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For the first time, the (d,^{2}He) reaction was successfully used in inverse kinematics to extract the Gamow-Teller transition strength in the ß^{+} direction from an unstable nucleus. The new technique was made possible by the use of an active-target time-projection chamber and a magnetic spectrometer, and opens a path to addressing a range of scientific challenges, including in astrophysics and neutrino physics. In this Letter, the nucleus studied was ^{14}O, and the Gamow-Teller transition strength to ^{14}N was extracted up to an excitation energy of 22 MeV. The data were compared to shell-model and state-of-the-art coupled-cluster calculations. Shell-model calculations reproduce the measured Gamow-Teller strength distribution up to about 15 MeV reasonably well, after the application of a phenomenological quenching factor. In a significant step forward to better understand this quenching, the coupled-cluster calculation reproduces the full strength distribution well without such quenching, owing to the large model space, the inclusion of strong correlations, and the coupling of the weak interaction to two nucleons through two-body currents.
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Núcleo Celular , Física , Fenômenos BiomecânicosRESUMO
BACKGROUND: Vigorous Intermittent Lifestyle Physical Activity (VILPA) refers to brief bouts of vigorous intensity physical activity performed as part of daily living. VILPA has been proposed as a novel concept to expand physical activity options among the least active. As a nascent area of research, factors which impede or encourage VILPA in physically inactive adults are yet to be explored. Such information is pertinent in the design of future interventions. We examined the barriers and enablers of VILPA among physically inactive adults using the Capability, Opportunity, Motivation, Behavior (COM-B) model as a conceptual framework. METHODS: We recruited a sample of self-identified physically inactive middle-aged and older adults (N = 78) based in Australia to take part in 19 online focus groups across three age groups: young-middle (age 35-44), middle (age 45-59) and old (age 60-76). We analyzed interviews using a critical realist approach to thematic analysis. Identified barriers and enablers were subsequently mapped onto the COM-B model components. RESULTS: The data generated 6 barriers and 10 enablers of VILPA that corresponded to COM-B concepts. Barriers included physical limitations (physical capability), perceptions of aging, need for knowledge (psychological capability), environmental constraints (physical opportunity), perceptions of effort and energy, and fear (automatic motivation). Enablers included convenience, reframing physical activity as purposeful movement, use of prompts and reminders (physical opportunity), normalization of taking the active option, gamification (social opportunity), sense of achievement, health improvements, personally salient rewards (reflective motivation), identity fit, and changing from effortful deliberation to habitual action (automatic motivation). CONCLUSION: The barriers and enablers of VILPA span capability, opportunity, and motivation beliefs. Promoting the time-efficient nature and simplicity of VILPA requiring no equipment or special gym sessions, the use of prompts and reminders at opportune times, and habit formation strategies could capitalize on the enablers. Addressing the suitability of the small bouts, the development of specific guidelines, addressing safety concerns, and explicating the potential benefits of, and opportunities to do, VILPA could ameliorate some of the barriers identified. Future VILPA interventions may require limited age customization, speaking to the potential for such interventions to be delivered at scale.
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Exercício Físico , Motivação , Pessoa de Meia-Idade , Humanos , Idoso , Adulto , Grupos Focais , Exercício Físico/psicologia , Comportamento Sedentário , Austrália , Pesquisa QualitativaRESUMO
OBJECTIVE: To investigate the alignment of national health priorities with a country's burden of disease as measured by disability-adjusted life years (DALYs). METHODS: We identified priorities in national health plans and the 20 most burdensome conditions measured by DALYs from the 2017 Global Burden of Disease Study. We computed point-biserial correlations (rpb) between DALYs and being nominated as a health priority and the pooled proportion (95% confidence intervals [CIs]) of the 20 most burdensome conditions nominated as a priority across countries. RESULTS: We identified national health plans and official governmental websites in 145 countries. There was little to no correlation (rpb = 0.06, 95% CI: 0.02 to 0.09) between national DALY data and whether a condition was nominated as a health priority. The pooled proportion of the 20 most burdensome conditions nominated as priorities across countries was 46%. HIV/AIDS had the greatest number of nominations as a national health priority (62 countries) as well as the greatest match with the burden of disease (among the top 20 most burdensome conditions in 51 [82%] countries). Low back pain, headache disorders and congenital birth defects had the lowest proportion of nominations as health priorities in countries where they were in the top 20 most burdensome conditions (6%, 6% and 11%, respectively). CONCLUSION: Globally, there were low correlations between national health priorities and GBD estimates on disease burden. Failing to prioritise health priorities according to burden may mean that insufficient resources have been directed to improve health outcomes for people with those health conditions.
