Extended-release ranolazine: critical evaluation of its use in stable angina.

Coronary heart disease is the major cause of morbidity and mortality throughout the world, and is responsible for approximately one of every six deaths in the US. Angina pectoris is a clinical syndrome characterized by discomfort, typically in the chest, neck, chin, or left arm, induced by physical exertion, emotional stress, or cold, and relieved by rest or nitroglycerin. The main goals of treatment of stable angina pectoris are to improve quality of life by reducing the severity and/or frequency of symptoms, to increase functional capacity, and to improve prognosis. Ranolazine is a recently developed antianginal with unique methods of action. In this paper, we review the pharmacology of ranolazine, clinical trials supporting its approval for clinical use, and studies of its quality of life benefits. We conclude that ranolazine has been shown to be a reasonable and safe option for patients who have refractory ischemic symptoms despite the use of standard medications (for example, nitrates, beta-adrenergic receptor antagonists, and calcium channel antagonists) for treatment of anginal symptoms, and also provides a modestly improved quality of life.

Associations between smoking behavior-related alleles and the risk of melanoma.

Several studies have reported that cigarette smoking is inversely associated with the risk of melanoma. This study further tested whether incorporating genetic factors will provide another level of evaluation of mechanisms underlying the association between smoking and risk of melanoma. We investigated the association between SNPs selected from genome-wide association studies (GWAS) on smoking behaviors and risk of melanoma using 2,298 melanoma cases and 6,654 controls. Among 16 SNPs, three (rs16969968 [A], rs1051730 [A] and rs2036534 [C] in the 15q25.1 region) reached significance for association with melanoma risk in men (0.01 < = P values < = 0.02; 0.85 < = Odds Ratios (ORs) <= 1.20). There was association between the genetic scores based on the number of smoking behavior-risk alleles and melanoma risk with P-trend = 0.005 among HPFS. Further association with smoking behaviors indicating those three SNPs (rs16969968 [A], rs1051730 [A] and rs2036534 [C]) significantly associated with number of cigarettes smoked per day, CPD, with P = 0.009, 0.011 and 0.001 respectively. The SNPs rs215605 in the PDE1C gene and rs6265 in the BDNF gene significantly interacted with smoking status on melanoma risk (interaction P = 0.005 and P = 0.003 respectively). Our study suggests that smoking behavior-related SNPs are likely to play a role in melanoma development and the potential public health importance of polymorphisms in the CHRNA5-A3-B4 gene cluster. Further larger studies are warranted to validate the findings.

Sex offender risk assessment and management in Ireland

This research examined sex offender risk assessment and management in Ireland. It focused on the statutory agencies with primary responsibility (Garda Síochána and the Probation Service). The goal was to document the historical, contextual and current systems, in addition to identifying areas of concern/improvements. The research was a mixed-methods approach. Eight studies were conducted. This incorporated documentary reviews of four Commission to Inquire Reports, qualitative interviews/focus groups with Garda staff, Probation Service staff, statutory agencies, community stakeholders, various Non-Governmental Organisations (NGOs) and sex offenders. Quantitative questionnaires were also administered to Garda staff. In all over 70 interviews were conducted and questionnaires were forwarded to 270 Garda members. The overall findings are: •Sex offender management in Ireland has become formal only since 2001. Knowledge, skills and expertise is in its infancy and is still evolving. •Mixed reviews and questions regarding fitness for purpose of currently used risk assessments tools were noted. •The Sex Offender Act 2001 requires additional elements to ensure safe sex offender monitoring and public protection. A judicial review of the Sex Offender Act 2001 was recommended by many respondents. •Interagency working under SORAM was hugely welcomed. The sharing of information has been welcomed by managing agencies as the key benefit to improving sex offender management. •Respondents reported that in practice, sex offender management in Ireland is fragmented and unevenly implemented. The research concluded that an independent National Sex Offender Authority should be established as an oversight and regulatory body for policy, strategy and direction in sex offender management. Further areas of research were also highlighted: ongoing evaluation and audits of the joint agency process and systems in place; recidivism studies tracking the risk assessment ratings and subsequent offending; and an evaluation of the current status of sex offender housing in Ireland.

Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.

An Ergonomic Evaluation of a Wrist Brace for Canadian Tree Planters

Tree planting is one of the most physically demanding occupations in Canada and as a result, tree planters are at an elevated risk of injury, specifically at the wrist. Wrist injuries develop on account of the highly repetitive nature of the job, as well as other musculoskeletal risk factors including non-neutral wrist postures and high impact forces sustained at the wrist during shovel-ground impact. As a result, wrist brace use has become common among planters, in an effort to limit deviated wrist postures while also providing enhanced stability at the wrist. The external stability provided by a wrist brace is thought to reduce the muscular effort required to provide stiffness at the wrist during shovel-ground impact. Since these prospective benefits have not been formally investigated, the purpose of this study was to determine the effect of a wrist brace on wrist posture, muscle activity, and joint rotational stiffness about the wrist joint (for two degrees of freedom: flexion/extension and ulnar/radial deviation). We hypothesized that the brace would promote more neutrally aligned wrist angles, and that muscle activity and joint rotational stiffness would also decrease when participants wore the brace. Fourteen tree planters with at least one season of experience were recruited to complete two planting conditions in a laboratory setting: one condition while wearing the brace (with brace, WB) and one condition without the brace (no brace, NB). The results from this study showed that at shovel-ground impact muscle activity trended towards increasing in three muscles when participants wore the brace. Additionally, wrist angles improved about the flexion/extension axis of rotation while increasing in deviation about the ulnar/radial axis of rotation when participants wore the brace. Joint rotational stiffness increased when participants wore the wrist brace. Participants from this study indicated difficulty gripping the shovel due to the bulk of the wrist brace, and this feature is discussed with possible suggestions for future iterations of design. In addition to grip diameter this analysis also prompts the suggestion that hand length and experience should also be considered in the design of tree planting tools, specifically an ergonomic aid such as a wrist brace.

Evaluation and Testing of a Lightweight Fine Aggregate Concrete Bridge Deck in Buchanan County, Iowa, TR-648, 2016

Internal curing is a relatively new technique being used to promote hydration of Portland cement concretes. The fundamental concept is to provide reservoirs of water within the matrix such that the water does not increase the initial water/cementitious materials ratio to the mixture, but is available to help continue hydration once the system starts to dry out. The reservoirs used in the US are typically in the form of lightweight fine aggregate (LWFA) that is saturated prior to batching. Considerable work has been conducted both in the laboratory and in the field to confirm that this approach is fundamentally sound and yet practical for construction purposes. A number of bridge decks have been successfully constructed around the US, including one in Iowa in 2013. It is reported that inclusion of about 20% to 30% LWFA will not only improve strength development and potential durability, but, more importantly, will significantly reduce shrinking, thus reducing cracking risk. The aim of this work was to investigate the feasibility of such an approach in a bridge deck.

Virtual Clinical Trials in PET Imaging for Improved Diagnosis of and Evaluation of Therapies for Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

Risk Prediction In Cardiovascular Epidemiology: Considerations for Modeling Composite Endpoints

Thesis (Master's)--University of Washington, 2016-08

Evaluation of Mobile Telephone Text Message Reminders for People with Antipsychotic Medication

Nonadherence to treatment is a worldwide problem among people with severe mental disorders. Patient treatment adherence may be supported with simple reminding methods e.g. text message reminders. However, there is limited evidence of its benefits. Intervention evaluation is essential in mHealth research. Therefore, this evaluative study was conducted. This study aimed to evaluate text message reminder use in encouraging patients’treatment adherence among people with antipsychotic medication. The data were collected between September 2011 and December 2013. First, a systematic literature review revealed that text message reminders were widely used in healthcare. However, its impacts were conflicting. Second, a sub-sample (n = 562) analysis showed that patients preferred humorous text message reminders and preferred to receive them in the morning, at the beginning of the week. Age, gender and marital status seemed to have different effects on the preferred amount and timing of the selected reminders. Third, a cross-sectional survey revealed that people with antipsychotic medication (n = 408) expressed overall satisfaction towards the reminder system. Finally, the evaluative design showed that patient recruitment for a randomized controlled trial concerning people with antipsychotic medication was challenging due to low rates of eligible participants. Follow-up drop-out rates varied depending on the data collection method. Participants’ demographic characteristics were associated with the risk of dropping out from the trial. This study suggests that text messages are a potential reminder system in healthcare services among people with antipsychotic medication. More research is needed to gain a comprehensive picture of the impacts and effectiveness of text message reminders.

