644 research outputs found
Validity and responsiveness to change of the Active Australia Survey according to gender, age, BMI, education, and physical activity level and awareness
© 2019 The Author(s). Background: This study aimed to investigate the validity of the Active Australia Survey across different subgroups and its responsiveness to change, as few previous studies have examined this. Methods: The Active Australia Survey was validated against the ActiGraph as an objective measure of physical activity. Participants (n = 465) wore the ActiGraph for 7 days and subsequently completed the Active Australia Survey. Moderate activity, vigorous activity and total moderate and vigorous physical activity were compared using Spearman rank-order correlations. Changes in physical activity between baseline and 3-month assessments were correlated to examine responsiveness to change. The data were stratified to assess outcomes according to different subgroups (e.g., gender, age, weight, activity levels). Results: With regards to the validity, a significant correlation of ρ = 0.19 was found for moderate physical activity, ρ = 0.33 for vigorous physical activity and ρ = 0.23 for moderate and vigorous physical activity combined. For vigorous physical activity correlations were higher than 0.3 for most subgroups, whereas they were only higher than 0.3 in those with a healthy weight for the other activity outcomes. With regards to responsiveness to change, a correlation of ρ = 0.32 was found for moderate physical activity, ρ = 0.19 for vigorous physical activity and ρ = 0.35 for moderate and vigorous physical activity combined. For moderate and vigorous activity combined correlations were higher than 0.4 for several subgroups, but never for vigorous physical activity. Conclusions: Little evidence for the validity of Active Australia Survey was found, although the responsiveness to change was acceptable for several subgroups. Findings from studies using the Active Australia Survey should be interpreted with caution. Trial registration: World Health Organisation Universal Trial Number: U111-1119-1755. Australian New Zealand Clinical Trials Registry, ACTRN12611000157976. Registration date: 8 March 2011
Helping someone with problem drug use: a delphi consensus study of consumers, carers, and clinicians
<p>Abstract</p> <p>Background</p> <p>Problem use of illicit drugs (i.e. drug abuse or dependence) is associated with considerable health and social harms, highlighting the need for early intervention and engagement with health services. Family members, friends and colleagues play an important role in supporting and assisting individuals with problem drug use to seek professional help, however there are conflicting views about how and when such support should be offered. This paper reports on the development of mental health first aid guidelines for problem drug use in adults, to help inform community members on how to assist someone developing problem drug use or experiencing a drug-related crisis.</p> <p>Methods</p> <p>A systematic review of the scientific and lay literature was conducted to develop a 228-item survey containing potential first-aid strategies to help someone developing a drug problem or experiencing a drug-related crisis. Three panels of experts (29 consumers, 31 carers and 27 clinicians) were recruited from Australia, Canada, New Zealand, the United Kingdom, and the United States. Panel members independently rated the items over three rounds, with strategies reaching consensus on importance written into the guidelines.</p> <p>Results</p> <p>The overall response rate across three rounds was 80% (86% consumers, 81% carers, 74% clinicians). 140 first aid strategies were endorsed as essential or important by 80% or more of panel members. The endorsed strategies provide information and advice on what is problem drug use and its consequences, how to approach a person about their problem drug use, tips for effective communication, what to do if the person is unwilling to change their drug use, what to do if the person does (or does not) want professional help, what are drug-affected states and how to deal with them, how to deal with adverse reactions leading to a medical emergency, and what to do if the person is aggressive.</p> <p>Conclusions</p> <p>The guidelines provide a consensus-based resource for community members who want to help someone with a drug problem. It is hoped that the guidelines will lead to better support and understanding for those with problem drug use and facilitate engagement with professional help.</p
Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors