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Pessoas com Deficiência , Expectativa de Vida , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Prioridades em Saúde , Saúde Global , Efeitos Psicossociais da Doença , Fatores de RiscoRESUMO
BACKGROUND: 'Stable disease (SD)' as per RECIST is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs). This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. Understanding SD would facilitate drug development and improve precision in correlative research. PATIENTS AND METHODS: A systematic review was carried out to characterize SD in ICI trials. SD and objective response were compared to proliferation index using The Cancer Genome Atlas gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of non-small-cell lung cancer (NSCLC). Serial cutpoints of two variables, % best overall response and progression-free survival (PFS), were tested to define a subgroup of patients with SD with similar survival as responders. Results were then tested in external validation cohorts. RESULTS: Among trials of ICIs (59 studies, 14 280 patients), SD ranged from 16% to 42% in different tumor types and was associated with disease-specific proliferation index (ρ = -0.75, P = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of NSCLC [1220 patients, 313 (26%) with SD to ICIs], PFS ranged widely in SD (0.2-49 months, median 4.9 months). The subset with PFS >6 months and no tumor growth mirrored partial response (PR) minor (overall survival hazard ratio 1.0) and was proposed as the definition of SD responder. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab and found to apply in tumor types treated with immunotherapy in which depth and duration of benefit were correlated. CONCLUSIONS: RECIST-defined SD to immunotherapy is common, heterogeneous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS >6 months and no tumor growth may be considered 'SD responders'. This definition may improve the efficiency of and insight derivable from clinical and translational research.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologiaRESUMO
The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.
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Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.
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Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Manejo da Dor/estatística & dados numéricos , Analgésicos/uso terapêutico , Tratamento Farmacológico/estatística & dados numéricos , Humanos , Estudos Observacionais como AssuntoRESUMO
We describe a unique case of hyperphosphatemia associated with a very high bone turnover rate in a 51-year-old postmenopausal woman with undiagnosed anorexia nervosa (AN) who presented with a low-trauma hip fracture. In view of her severely malnourished state, she was not fit for surgery. She was treated according to a refeeding protocol that mandated bed rest. Contrary to expectation, she developed sustained hyperphosphatemia and borderline hypercalcemia. Bone remodelling markers, both resorption and formation, were markedly elevated. Parathyroid hormone (PTH) was low-normal at 1.7 pmol/L, C-terminal fibroblast growth factor 23 (FGF23) was high at 293 RU/ml, but tubular maximum reabsorption of phosphate (TmPO4/GFR) was elevated at 1.93 mmol/L. Denosumab 60 mg was administered that was followed by: rapid normalisation of serum phosphate; normalisation of resorption markers, transient hypocalcaemia with secondary hyperparathyroidism, and normalisation of both TmPO4/GFR and C-terminal FGF23. We speculate that prolonged immobilization as part of AN management led to a high remodelling state followed by hyperphosphatemia and high-normal calcium with appropriate suppression of PTH and that marked hyperphosphatemia and high TmP/GFR despite high FGF23 indicates the necessity of PTH adequacy for excess FGF23 to lower TmP/GFR.
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Anorexia Nervosa , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Hiperfosfatemia , Anorexia Nervosa/complicações , Remodelação Óssea , Cálcio , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Humanos , Hiperfosfatemia/etiologia , Pessoa de Meia-Idade , Hormônio Paratireóideo , FosfatosRESUMO
Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.
