875 resultados para Tight and adherence junctions
Resumo:
Background: The overuse of antibiotics is becoming an increasing concern. Antibiotic resistance, which increases both the burden of disease, and the cost of health services, is perhaps the most profound impact of antibiotics overuse. Attempts have been made to develop instruments to measure the psychosocial constructs underlying antibiotics use, however, none of these instruments have undergone thorough psychometric validation. This study evaluates the psychometric properties of the Parental Perceptions on Antibiotics (PAPA) scales. The PAPA scales attempt to measure the factors influencing parental use of antibiotics in children. Methods: 1111 parents of children younger than 12 years old were recruited from primary schools’ parental meetings in the Eastern Province of Saudi Arabia from September 2012 to January 2013. The structure of the PAPA instrument was validated using Confirmatory Factor Analysis (CFA) with measurement model fit evaluated using the raw and scaled χ2, Goodness of Fit Index, and Root Mean Square Error of Approximation. Results: A five-factor model was confirmed with the model showing good fit. Constructs in the model include: Knowledge and Beliefs, Behaviors, Sources of information, Adherence, and Awareness about antibiotics resistance. The instrument was shown to have good internal consistency, and good discriminant and convergent validity. Conclusion: The availability of an instrument able to measure the psychosocial factors underlying antibiotics usage allows the risk factors underlying antibiotic use and overuse to now be investigated.
Resumo:
We describe a short signature scheme that is strongly existentially unforgeable under an adaptive chosen message attack in the standard security model. Our construction works in groups equipped with an efficient bilinear map, or, more generally, an algorithm for the Decision Diffie-Hellman problem. The security of our scheme depends on a new intractability assumption we call Strong Diffie-Hellman (SDH), by analogy to the Strong RSA assumption with which it shares many properties. Signature generation in our system is fast and the resulting signatures are as short as DSA signatures for comparable security. We give a tight reduction proving that our scheme is secure in any group in which the SDH assumption holds, without relying on the random oracle model.
Resumo:
Purpose To review and update the evidence relating to the personal, social, and environmental factors associated with physical activity (PA) in adults. Methods Systematic review of the peer-reviewed literature to identify papers published between 1998 and 2000 with PA (and including exercise and exercise adherence). Qualitative reports or case studies were not included. Results Thirty-eight new studies were located. Most confirmed the existence of factors already known to be correlates of PA. Changes in status were noted in relation to the influence of marital status, obesity, smoking, lack of time, past exercise behavior, and eight environmental variables. New studies were located which focused on previously understudied population groups such as minorities, middle and older aged adults, and the disabled. Conclusion The newly reported studies tend to take a broader “ecological” approach to understanding the correlates of PA and are more focused on environmental factors. There remains a need to better understand environmental influences and the factors that influence different types of PA. As most of the work in this field still relies on cross-sectional studies, longitudinal and intervention studies will be required if causal relationships are to be inferred.
Resumo:
Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.
Resumo:
Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within these tumours is used for prognosis and selection of therapies, there is a continuing need for additional markers to be identified. A considerable amount of current literature, based predominantly on cell culture systems, suggests that a major mechanism responsible for the progression of breast cancer is due to tumour cells losing their epithelial features and gaining mesenchymal properties. These events are proposed to be very similar to the epithelial-mesenchymal transition (EMT) process that has been well characterised in embryonic development. For the developmental and putative cancer EMT, the cell intermediate filament status changes from a keratin-rich network which connects to adherens junctions and hemidesmosomes, to a vimentin-rich network connecting to focal adhesions. This review summarises observations of vimentin expression in breast cancer model systems, and discusses the potential role of EMT in human breast cancer progression, and the prognostic usefulness of vimentin expression.
Resumo:
Lymphoedema following cancer treatment is characterized by swelling, and adversely influences mobility, function and quality of life. There is no cure, but without treatment lymphedema may progress. Since lymphedema treatment options are costly and time consuming, understanding the influence of these, and other potential barriers, on treatment adherence is vital in reducing the public health burden of lymphedema. Complex physical therapy and compression are supported by scientific evidence and patients also perceive these treatments as effective for improving symptoms and function. Multiple treatments may be required to treat all aspects of the condition. Patients and health professionals should consider effect and costs when identifying optimal treatment strategies.
