937 resultados para drug susceptibility testing
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The New South Wales (NSW) Centre for Road Safety (CRS) called for research services to conduct a review of international policy and practice to address drug-driving. The project sought to provide Transport for NSW (TfNSW) with a comprehensive review of current and emerging international practices in this area1. This report is submitted by the Centre for Accident Research and Road Safety – Queensland (CARRS-Q)...
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Alcohol-related mortality and morbidity represents a substantial financial burden on communities across the world. Adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk of acute alcoholrelated harm at least once in the previous 12 months (Australian Institute of Health and Welfare [AIHW], 2011). Excessive alcohol consumption has long been seen as a male problem; however, a gradual shift towards a social acceptance of female drunkenness has narrowed the gap in drinking quantity and style between men and women (Grucza, Bucholz, Rice, & Bierut, 2008). The presented data point to the vulnerability of women to the consequences of acute alcohol intoxication and indicate that alcohol-related offending by women is on the rise. Taken together, these findings reveal that alcohol-related harms and aggression for young women are becoming more prevalent and problematic. This report addressed these issues from a policing perspective...
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Aim: The aim of this evaluation was to evaluate the use of Individualised Medication Administration Guides (IMAGs) for patients with dysphagia on one stroke ward over a 6month period. Background: Patients with dysphagia (PWD) are more likely to suffer an administration error than patients without swallowing difficulties. To both standardise and improve medicines administration to patients with dysphagia I-MAGs were introduced on one stroke ward over a 6 month period. Methods: A software package supported with data on current national guidelines on the administration of medicines to PWD was designed by a specialised pharmacist in dysphagia to enable him to create individualised medication administration guides for patients with dysphagia which stated how each medicine should be optimally prepared and administered. On completion of the pilot service a questionnaire was given to all nurses, pharmacist and speech and language therapists who had experienced the I-MAGs. All the professionals received the same questionnaire but questions relevant only to their practice were added to the nurse’s questionnaire. Results: Of 26 Healthcare professionals (HCPs) approached, 19 returned completed questionnaires. Higher variability was found in the 13 responses from the nurse respondents than in the ones from the 3 pharmacist and the 3 SALTs. 8 (61%) of the nurses felt more confident in their practice when I-MAGs were in place. 10 (76%) of the nurses admitted that the guides could sometimes increase the time of the administration, but saw that it made practice safer. All the pharmacists considered the recommendations in the guides useful and all the respondents with the exception of one nurse (12:13) would like this service to continue. Conclusion: I-MAGs were well received on the ward and they support individualised care for patients with dysphagia. But the guides needed additional pharmacist input and greater nursing time. Research to determine the cost effectiveness of I-MAGs is needed.
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Estimating the prevalence of drink driving is a difficult task. Self‐reported drink driving indicates that drink driving is far more common than official statistics suggest. In order to promote a responsible attitude towards alcohol consumption and drink driving within the Queensland community, the Queensland Police Service, Queensland Health and Queensland Transport developed the ‘Drink Rite’ program (Queensland Police Service information sheet, 2009). However, the feasibility of the program is now in doubt as the National Health and Medical Research Council’s guidelines for alcohol consumption changed in 2009 to state “For healthy men and women, drinking no more than four standard drinks on a single occasion reduces the risk of alcohol‐related injury arising from that occasion” (NHMRC Publication, 2009, p. 51). As such, adhering to the NHMRC guidelines places restrictions on how the existing Drink Rite program can be operated (i.e. by reducing the number of standard drinks provided to participants from eight to four). It is arguable that a reduction in the number of alcoholic drinks provided to participants in the program will result in a large reduction in observed BAC readings. This, in turn, will lead to a potential loss of message content when discussing the variation in the effects of alcohol.
