly specific (Sp 9%, PPV 14%). Of the 25 confirmed encephalitis cases, 19 (76%) were sub-categorized as infectious, three (12%) were immune-mediated, and three (12%) were 'unknown'. We identified encephalitis cases associated with two infectious disease outbreaks (enterovirus 71, parechovirus 3). PAEDS is an efficient, sensitive and accurate surveillance mechanism for detecting cases of childhood encephalitis including those associated with emerging infectious diseases. Active surveillance significantly increases the ascertainment of encephalitis cases compared with passive approaches.
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Encefalite/epidemiologia , Vigilância da População/métodos , Adolescente , Criança , Pré-Escolar , Encefalite/virologia , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , New South Wales/epidemiologia , Projetos PilotoRESUMO
Gene regulation at functional elements (e.g., enhancers, promoters, insulators) is governed by an interplay of nucleosome remodeling, histone modifications, and transcription factor binding. To enhance our understanding of gene regulation, the ENCODE Consortium has generated a wealth of ChIP-seq data on DNA-binding proteins and histone modifications. We additionally generated nucleosome positioning data on two cell lines, K562 and GM12878, by MNase digestion and high-depth sequencing. Here we relate 14 chromatin signals (12 histone marks, DNase, and nucleosome positioning) to the binding sites of 119 DNA-binding proteins across a large number of cell lines. We developed a new method for unsupervised pattern discovery, the Clustered AGgregation Tool (CAGT), which accounts for the inherent heterogeneity in signal magnitude, shape, and implicit strand orientation of chromatin marks. We applied CAGT on a total of 5084 data set pairs to obtain an exhaustive catalog of high-resolution patterns of histone modifications and nucleosome positioning signals around bound transcription factors. Our analyses reveal extensive heterogeneity in how histone modifications are deposited, and how nucleosomes are positioned around binding sites. With the exception of the CTCF/cohesin complex, asymmetry of nucleosome positioning is predominant. Asymmetry of histone modifications is also widespread, for all types of chromatin marks examined, including promoter, enhancer, elongation, and repressive marks. The fine-resolution signal shapes discovered by CAGT unveiled novel correlation patterns between chromatin marks, nucleosome positioning, and sequence content. Meta-analyses of the signal profiles revealed a common vocabulary of chromatin signals shared across multiple cell lines and binding proteins.
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Montagem e Desmontagem da Cromatina , Heterogeneidade Genética , Sequências Reguladoras de Ácido Nucleico , Sítios de Ligação/genética , Linhagem Celular , Análise por Conglomerados , Biologia Computacional/métodos , Humanos , Células K562 , Nucleossomos/genética , Nucleossomos/metabolismo , Ligação Proteica , Software , Sítio de Iniciação de TranscriçãoRESUMO
We measure the shear viscosity for a resonantly interacting Fermi gas as a function of temperature from nearly the ground state through the superfluid phase transition into the high temperature regime. Further, we demonstrate an iterative method to estimate the local shear viscosity coefficient α(S)(θ) versus reduced temperature θ from the cloud-averaged measurements ⟨α(S)⟩, and compare α(S) to several microscopic theories. We find that α(S) reveals features that were previously hidden in ⟨α(S)⟩.
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OBJECTIVES: The objectives of this paper are to prospectively determine the incidence of paediatric systemic lupus erythematosus (pSLE) in Australia as well as describe the demographics, clinical presentation and one-year outcome. STUDY DESIGN: Newly diagnosed cases of pSLE were ascertained prospectively from October 2009 to October 2011 through the Australian Paediatric Surveillance Unit (a national monthly surveillance scheme for notification of childhood rare diseases) as well as national subspecialty groups. Questionnaires were sent to notifying physicians at presentation and at one year. RESULTS: The annual incidence rate was 0.32 per 10(5) children aged less than 16 years. The incidence was significantly higher in children of Asian or Australian Aboriginal and Torres Strait Islander parents. Approximately one-third of children underwent a renal biopsy at presentation and 7% required dialysis initially although only one child had end-stage kidney disease (ESKD) at one-year follow-up. CONCLUSION: The incidence of pSLE in Australia is comparable to that worldwide with a significantly higher incidence seen in children of Asian and Australian Aboriginal and Torres Strait Islander backgrounds. Renal involvement is common but progression to ESKD, at least in the short term, is rare.
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Povo Asiático/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/epidemiologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Adolescente , Idade de Início , Anticorpos Antinucleares/sangue , Austrália/epidemiologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/patologia , Nefrite Lúpica/terapia , Masculino , Estudos Prospectivos , Proteinúria/etiologia , Febre Reumática/etiologiaRESUMO
We measure the static shear viscosity η in a two-component Fermi gas near a broad collisional (Feshbach) resonance, as a function of interaction strength and energy. We find that η has both a quadratic and a linear dependence on the interaction strength 1/(k(FI)a), where a is the s-wave scattering length and k(FI) is the Fermi wave vector for an ideal gas at the trap center. For energies above the superfluid transition, the minimum in η as a function of interaction strength is significantly shifted toward the BEC side of resonance, to 1/(k(FI)a)≃0.25.
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We precisely test scale invariance and examine local thermal equilibrium in the hydrodynamic expansion of a Fermi gas of atoms as a function of interaction strength. After release from an anisotropic optical trap, we observe that a resonantly interacting gas obeys scale-invariant hydrodynamics, where the mean square cloud size