The Use of Multi-Criteria Decision Analysis in Performing Alternatives Assessment and Comparative Risk Analysis: The Case Study of Codling Moth Pesticides

Thesis (Ph.D.)--University of Washington, 2016-08

Evaluation of Community-led Complementary Feeding and Learning Sessions

Thesis (Master's)--University of Washington, 2016-08

Field Evaluation of a Competitive Lateral-flow Assay for Detection of Alternaria brassicae in Vegetable Brassica Crops

On-site detection of inoculum of polycyclic plant pathogens could potentially contribute to management of disease outbreaks. A 6-min, in-field competitive immunochromatographic lateral flow device (CLFD) assay was developed for detection of Alternaria brassicae (the cause of dark leaf spot in brassica crops) in air sampled above the crop canopy. Visual recording of the test result by eye provides a detection threshold of approximately 50 dark leaf spot conidia. Assessment using a portable reader improved test sensitivity. In combination with a weather-driven infection model, CLFD assays were evaluated as part of an in-field risk assessment to identify periods when brassica crops were at risk from A. brassicae infection. The weather-driven model overpredicted A. brassicae infection. An automated 7-day multivial cyclone air sampler combined with a daily in-field CLFD assay detected A. brassicae conidia air samples from above the crops. Integration of information from an in-field detection system (CLFD) with weather-driven mathematical models predicting pathogen infection have the potential for use within disease management systems.

Exercise and Lifestyle Therapy Improves Weight Maintenance in Young People With Psychosis: A Service Evaluation

INTRODUCTION Young people with psychosis typically have higher rates of premature cardiovascular disease and metabolic disorders compared to non-psychotic peers. This has been primarily due to a sedentary lifestyle, poor diet composition, misuse of harmful substances and higher rates of obesity and smoking. When prescribed obesogenic antipsychotic medication, a weight gain of >12 kg within 2 years is typical. PURPOSE: To examine the benefits of a 12 wk exercise and lifestyle intervention entitled ‘Supporting Health and Promoting Exercise’ (SHAPE) for young people recently diagnosed with psychosis. METHODS Participants (n=26; 8 females; mean age 27.7 ± 5.1) engaged in weekly 45’ education sessions on healthy lifestyle behaviors, including: managing anxiety and depression, mindfulness and relaxation training, substance misuse, smoking cessation, healthy eating and nutritional advice, dental and sexual health care. This was followed by a 45’ exercise session including activities such as circuit and resistance training, yoga, and badminton, led by qualified exercise instructors. Anthropometric data were measured at baseline, 12 wk and 12 month post-intervention. Lifestyle behaviors and clinical measurements, including resting heart rate, blood pressure, total cholesterol, triglycerides, HbA1c and prolactin, were assessed at baseline and 12 months post-intervention as part of their routine clinical care plan. Significant differences over time were assessed using Paired Sample t-tests. RESULTS SHAPE participants (n=26) presented with first episode psychosis (n=11), schizophrenia (n=11), bipolar disorder (n=2), at risk mental state (n=1), and persistent delusion disorder (n=1) of which 52% were prescribed highly obesogenic antipsychotic medications (Clozapine and Olanzepine). Mean baseline data suggests participants were at an increased health risk due to elevated values in mean BMI (70% were overweight or obese), waist circumference, resting heart rate, and triglycerides (see Table 1 & 2). Over 50% reported smoking daily and 85% had elevated resting blood pressure (>120/80 mm Hg). At 12 wk post-intervention, no changes were observed in mean BMI or waist circumference (see Table 1); 19 participants either maintained (mean 0.5 kg: range ± 2 kg) or decreased (mean -5.7 kg: range 2-7 kg) weight; 7 participants increased weight (mean 4.9 kg: range 2.0-9.6 kg). At 12 month post-intervention (n=16), no change was evident in mean BMI, waist circumference, or any other clinical variable (see Table 2). Positive impacts on lifestyle behaviors included 7 participants eating ~400g of fruit/vegetables daily, 2 ceased substance use, 2 ceased alcohol use, 4 ceased smoking and 5 were less sedentary. CONCLUSION At the start of the programme, participants were already at an increased risk for cardiometabolic disorders. Findings suggest that SHAPE supported young people with psychosis to: -attenuate their physical health risk following a 12 wk exercise and lifestyle intervention which were sustained at 12 months follow up. -make positive lifestyle behavior changes leading to sustained improvements in weight maintenance and physical health.