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Multifunctional bioactive materials with the ability to stimulate osteogenesis and angiogenesis of stem cells play an important role in the regeneration of bone defects. However, how to develop such biomaterials remains a significant challenge. In this study, we prepared mesoporous silica nanospheres (MSNs) with uniform sphere size (∼90 nm) and mesopores (∼2.7 nm), which could release silicon ions (Si) to stimulate the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) via activating their ALP activity, bone-related gene and protein (OCN, RUNX2 and OPN) expression. Hypoxia-inducing therapeutic drug, dimethyloxaloylglycine (DMOG), was effectively loaded in the mesopores of MSNs (D-MSNs). The sustained release of DMOG from D-MSNs could stabilize HIF-1α and further stimulated the angiogenic differentiation of hBMSCs as indicated by the enhanced VEGF secretion and protein expression. Our study revealed that D-MSNs could combine the stimulatory effect on both osteogenic and angiogenic activity of hBMSCs. The potential mechanism of D-MSN-stimulated osteogenesis and angiogenesis was further elucidated by the supplementation of cell culture medium with pure Si ions and DMOG. Considering the easy handling characteristics of nanospheres, the prepared D-MSNs may be applied in the forms of injectable spheres for minimally invasive surgery, or MSNs/polymer composite scaffolds for bone defect repair. The concept of delivering both stimulatory ions and functional drugs may offer a new strategy to construct a multifunctional biomaterial system for bone tissue regeneration.
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Multidrug resistance (MDR) occurs in prostate cancer, and this happens when the cancer cells resist chemotherapeutic drugs by pumping them out of the cells. MDR inhibitors such as cyclosporin A (CsA) can stop the pumping and enhance the drugs accumulated in the cells. The cellular drug accumulation is monitored using a microfluidic chip mounted on a single cell bioanalyzer. This equipment has been developed to measure accumulation of drugs such as doxorubicin (DOX) and fluorescently labeled paclitaxel (PTX) in single prostate cancer cells. The inhibition of drug efflux on the same prostate cell was examined in drug-sensitive and drug-resistant cells. Accumulation of these drug molecules was not found in the MDR cells, PC-3 RX-DT2R cells. Enhanced drug accumulation was observed only after treating the MDR cell in the presence of 5 μM of CsA as the MDR inhibitor. We envision this monitoring of the accumulation of fluorescent molecules (drug or fluorescent molecules), if conducted on single patient cancer cells, can provide information for clinical monitoring of patients undergoing chemotherapy in the future.
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Aromatherapy has been found to have some effectiveness in treating conditions such as postoperative nausea and vomiting, however unless clinicians are aware of and convinced by this evidence, it is unlikely they will choose to use it with their patients. The aim of this study was to test and modify an existing tool, Martin and Furnham’s Beliefs About Aromatherapy Scale in order to make it relevant and meaningful for use with a population of nurses and midwives working in an acute hospital setting. A Delphi process was used to modify the tool and then it was tested in a population of nurses and midwives, then exploratory factor analysis was conducted. The modified tool is reliable and valid for measuring beliefs about aromatherapy in this population.
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Many researchers in the field of civil structural health monitoring have developed and tested their methods on simple to moderately complex laboratory structures such as beams, plates, frames, and trusses. Field work has also been conducted by many researchers and practitioners on more complex operating bridges. Most laboratory structures do not adequately replicate the complexity of truss bridges. This paper presents some preliminary results of experimental modal testing and analysis of the bridge model presented in the companion paper, using the peak picking method, and compares these results with those of a simple numerical model of the structure. Three dominant modes of vibration were experimentally identified under 15 Hz. The mode shapes and order of the modes matched those of the numerical model; however, the frequencies did not match.
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While the implementation of the IEC 61850 standard has significantly enhanced the performance of communications in electrical substations, it has also increased the complexity of the system. Subsequently, these added elaborations have introduced new challenges in relation to the skills and tools required for the design, test and maintenance of 61850-compatible substations. This paper describes a practical experience of testing a protection relay using a non-conventional test equipment; in addition, it proposes a third party software technique to reveal the contents of the packets transferred on the substation network. Using this approach, the standard objects can be linked and interpreted to what the end-users normally see in the IED and test equipment proprietary software programs.