Resumo:
Two in vitro and two in vivo assays for the study of human cancer invasion and metastasis are described. The assays include in vitro invasiveness through an artificial basement membrane (Matrigel®), invasiveness and metastasis in nude mice of subcutaneously injected LacZ-transduced human tumor cells, in vitro adherence to basement membrane components, and LacZ-transduced human cancer cells injected intravenously into nude mice. In studies of the processes involved in human cancer cell invasion and metastasis, these four assays were found to be complementary, and thus provide a set of test systems for preclinical screening of agents which interfere with these processes.
Resumo:
В статье представлено развитие принципа построения автоматической пилотажно-навигационной системы (АПНС) для беспилотного летательного аппарата (БЛА). Принцип заключается в синтезе комплексных систем управления БПЛА не только на основе использования алгоритмов БИНС, но и алгоритмов, объединяющих в себе решение задач формирования и отработки сформированной траектории резервированной системой управления и навигации. Приведены результаты аналитического исследования и данные летных экспериментов разработанных алгоритмов АПНС БЛА, обеспечивающих дополнительное резервирование алгоритмов навигации и наделяющих БЛА новым функциональной способностью по выходу в заданную точку пространства с заданной скоростью в заданный момент времени с учетом атмосферных ветровых возмущений. Предложена и испытана методика идентификации параметров воздушной атмосферы: направления и скорости W ветра. Данные летных испытаний полученного решения задачи терминальной навигации демонстрируют устойчивую работу синтезированных алгоритмов управления в различных метеоусловиях. The article presents a progress in principle of development of automatic navigation management system (ANMS) for small unmanned aerial vehicle (UAV). The principle defines a development of integrated control systems for UAV based on tight coupling of strap down inertial navigation system algorithms and algorithms of redundant flight management system to form and control flight trajectory. The results of the research and flight testing of the developed ANMS UAV algorithms are presented. The system demonstrates advanced functional redundancy of UAV guidance. The system enables new UAV capability to perform autonomous multidimensional navigation along waypoints with controlled speed and time of arrival taking into account wind. The paper describes the technique for real-time identification of atmosphere parameters such as wind direction and wind speed. The flight test results demonstrate robustness of the algorithms in diverse meteorological conditions.
Resumo:
The refereed papers contained in this volume of conference proceedings were among those presented at the 2nd International Conference on Crime, Justice and Social Democracy, hosted by the Crime and Justice Research Centre, Faculty of Law, QUT, from 8 – 11 July 2013. The conference attracted an impressive list of speakers from Australasia, Europe, North America and Latin America. These seven papers can be viewed at the Crime and Justice Research Centre’s website at http://crimejusticeconference.com/publications/ as can Volume 1 representing another 26 selected papers from the conference. As with the papers contained in the first volume, this set of papers raises important questions about the links between crime, justice and social democracy, and continues the contribution that the Crime and Justice Research Centre makes towards engaging with these topics. We thank all those who submitted papers for review for this second volume of proceedings, as well as the peer reviewers for taking the time to review the papers, often within very tight timelines.
Resumo:
• The doctrine of double effect is an exception to the general rule that taking active steps that end life is unlawful. • The essence of the doctrine at common law is intention. • Hastening a patient’s death through palliative care will be lawful provided the primary intention is to relieve pain, and not cause death, even if that death is foreseen. • Some States have enacted legislative excuses that deal with the provision of palliative care. • These statutory excuses tend to be stricter than the common law as they impose other requirements in addition to having an appropriate intent, such as adherence to some level of recognised medical practice.
Resumo:
This paper provides a three-layered framework to monitor the positioning performance requirements of Real-time Relative Positioning (RRP) systems of the Cooperative Intelligent Transport Systems (C-ITS) that support Cooperative Collision Warning (CCW) applications. These applications exploit state data of surrounding vehicles obtained solely from the Global Positioning System (GPS) and Dedicated Short-Range Communications (DSRC) units without using other sensors. To this end, the paper argues the need for the GPS/DSRC-based RRP systems to have an autonomous monitoring mechanism, since the operation of CCW applications is meant to augment safety on roads. The advantages of autonomous integrity monitoring are essential and integral to any safety-of-life system. The autonomous integrity monitoring framework proposed necessitates the RRP systems to detect/predict the unavailability of their sub-systems and of the integrity monitoring module itself, and, if available, to account for effects of data link delays and breakages of DSRC links, as well as of faulty measurement sources of GPS and/or integrated augmentation positioning systems, before the information used for safety warnings/alarms becomes unavailable, unreliable, inaccurate or misleading. Hence, a monitoring framework using a tight integration and correlation approach is proposed for instantaneous reliability assessment of the RRP systems. Ultimately, using the proposed framework, the RRP systems will provide timely alerts to users when the RRP solutions cannot be trusted or used for the intended operation.