The shortcomings of current direct-acting anti-viral therapy against human cytomegalovirus (HCMV) has led to interest in host-directed therapy. Here we re-examine the use of interferon proteins to inhibit HCMV replication utilizing both high and low passage strains of HCMV. Pre-treatment of cells with interferon alpha (IFNα) was required for robust and prolonged inhibition of both low and high passage HCMV strains, with no obvious toxicity, and was associated with an increased anti-viral state in HCMV-infected cells. Pre-treatment of cells with IFNα led to poor expression of HCMV immediate-early proteins from both high and low passage strains, which was associated with the presence of the anti-viral factor SUMO-PML. Inhibition of HCMV replication in the presence of IFNα involving ZAP proteins was HCMV strain-dependent, wherein a high passage HCMV strain was obviously restricted by ZAP and a low passage strain was not. This suggested that strain-specific combinations of anti-viral factors were involved in inhibition of HCMV replication in the presence of IFNα. Overall, this work further supports the development of strategies involving IFNα that may be useful to inhibit HCMV replication and highlights the complexity of the anti-viral response to HCMV in the presence of IFNα
Allelic Exchange of Pheromones and Their Receptors Reprograms Sexual Identity in Cryptococcus neoformans
Cell type specification is a fundamental process that all cells must carry out to ensure appropriate behaviors in response to environmental stimuli. In fungi, cell identity is critical for defining “sexes” known as mating types and is controlled by components of mating type (MAT) loci. MAT–encoded genes function to define sexes via two distinct paradigms: 1) by controlling transcription of components common to both sexes, or 2) by expressing specially encoded factors (pheromones and their receptors) that differ between mating types. The human fungal pathogen Cryptococcus neoformans has two mating types (a and α) that are specified by an extremely unusual MAT locus. The complex architecture of this locus makes it impossible to predict which paradigm governs mating type. To identify the mechanism by which the C. neoformans sexes are determined, we created strains in which the pheromone and pheromone receptor from one mating type (a) replaced the pheromone and pheromone receptor of the other (α). We discovered that these “αa” cells effectively adopt a new mating type (that of a cells); they sense and respond to α factor, they elicit a mating response from α cells, and they fuse with α cells. In addition, αa cells lose the α cell type-specific response to pheromone and do not form germ tubes, instead remaining spherical like a cells. Finally, we discovered that exogenous expression of the diploid/dikaryon-specific transcription factor Sxi2a could then promote complete sexual development in crosses between α and αa strains. These data reveal that cell identity in C. neoformans is controlled fully by three kinds of MAT–encoded proteins: pheromones, pheromone receptors, and homeodomain proteins. Our findings establish the mechanisms for maintenance of distinct cell types and subsequent developmental behaviors in this unusual human fungal pathogen
Helping someone with problem drinking: Mental health first aid guidelines - a Delphi expert consensus study
Background Alcohol is a leading risk factor for avoidable disease burden. Research suggests that a drinker's social network can play an integral role in addressing hazardous (i.e., high-risk) or problem drinking. Often however, social networks do not have adequate mental health literacy (i.e., knowledge about mental health problems, like problem drinking, or how to treat them). This is a concern as the response that a drinker receives from their social network can have a substantial impact on their willingness to seek help. This paper describes the development of mental health first aid guidelines that inform community members on how to help someone who may have, or may be developing, a drinking problem (i.e., alcohol abuse or dependence). Methods A systematic review of the research and lay literature was conducted to develop a 285-item survey containing strategies on how to help someone who may have, or may be developing, a drinking problem. Two panels of experts (consumers/carers and clinicians) individually rated survey items, using a Delphi process. Surveys were completed online or via postal mail. Participants were 99 consumers, carers and clinicians with experience or expertise in problem drinking from Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. Items that reached consensus on importance were retained and written into guidelines. Results The overall response rate across all three rounds was 68.7% (67.6% consumers/carers, 69.2% clinicians), with 184 first aid strategies rated as essential or important by ≥80% of panel members. The endorsed guidelines provide guidance on how to: recognize problem drinking; approach someone if there is concern about their drinking; support the person to change their drinking; respond if they are unwilling to change their drinking; facilitate professional help seeking and respond if professional help is refused; and manage an alcohol-related medical emergency. Conclusion The guidelines provide a consensus-based resource for community members seeking to help someone with a drinking problem. Improving community awareness and understanding of how to identify and support someone with a drinking problem may lead to earlier recognition of problem drinking and greater facilitation of professional help seeking