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Objective: To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease. Design Case-control study. Setting Academic research. Subject(s) The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples. Intervention(s) Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples. Main Outcome Measure(s) Allele frequency differences between cases and controls. Result(s) Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study. Conclusion(s) Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases. © 2014 by American Society for Reproductive Medicine.
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One of the objectives of this study was to evaluate soil testing equipment based on its capability of measuring in-place stiffness or modulus values. As design criteria transition from empirical to mechanistic-empirical, soil test methods and equipment that measure properties such as stiffness and modulus and how they relate to Florida materials are needed. Requirements for the selected equipment are that they be portable, cost effective, reliable, a ccurate, and repeatable. A second objective is that the selected equipment measures soil properties without the use of nuclear materials.The current device used to measure soil compaction is the nuclear density gauge (NDG). Equipment evaluated in this research included lightweight deflectometers (LWD) from different manufacturers, a dynamic cone penetrometer (DCP), a GeoGauge, a Clegg impact soil tester (CIST), a Briaud compaction device (BCD), and a seismic pavement analyzer (SPA). Evaluations were conducted over ranges of measured densities and moistures.Testing (Phases I and II) was conducted in a test box and test pits. Phase III testing was conducted on materials found on five construction projects located in the Jacksonville, Florida, area. Phase I analyses determined that the GeoGauge had the lowest overall coefficient of variance (COV). In ascending order of COV were the accelerometer-type LWD, the geophone-type LWD, the DCP, the BCD, and the SPA which had the highest overall COV. As a result, the BCD and the SPA were excluded from Phase II testing.In Phase II, measurements obtained from the selected equipment were compared to the modulus values obtained by the static plate load test (PLT), the resilient modulus (MR) from laboratory testing, and the NDG measurements. To minimize soil and moisture content variability, the single spot testing sequence was developed. At each location, test results obtained from the portable equipment under evaluation were compared to the values from adjacent NDG, PLT, and laboratory MR measurements. Correlations were developed through statistical analysis. Target values were developed for various soils for verification on similar soils that were field tested in Phase III. The single spot testing sequence also was employed in Phase III, field testing performed on A-3 and A-2-4 embankments, limerock-stabilized subgrade, limerock base, and graded aggregate base found on Florida Department of Transportation construction projects. The Phase II and Phase III results provided potential trend information for future research—specifically, data collection for in-depth statistical analysis for correlations with the laboratory MR for specific soil types under specific moisture conditions. With the collection of enough data, stronger relationships could be expected between measurements from the portable equipment and the MR values. Based on the statistical analyses and the experience gained from extensive use of the equipment, the combination of the DCP and the LWD was selected for in-place soil testing for compaction control acceptance. Test methods and developmental specifications were written for the DCP and the LWD. The developmental specifications include target values for the compaction control of embankment, subgrade, and base materials.
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Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.
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Cold water immersion and ice baths are popular methods of recovery used by athletes. From the simple wheelie bin with water and ice, to the inflatable baths with complex water cooling units to recovery sessions in the ocean, the practice of cold water immersion is wide and varied. Research into cold water immersion was conducted as early as 1963 when Clarke1 examined the influence of cold water on performance recovery after a sustained handgrip exercise. Research has been conducted to understand how cold water immersion might affect the body’s physiological systems and how factors such as water temperature and the duration of immersion might enhance recovery after training and/or competition. Despite this research activity, how are we to know if research is being put into practice? In more serious situations, where guidelines and policies need to be standardised for the safe use of a product, one would expect that there is a straight forward follow-on from research into practice. Although cold water immersion may not need the rigor of testing compared to drug treatments, for example, the decision on whether to use cold water immersion in specific situations (e.g. after training or competition) may rest with one or two of the staff associated with the athlete/team. Therefore, it would be expected that these staff are well-informed on the current literature regarding cold water immersion.
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BACKGROUND: An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients. METHODS: We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial. RESULTS: Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48). CONCLUSION: The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.