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Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Prolapso de Órgão Pélvico/cirurgia , Fatores Etários , Tomada de Decisões , Feminino , Humanos , IncidênciaRESUMO
Purpose (1) to examine the ability of the Örebro Musculoskeletal Pain Screening Questionnaire-short version (ÖMPSQ-SF) to predict time to return to pre-injury work duties (PID) following a work-related soft tissue injury (regardless of body location); and (2) to examine the appropriateness of 50/100 as a suitable cut-off score for case identification. Methods Injured workers (IW) from six public hospitals in Sydney, Australia, who had taken medically-sanctioned time off work due to their injury, were recruited by insurance case managers within 5-15 days of their injury. Eligible participants (N = 213 in total) were administered the ÖMPSQ-SF over the telephone by the case manager. For objective (1) Cox proportional hazards regression analysis was used to predict days to return to PID using the ÖMPSQ-SF. For objective (2) receiver operator characteristic (ROC) analysis was used to determine the ÖMPSQ-SF total score that optimises sensitivity and specificity in detecting whether or not participants had returned to PID within 2-7 weeks. Results The total ÖMPSQ-SF score significantly predicted number of days to return to PID, such that for every 1-point increase in the total ÖMPSQ-SF score the predicted chance of returning to work reduced by 4% (i.e., hazard ratio = 0.96), p < 0.001. Sensitivity and specificity for the ROC analysis comparing ÖMPSQ-SF total score to return to PID within 2-7 weeks suggested 48 as the optimal cut off (sensitivity = 0.65, specificity = 0.79). Conclusion The results provide strong support for the use of the ÖMPSQ-SF in an applied setting for identifying those IW likely to have delayed RTW when administered within 15 days of the injury. While a score of 48/100 was the optimal cut point for sensitivity and specificity, pragmatically, 50/100 should be acceptable as a cut-off in future studies of this type.
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Avaliação da Deficiência , Traumatismos Ocupacionais/epidemiologia , Retorno ao Trabalho/estatística & dados numéricos , Inquéritos e Questionários/normas , Estudos de Casos e Controles , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Traumatismos Ocupacionais/reabilitação , Indenização aos Trabalhadores/estatística & dados numéricosRESUMO
The purpose of this study was to describe sources of variability in obesity-related variables in 6022 children aged 9-11 years from 12 countries. The study design involved recruitment of students, nested within schools, which were nested within study sites. Height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated; sleep duration and total and in-school moderate-to-vigorous physical activity (MVPA) and sedentary time were measured by accelerometry; and diet scores were obtained by questionnaire. Variance in most variables was largely explained at the student level: BMI (91.9%), WC (93.5%), sleep (75.3%), MVPA (72.5%), sedentary time (76.9%), healthy diet score (88.3%), unhealthy diet score (66.2%), with the exception of in-school MVPA (53.8%) and in-school sedentary time (25.1%). Variance explained at the school level ranged from 3.3% for BMI to 29.8% for in-school MVPA, and variance explained at the site level ranged from 3.2% for WC to 54.2% for in-school sedentary time. In general, more variance was explained at the school and site levels for behaviors than for anthropometric traits. Given the variance in obesity-related behaviors in primary school children explained at school and site levels, interventions that target policy and environmental changes may enhance obesity intervention efforts.
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Tamanho Corporal/fisiologia , Exercício Físico/fisiologia , Obesidade Infantil/epidemiologia , Índice de Massa Corporal , Criança , Comportamento Infantil , Estudos Transversais , Humanos , Obesidade Infantil/fisiopatologia , Comportamento SedentárioRESUMO
BACKGROUND: The PACE Plus trial was a multi-center, double-blinded, superiority randomized controlled trial (RCT) conducted in patients from Dutch general practice to investigate the efficacy of paracetamol and NSAIDs in acute non-specific low back pain (LBP). Because insufficient numbers of patients could be recruited (only four out of the required 800 patients could be recruited over a period of 6 months), the trial was prematurely terminated in February 2017, 6 months after the start of recruitment. This article aims to transparently communicate the discontinuation of PACE Plus and to make recommendations for future studies. METHODS: General Practitioners (GPs) from 36 participating practices received a one-question survey in which they were asked to give the three most important factors that in their opinion contributed to failure of patient recruitment. RESULTS: GPs of 33 out of 36 (92%) participating practices sent a response. A total of 81 factors were reported. These have been categorized into patient factors (26 out of 81 comments, 32%), GP factors (39 out of 81 comments, 48%) and research factors (16 out of 81 comments, 20%). DISCUSSION: Patient recruitment in the PACE Plus trial may have failed due to inefficient medication distribution, recruitment of incident rather than prevalent cases, a design that was too complicated, adequate self-management of LBP, patient expectations different from the trial's scope and lack of time of participating GPs. Substantial differences in design may explain why the preceding PACE trial did manage to successfully complete patient recruitment. CONCLUSION: Although the PACE Plus trial was terminated as a result of insufficient patient inclusion, the research questions addressed in this trial remain relevant but unanswered. We hope that lessons learned from the discontinuation of PACE Plus and corresponding recommendations may be helpful in the design of upcoming research projects in LBP in general practice. TRIAL REGISTRATION: Dutch Trial Registration NTR6089, registered September 14th 2016.
