SimHap GUI: An intuitive graphical user interface for genetic association analysis

<p>Abstract</p> <p>Background</p> <p>Researchers wishing to conduct genetic association analysis involving single nucleotide polymorphisms (SNPs) or haplotypes are often confronted with the lack of user-friendly graphical analysis tools, requiring sophisticated statistical and informatics expertise to perform relatively straightforward tasks. Tools, such as the <it>SimHap </it>package for the R statistics language, provide the necessary statistical operations to conduct sophisticated genetic analysis, but lacks a graphical user interface that allows anyone but a professional statistician to effectively utilise the tool.</p> <p>Results</p> <p>We have developed SimHap GUI, a cross-platform integrated graphical analysis tool for conducting epidemiological, single SNP and haplotype-based association analysis. SimHap GUI features a novel workflow interface that guides the user through each logical step of the analysis process, making it accessible to both novice and advanced users. This tool provides a seamless interface to the <it>SimHap </it>R package, while providing enhanced functionality such as sophisticated data checking, automated data conversion, and real-time estimations of haplotype simulation progress.</p> <p>Conclusion</p> <p>SimHap GUI provides a novel, easy-to-use, cross-platform solution for conducting a range of genetic and non-genetic association analyses. This provides a free alternative to commercial statistics packages that is specifically designed for genetic association analysis.</p

Amplitude Reduction and Phase Shifts of Melatonin, Cortisol and Other Circadian Rhythms after a Gradual Advance of Sleep and Light Exposure in Humans

Background: The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleepwake cycle has not been fully characterized. Methodology/Principal Findings: We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity ‘room ’ light (,90–150 lux) or moderate light supplemented with bright light (,10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54 % (17–94%) and after bright light by 52 % (range 12–84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness

Sustainable Forest Management Preferences of Interest Groups in Three Regions with Different Levels of Industrial Forestry: An Exploratory Attribute-Based Choice Experiment

The challenge of sustainable forest management is to integrate diverse and sometimes conflicting management objectives. In order to achieve this goal, we need a better understanding of the aspects influencing the preferences of diverse groups and how these groups make trade-offs between different attributes of SFM. We compare the SFM preferences of interest groups in regions with different forest use histories based on the reasoning that the condition of the forest reflects the forest use history of the area. The condition of the forest also shapes an individual’s forest values and attitudes. These held values and attitudes are thought to influence SFM preferences. We tested whether the SFM preferences vary amongst the different interest groups within and across regions. We collected data from 252 persons using a choice experiment approach, where participants chose multiple times among different options described by a combination of attributes that are assigned different levels. The novelty of our approach was the use of choice experiments in the assessment of regional preference differences. Given the complexity of interregional comparison and the small sample size, this was an exploratory study based on a purposive rather than random sample. Nevertheless, our results suggest that the aggregation of preferences of all individuals within a region does not reveal all information necessary for forest management planning since opposing viewpoints could cancel each other out and lead to an interpretation that does not reflect possibly polarised views. Although based on a small\ud sample size, the preferences of interest groups within a region are generally statistically significantly different from each other; however preferences of interest groups across regions are also significantly different. This illustrates the potential importance of assessing heterogeneity by region and by group

The impact of generic-only drug benefits on patients' use of inhaled corticosteroids in a Medicare population with asthma

<p>Abstract</p> <p>Background</p> <p>Patients face increasing insurance restrictions on prescription drugs, including generic-only coverage. There are no generic inhaled corticosteroids (ICS), which are a mainstay of asthma therapy, and patients pay the full price for these drugs under generic-only policies. We examined changes in ICS use following the introduction of generic-only coverage in a Medicare Advantage population from 2003–2004.</p> <p>Methods</p> <p>Subjects were age 65+, with asthma, prior ICS use, and no chronic obstructive pulmonary disorder (n = 1,802). In 2004, 74.0% switched from having a $30 brand-copayment plan to a generic-only coverage plan (restricted coverage); 26$15–25 brand copayments in 2003–2004 (unrestricted coverage). Using linear difference-in-difference models, we examined annual changes in ICS use (measured by days-of-supply dispensed). There was a lower-cost ICS available within the study setting and we also examined changes in drug choice (higher- vs. lower-cost ICS). In multivariable models we adjusted for socio-demographic, clinical, and asthma characteristics.</p> <p>Results</p> <p>In 2003 subjects had an average of 188 days of ICS supply. Restricted compared with unrestricted coverage was associated with reductions in ICS use from 2003–2004 (-15.5 days-of-supply, 95% confidence interval (CI): -25.0 to -6.0). Among patients using higher-cost ICS drugs in 2003 (n = 662), more restricted versus unrestricted coverage subjects switched to the lower-cost ICS in 2004 (39.8% vs. 10.3%). Restricted coverage was not associated with decreased ICS use (2003–2004) among patients who switched to the lower-cost ICS (18.7 days-of-supply, CI: -27.5 to 65.0), but was among patients who did not switch (-38.6 days-of-supply, CI: -57.0 to -20.3). In addition, restricted coverage was associated with decreases in ICS use among patients with both higher- and lower-risk asthma (-15.0 days-of-supply, CI: -41.4 to 11.44; and -15.6 days-of-supply, CI: -25.8 to -5.3, respectively).</p> <p>Conclusion</p> <p>In this elderly population, patients reduced their already low ICS use in response to losing drug coverage. Switching to the lower-cost ICS mitigated reductions in use among patients who previously used higher-cost drugs. Additional work is needed to assess barriers to switching ICS drugs and the clinical effects of these drug use changes.</p