Resumo:
Background Adherence to evidence based medicines in patients who have experienced a myocardial infarction remains low. Individual’s beliefs towards their medicines are a strong predictor of adherence and may influence other factors that impact on adherence. Objective To investigate if community pharmacists discussing patients’ beliefs about their medicines improved medication adherence at 12 months post myocardial infarction. Setting This study included 200 patients discharged from a public teaching hospital in Queensland, Australia, following a myocardial infarction. Patients were randomised into intervention (n = 100) and control groups (n = 100) and followed for 12 months. Method All patients were interviewed between 5 to 6 weeks, at 6 and 12 months post discharge by the researcher using the repertory grid technique. This technique was used to elicit the patient’s individualised beliefs about their medicines for their myocardial infarction. In the intervention group, patients’ beliefs about their medicines were communicated by the researcher to their community pharmacist. The pharmacist used this information to tailor their discussion with the patient about their medication beliefs at designated time points (3 and 6 months post discharge). The control group was provided with usual care. Main outcome measure The difference in non-adherence measured using a medication possession ratio between the intervention and control groups at 12 months post myocardial infarction. Results There were 137 patients remaining in the study (intervention group n = 72, control group n = 65) at 12 months. In the intervention group 29 % (n = 20) of patients were non-adherent compared to 25 % (n = 16) of patients in control group. Conclusion Discussing patients’ beliefs about their medicines for their myocardial infarction did not improve medication adherence. Further research on patients beliefs should focus on targeting non-adherent patients whose reasons for their non-adherence is driven by their medication beliefs.
Resumo:
Approximate Bayesian Computation’ (ABC) represents a powerful methodology for the analysis of complex stochastic systems for which the likelihood of the observed data under an arbitrary set of input parameters may be entirely intractable – the latter condition rendering useless the standard machinery of tractable likelihood-based, Bayesian statistical inference [e.g. conventional Markov chain Monte Carlo (MCMC) simulation]. In this paper, we demonstrate the potential of ABC for astronomical model analysis by application to a case study in the morphological transformation of high-redshift galaxies. To this end, we develop, first, a stochastic model for the competing processes of merging and secular evolution in the early Universe, and secondly, through an ABC-based comparison against the observed demographics of massive (Mgal > 1011 M⊙) galaxies (at 1.5 < z < 3) in the Cosmic Assembly Near-IR Deep Extragalatic Legacy Survey (CANDELS)/Extended Groth Strip (EGS) data set we derive posterior probability densities for the key parameters of this model. The ‘Sequential Monte Carlo’ implementation of ABC exhibited herein, featuring both a self-generating target sequence and self-refining MCMC kernel, is amongst the most efficient of contemporary approaches to this important statistical algorithm. We highlight as well through our chosen case study the value of careful summary statistic selection, and demonstrate two modern strategies for assessment and optimization in this regard. Ultimately, our ABC analysis of the high-redshift morphological mix returns tight constraints on the evolving merger rate in the early Universe and favours major merging (with disc survival or rapid reformation) over secular evolution as the mechanism most responsible for building up the first generation of bulges in early-type discs.
Resumo:
Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI.
Resumo:
Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infection (UTI) in the developed world. The major factors associated with virulence of UPEC are fimbrial adhesins, which mediate specific attachment to host receptors and trigger innate host responses. Another group of adhesins is represented by the autotransporter (AT) subgroup of proteins. The genome-sequenced prototype UPEC strain CFT073 contains 11 putative AT-encoding genes. In this study, we have performed a detailed molecular characterization of two closely related AT adhesins from CFT073: UpaB (c0426) and UpaC (c0478). PCR screening revealed that the upaB and upaC AT-encoding genes are common in E. coli. The upaB and upaC genes were cloned and characterized in a recombinant E. coli K-12 strain background. This revealed that they encode proteins located at the cell surface but possess different functional properties: UpaB mediates adherence to several ECM proteins, while UpaC expression is associated with increased biofilm formation. In CFT073, upaB is expressed while upaC is transcriptionally repressed by the global regulator H-NS. In competitive colonization experiments employing the mouse UTI model, CFT073 significantly outcompeted its upaB (but not upaC) isogenic mutant strain in the bladder. This attenuated phenotype was also observed in single-challenge experiments, where deletion of the upaB gene in CFT073 significantly reduced early colonization of the bladder.