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Medicina Geral/métodos , Medicina Geral/tendências , Estudos Multicêntricos como Assunto/métodos , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Inquéritos e Questionários , Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Clínicos Gerais/tendências , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/epidemiologia , Países Baixos/epidemiologiaRESUMO
BACKGROUND: The 3 "movement behaviours" of sleep, screen time, and physical activity are associated with a wide range of health outcomes in children. This study examined whether these behaviours cluster together within individuals in Australian primary school children. METHODS: Three datasets including 4,449 9- to 11-year-old children were interrogated-(a) Obesity Prevention and Lifestyle (OPAL), (b) the International Study of Children, Obesity, Lifestyle and Environment (ISCOLE), and (c) the National Children's Nutrition and Physical Activity Survey (NCNPAS). The surveys measured movement behaviours using different instruments (accelerometry, use of time recall, and questionnaires) and different operationalizations of compliance. Observed frequencies of compliance with various combinations of guidelines were compared with expected frequencies based on the assumption of independence, using chi-square tests. RESULTS: Compliance with the sleep guidelines was relatively high (72%, 75%, and 79% in the OPAL, ISCOLE, and NCNPAS datasets, respectively), and compliance with the screen (18%, 35%, and 22%) and physical activity (33%, 57%, and 87%) guidelines was generally lower. Against expectation, there was no evidence of clustering in any of the datasets (p > .99). CONCLUSIONS: Compliance with movement behaviour guidelines does not cluster within individuals in 9- to 11-year-old Australian children. It may be unlikely that fostering compliance with one guideline will have a flow-on effect to the others. Temporal trade-offs (i.e., the need to choose one movement behaviour above another) in the 24-hr day may contribute to the lack of clustering.
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Comportamento Infantil/psicologia , Exercício Físico , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Obesidade Infantil/prevenção & controle , Comportamento Sedentário , Austrália/epidemiologia , Criança , Comportamento Infantil/fisiologia , Fenômenos Fisiológicos da Nutrição Infantil , Análise por Conglomerados , Dieta , Feminino , Fidelidade a Diretrizes , Guias como Assunto , Humanos , Masculino , Obesidade Infantil/epidemiologia , Sono , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Reconstruction of clonal evolution is critical for understanding tumor progression and implementing personalized therapies. This is often done by clustering somatic variants based on their cellular prevalence estimated via bulk tumor sequencing of multiple samples. The clusters, consisting of the clonal marker variants, are then ordered based on their estimated cellular prevalence to reconstruct clonal evolution trees, a process referred to as 'clonal ordering'. However, cellular prevalence estimate is confounded by statistical variability and errors in sequencing/data analysis, and therefore inhibits accurate reconstruction of the clonal evolution. This problem is further complicated by intra- and inter-tumor heterogeneity. Furthermore, the field lacks a comprehensive visualization tool to facilitate the interpretation of complex clonal relationships. To address these challenges we developed ClonEvol, a unified software tool for clonal ordering, visualization, and interpretation. MATERIALS AND METHODS: ClonEvol uses a bootstrap resampling technique to estimate the cellular fraction of the clones and probabilistically models the clonal ordering constraints to account for statistical variability. The bootstrapping allows identification of the sample founding- and sub-clones, thus enabling interpretation of clonal seeding. ClonEvol automates the generation of multiple widely used visualizations for reconstructing and interpreting clonal evolution. RESULTS: ClonEvol outperformed three of the state of the art tools (LICHeE, Canopy and PhyloWGS) for clonal evolution inference, showing more robust error tolerance and producing more accurate trees in a simulation. Building upon multiple recent publications that utilized ClonEvol to study metastasis and drug resistance in solid cancers, here we show that ClonEvol rediscovered relapsed subclones in two published acute myeloid leukemia patients. Furthermore, we demonstrated that through noninvasive monitoring ClonEvol recapitulated the emerging subclones throughout metastatic progression observed in the tumors of a published breast cancer patient. CONCLUSIONS: ClonEvol has broad applicability for longitudinal monitoring of clonal populations in tumor biopsies, or noninvasively, to guide precision medicine. AVAILABILITY: ClonEvol is written in R and is available at https://github.com/ChrisMaherLab/ClonEvol.