Decision making models embedded into a web-based tool for assessing pest infestation risk

Current practices in agricultural management involve the application of rules and techniques to ensure high quality and environmentally friendly production. Based on their experience, agricultural technicians and farmers make critical decisions affecting crop growth while considering several interwoven agricultural, technological, environmental, legal and economic factors. In this context, decision support systems and the knowledge models that support them, enable the incorporation of valuable experience into software systems providing support to agricultural technicians to make rapid and effective decisions for efficient crop growth. Pest control is an important issue in agricultural management due to crop yield reductions caused by pests and it involves expert knowledge. This paper presents a formalisation of the pest control problem and the workflow followed by agricultural technicians and farmers in integrated pest management, the crop production strategy that combines different practices for growing healthy crops whilst minimising pesticide use. A generic decision schema for estimating infestation risk of a given pest on a given crop is defined and it acts as a metamodel for the maintenance and extension of the knowledge embedded in a pest management decision support system which is also presented. This software tool has been implemented by integrating a rule-based tool into web-based architecture. Evaluation from validity and usability perspectives concluded that both agricultural technicians and farmers considered it a useful tool in pest control, particularly for training new technicians and inexperienced farmers.

An evaluation of carbon offset supplementation options for beef production systems on coastal speargrass in central Queensland, Australia

In 2014, the Australian Government implemented the Emissions Reduction Fund to offer incentives for businesses to reduce greenhouse gas (GHG) emissions by following approved methods. Beef cattle businesses in northern Australia can participate by applying the 'reducing GHG emissions by feeding nitrates to beef cattle' methodology and the 'beef cattle herd management' methods. The nitrate (NO3) method requires that each baseline area must demonstrate a history of urea use. Projects earn Australian carbon credit units (ACCU) for reducing enteric methane emissions by substituting NO3 for urea at the same amount of fed nitrogen. NO3 must be fed in the form of a lick block because most operations do not have labour or equipment to manage daily supplementation. NO3 concentrations, after a 2-week adaptation period, must not exceed 50 g NO3/adult animal equivalent per day or 7 g NO3/kg dry matter intake per day to reduce the risk of NO3 toxicity. There is also a 'beef cattle herd management' method, approved in 2015, that covers activities that improve the herd emission intensity (emissions per unit of product sold) through change in the diet or management. The present study was conducted to compare the required ACCU or supplement prices for a 2% return on capital when feeding a low or high supplement concentration to breeding stock of either (1) urea, (2) three different forms of NO3 or (3) cottonseed meal (CSM), at N concentrations equivalent to 25 or 50 g urea/animal equivalent, to fasten steer entry to a feedlot (backgrounding), in a typical breeder herd on the coastal speargrass land types in central Queensland. Monte Carlo simulations were run using the software @risk, with probability functions used for (1) urea, NO3 and CSM prices, (2) GHG mitigation, (3) livestock prices and (4) carbon price. Increasing the weight of steers at a set turnoff month by feeding CSM was found to be the most cost-effective option, with or without including the offset income. The required ACCU prices for a 2% return on capital were an order of magnitude higher than were indicative carbon prices in 2015 for the three forms of NO3. The likely costs of participating in ERF projects would reduce the return on capital for all mitigation options. © CSIRO 2016.