Design, analysis, and feedback control of a nonlinear micro-piezoelectric–electrostatic energy harvester
A nonlinear micro-piezoelectric–electrostatic energy harvester is designed and studied using mathematical and computational methods. The system consists of a cantilever beam substrate, a bimorph piezoelectric transducer, a pair of tuning parallel-plate capacitors, and a tip–mass. The governing nonlinear mathematical model of the electro-mechanical system including nonlinear material and quadratic air-damping is derived for the series connection of the piezoelectric layers. The static and modal frequency curves are computed to optimize the operating point, and a parametric study is performed using numerical methods. A bias DC voltage is used to adapt the system to resonate with respect to the frequency of external vibration. Furthermore, to improve the bandwidth and performance of the harvester (and achieve a high level of harvested power without sacrificing the bandwidth), a nonlinear feedback loop is integrated into the design
Pre-ejection period by radial artery tonometry supplements echo doppler findings during biventricular pacemaker optimization
<p>Abstract</p> <p>Background</p> <p>Biventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.</p> <p>Methods</p> <p>Blinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 ± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 ± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.</p> <p>Results</p> <p>Significant improvement post optimization was achieved in LV ET (286.9 ± 37.3 to 299 ± 34.6 ms, p < 0.001), LV VTI (15.9 ± 4.8 cm to 18.4 ± 5.1 cm, p < 0.001) and MPI (0.57 ± 0.2 to 0.45 ± 0.13, p < 0.001) and in PEP (246.7 ± 36.1 ms to 234.7 ± 35.5 ms, p = 0.003), PEP/ET (0.88 ± 0.21 to 0.79 ± 0.17, p < 0.001), and PEP/VTI (17.3 ± 7 to 13.78 ± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 ± 0.8 to 2.0 ± 0.9 (p = 0.004) at 1.8 ± 1.4 months.</p> <p>Conclusion</p> <p>An acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.</p
Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling
BACKGROUND: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1–4 status for further clarification of the differing roles for the HER family at a biological level. METHODS: Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (T(pot)). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1–4 status in 55 patients from the BrdU cohort. RESULTS: We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low T(pot )times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. CONCLUSIONS: These results support the hypothesis that HER1–3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role
The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family
The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future
Effect of Smoke-Free Legislation on Adult Smoking Behaviour in England in the 18 Months following Implementation
Comprehensive smoke-free legislation covering all enclosed public places and workplaces was implemented in England on 1 July 2007. This study examines the impact of this legislation on smoking prevalence, number of cigarettes smoked and location of smoking, controlling for secular trends through the end of 2008.Repeat cross sectional survey using nationally representative data from the Health Survey for England (HSE). In total there are 54,333 respondents from 2003-2008. Logit and linear regression models were used to examine the effect of the legislation on smoking prevalence and the number of cigarettes smoked daily among continuing smokers which took the underlying trend into account. Our finding suggest that smoking prevalence (current smoker) decreased from 25% in 2003 to 21% in 2008 (AOR = 0.96 per year, 95% CI = 0.95-0.98, P<0.01) and the mean number of cigarettes consumed daily by smokers decreased from 14.1 in 2003 to 13.1 in 2008 (coefficient for time trend = -0.28±0.06 SE cig/day per year, P<0.01). After adjusting for these trends the introduction of smoke-free legislation was not associated with additional reductions in smoking prevalence (AOR = 1.02, 95% CI = 0.94-1.11, P = 0.596) or daily cigarette use in smokers (0.42±0.28 SE; P = 0.142). The percentage of respondents reporting smoking 'at work' and 'inside pubs or bars' decreased significantly from 14% to 2% (p<0.001) and from 34% to 2% (p<0.001), respectively, after the legislation. The percentage reporting smoking 'inside restaurants, cafes, or canteens' decreased significantly from 9% to 1% (p<0.001) and 'inside their home' decreased significantly from 65% to 55% (p<0.01).There is widespread compliance with the smoke-free legislation in England, which has led to large drops in indoor smoking in all venues, including at home. Declines in smoking prevalence and consumption continued along existing trends; they did not accelerate during the 18 months immediately following implementation
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