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Evolução Clonal , Leucemia Mieloide Aguda/genética , Células Clonais , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucemia Mieloide Aguda/patologia , Medicina de PrecisãoRESUMO
BACKGROUND: Low back pain is common and associated with a considerable burden to patients and society. There is uncertainty regarding the relative benefit of paracetamol and diclofenac and regarding the additional effect of pain medication compared with advice only in patients with acute low back pain. This trial will assess the effectiveness of paracetamol, diclofenac and placebo for acute low back pain over a period of 4 weeks. Furthermore, this trial will assess the additional effectiveness of paracetamol, diclofenac and placebo compared with advice only for acute low back pain over a period of 4 weeks. METHODS: The PACE Plus trial is a multi-center, placebo-blinded, superiority randomized controlled trial in primary care, with a follow-up of 12 weeks. Patients with acute low back pain aged 18-60 years presenting in general practice will be included. Patients are randomized into four groups: 1) Advice only (usual care conforming with the clinical guideline of the Dutch College of General Practitioners); 2) Advice and paracetamol; 3) Advice and diclofenac; 4) Advice and placebo. The primary outcome is low back pain intensity measured with a numerical rating scale (0-10). Secondary outcomes include compliance to treatment, disability, perceived recovery, costs, adverse reactions, satisfaction, sleep quality, co-interventions and adequacy of blinding. Between group differences for low back pain intensity will be evaluated using a repeated measurements analysis with linear effects models. An economic evaluation will be performed using a cost-effectiveness analysis with low back pain intensity and a cost-utility analysis with quality of life. Explorative analyses will be performed to assess effect modification by predefined variables. Ethical approval has been granted. Trial results will be released to an appropriate peer-viewed journal. DISCUSSION: This paper presents the design of the PACE Plus trial: a multi-center, placebo-blinded, superiority randomized controlled trial in primary care that will assess the effectiveness of advice only, paracetamol, diclofenac and placebo for acute low back pain. TRIAL REGISTRATION: Dutch Trial Registration NTR6089 , registered September 14th, 2016. PROTOCOL: Version 4, June 2016.
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Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/uso terapêutico , Dor Lombar/tratamento farmacológico , Atenção Primária à Saúde , Aconselhamento Diretivo , Humanos , Projetos de PesquisaRESUMO
OBJECTIVES: To examine whether meeting vs not meeting movement/non-movement guidelines (moderate-to-vigorous physical activity [MVPA], screen time, sleep duration), and combinations of these recommendations, are associated with health-related quality of life (HRQoL) in children from 12 countries in five major geographic regions of the world and explore whether the associations vary by study site. STUDY DESIGN: Observational, multinational cross-sectional study. METHODS: This study included 6106 children aged 9-11 years from sites in Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Participants completed the KIDSCREEN-10 to provide a global measure of their HRQoL. Sleep duration and MVPA were assessed using 24-h accelerometry. Screen time was assessed through self-report. Meeting the recommendations was defined as ≥60 min/day for MVPA, ≤2 h/day for screen time, and between 9 and 11 h/night for sleep duration. Age, sex, highest parental education, unhealthy diet pattern score, and body mass index z-score were included as covariates in statistical models. RESULTS: In the full sample, children meeting the screen time recommendation, the screen time + sleep recommendation, and all three recommendations had significantly better HRQoL than children not meeting any of these guidelines. Differences in HRQoL scores between sites were also found within combinations of movement/non-movement behaviors. For example, while children in Australia, Canada, and USA self-reported better HRQoL when meeting all three recommendations, children in Kenya and Portugal reported significantly lower HRQoL when meeting all three recommendations (relative to not meeting any). CONCLUSIONS: Self-reported HRQoL is generally higher when children meet established movement/non-movement recommendations. However, differences between study sites also suggest that interventions aimed at improving lifestyle behaviors and HRQoL should be locally and culturally adapted.
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Exercício Físico , Fidelidade a Diretrizes/estatística & dados numéricos , Guias como Assunto , Nível de Saúde , Qualidade de Vida , Austrália , Brasil , Canadá , Criança , China , Colômbia , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Índia , Quênia , Masculino , Autorrelato , Estados UnidosRESUMO
BACKGROUND: Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare liver tumor defined by the presence of both pure FL-HCC and conventional HCC components, represents up to 25% of cases of FL-HCC, and has been associated with worse prognosis. Recent genomic characterization of pure FL-HCC identified a highly recurrent transcript fusion (DNAJB1:PRKACA) not found in conventional HCC. PATIENTS AND METHODS: We performed exome and transcriptome sequencing of a case of mFL-HCC. A novel BAC-capture approach was developed to identify a 400 kb deletion as the underlying genomic mechanism for a DNAJB1:PRKACA fusion in this case. A sensitive Nanostring Elements assay was used to screen for this transcript fusion in a second case of mFL-HCC, 112 additional HCC samples and 44 adjacent non-tumor liver samples. RESULTS: We report the first comprehensive genomic analysis of a case of mFL-HCC. No common HCC-associated mutations were identified. The very low mutation rate of this case, large number of mostly single-copy, long-range copy number variants, and high expression of ERBB2 were more consistent with previous reports of pure FL-HCC than conventional HCC. In particular, the DNAJB1:PRKACA fusion transcript specifically associated with pure FL-HCC was detected at very high expression levels. Subsequent analysis revealed the presence of this fusion in all primary and metastatic samples, including those with mixed or conventional HCC pathology. A second case of mFL-HCC confirmed our finding that the fusion was detectable in conventional components. An expanded screen identified a third case of fusion-positive HCC, which upon review, also had both conventional and fibrolamellar features. This screen confirmed the absence of the fusion in all conventional HCC and adjacent non-tumor liver samples. CONCLUSION: These results indicate that mFL-HCC is similar to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a diagnostic tool for both pure and mFL-HCC.
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Carcinoma Hepatocelular/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Proteínas de Choque Térmico HSP40/genética , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Exoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Mutação , Proteínas de Fusão Oncogênica/genética , Transcriptoma/genéticaRESUMO
BACKGROUND: It has been hypothesised that an 'activitystat' may biologically regulate energy expenditure or physical activity levels, thereby limiting the effectiveness of physical activity interventions. Using a randomised controlled trial design, the aim of this study was to investigate the effect of a six-week exercise stimulus on energy expenditure and physical activity, in order to empirically test this hypothesis. METHODS: Previously inactive adults (n = 129) [age (mean ± SD) 41 ± 11 year; body mass index 26.1 ± 5.2 kg/m(2)] were randomly allocated to a Control group (n = 43) or a 6-week Moderate (150 min/week) (n = 43) or Extensive (300 min/week) (n = 43) exercise intervention group. Energy expenditure and physical activity were measured using a combination of accelerometry (total counts, minutes spent in moderate to vigorous physical activity) and detailed time use recalls using the Multimedia Activity Recall for Children and Adults (total daily energy expenditure, minutes spent in moderate to vigorous physical activity) at baseline, mid- and end-intervention and 3- and 6-month follow up. Resting metabolic rate was measured at baseline and end-intervention using indirect calorimetry. Analysis was conducted using random effects mixed modeling. RESULTS: At end-intervention, there were statistically significant increases in all energy expenditure and physical activity variables according to both accelerometry and time use recalls (p < 0.001) in the Moderate and Extensive groups, relative to Controls. There was no significant change in resting metabolic rate (p = 0.78). CONCLUSION: Taken together, these results show no evidence of an "activitystat" effect. In the current study, imposed exercise stimuli of 150-300 min/week resulted in commensurate increases in overall energy expenditure and physical activity, with no sign of compensation in either of these constructs. TRIAL REGISTRATION NUMBER: ACTRN12610000248066 (registered prospectively 24 March 2010).
Assuntos
Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Promoção da Saúde/métodos , Acelerometria , Adulto , Retroalimentação , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
After a long hard struggle, the start of this decade saw the fight to eradicate polio from the Eastern Mediterranean Region appearing to bear fruit. In 2011 and 2012, only two countries in the Region were reporting wild poliovirus - Pakistan and Afghanistan, two of the last endemic countries in the world. By the end of 2012, when only 95 cases were reported in total from the Region, it seemed that finally stopping the transmission of poliovirus was just around the corner. The number of cases and countries were at the lowest-ever recorded levels.
RESUMO
PURPOSE: To investigate the association between symptom severity and physical activity participation in people with acute non-specific low back pain (LBP). METHODS: The sample included a total of 999 patients who presented to primary care with an acute episode of low back pain. Symptom severity, in terms of activity limitation and severity of pain; and physical activity participation before (habitual) and after pain onset were assessed using self-report questionnaires. All participants were interviewed within 14 days of pain onset. RESULTS: At interview most of the participants (87.5 %) reported having moderate to extreme activity limitation due to back pain. There was a significant decrease in physical activity participation after pain onset (mean difference: -176 min, 95 % CI 327-400; p < 0.0001) but no association between habitual or change in physical activity participation and symptom severity was observed (p > 0.21). CONCLUSION: Pain onset causes a significant and immediate decrease in physical activity participation, but this change does not seem to be associated with symptom severity.