Drop-out and mood improvement: a randomised controlled trial with light exposure and physical exercise [ISRCTN36478292]

BACKGROUND: Combining bright light exposure and physical exercise may be an effective way of relieving depressive symptoms. However, relatively little is known about individual factors predicting either a good response or treatment failure. We explored background variables possibly explaining the individual variation in treatment response or failure in a randomised trial. METHODS: Participants were volunteers of working-age, free from prior mental disorders and recruited via occupational health centres. The intervention was a randomised 8-week trial with three groups: aerobics in bright light, aerobics in normal room lighting, and relaxation/stretching in bright light. Good response was defined as a 50% decrease in the symptom score on either the Hamilton Depression Rating Scale (HDRS) or 8-item scale of atypical symptoms. Background variables for the analysis included sex, age, body-mass index, general health habits, seasonal pattern, and sleep disturbances. RESULTS: Complete data were received from 98 subjects (11 men, 87 women). Of them, 42 (5 men, 37 women) were classified as responders on the HDRS. Overall, light had a significant effect on the number of responders, as assessed with the HDRS (X(2 )= .02). The number needed to treat (NNT) for light was 3.8. CONCLUSIONS: We investigated the effect of bright light and exercise on depressive symptoms. Problems with sleep, especially initial insomnia, may predict a good response to treatment using combined light and exercise. Bright light exposure and physical exercise, even in combination, seem to be well tolerated and effective on depressive symptoms

Consistency analysis of metabolic correlation networks

<p>Abstract</p> <p>Background</p> <p>Metabolic correlation networks are derived from the covariance of metabolites in replicates of metabolomics experiments. They constitute an interesting intermediate between topology (i.e. the system's architecture defined by the set of reactions between metabolites) and dynamics (i.e. the metabolic concentrations observed as fluctuations around steady-state values in the metabolic network).</p> <p>Results</p> <p>Here we analyze, how such a correlation network changes over time, and compare the relative positions of metabolites in the correlation networks with those in established metabolic networks derived from genome databases. We find that network similarity indeed decreases with an increasing time difference between these networks during a day/night course and, counter intuitively, that proximity of metabolites in the correlation network is no indicator of proximity of the metabolites in the metabolic network.</p> <p>Conclusion</p> <p>The organizing principles of correlation networks are distinct from those of metabolic reaction maps. Time courses of correlation networks may in the future prove an important data source for understanding these organizing principles.</p

Socio-demographic factors associated with smoking and smoking cessation among 426,344 pregnant women in New South Wales, Australia

BACKGROUND: This study explores the socio-demographic characteristics of pregnant women who continue to smoke during the pregnancy, and identifies the characteristics of the smokers who were likely to quit smoking during the pregnancy period. METHODS: This was secondary analysis of the New South Wales (NSW) Midwives Data Collection (MDC) 1999–2003, a surveillance system covering all births in NSW public and private hospitals, as well as home births. Bivariate and multiple logistic regression analyses were performed to explore the associations between socio-demographic characteristics and smoking behaviour during pregnancy. RESULTS: Data from 426,344 pregnant women in NSW showed that 17.0% continued to smoke during pregnancy. The smoking rate was higher among teenage mothers, those with an Aboriginal (indigenous) background, and lower among more affluent and overseas-born mothers. This study also found that unbooked confinements, and lack of antenatal care in the first trimester were strongly associated with increased risk of smoking during pregnancy. About 4.0% of the smoking women reported they may quit smoking during their pregnancy. Findings showed that mothers born overseas, of higher socio-economic status, first time mothers and those who attended antenatal care early showed an increased likelihood of smoking cessation during pregnancy. Those who were heavy smokers were less likely to quit during pregnancy. CONCLUSION: Although the prevalence of smoking during pregnancy has been declining, it remains a significant public health concern. Smoking cessation programs should target the population subgroups of women at highest risk of smoking and who are least likely to quit. Effective antismoking interventions could reduce the obstetric and perinatal complications of smoking in pregnancy

Improving medication adherence in diabetes type 2 patients through Real Time Medication Monitoring: a Randomised Controlled Trial to evaluate the effect of monitoring patients' medication use combined with short message service (SMS) reminders

Contains fulltext : 97026.pdf (publisher's version ) (Open Access)BACKGROUND: Innovative approaches are needed to support patients' adherence to drug therapy. The Real Time Medication Monitoring (RTMM) system offers real time monitoring of patients' medication use combined with short message service (SMS) reminders if patients forget to take their medication. This combination of monitoring and tailored reminders provides opportunities to improve adherence. This article describes the design of an intervention study aimed at evaluating the effect of RTMM on adherence to oral antidiabetics. METHODS/DESIGN: Randomised Controlled Trial (RCT) with two intervention arms and one control arm involving diabetes type 2 patients with suboptimal levels of adherence to oral antidiabetics (less than 80% based on pharmacy refill data). Patients in the first intervention arm use RTMM including SMS reminders and a personal webpage where they can monitor their medication use. Patients in the second intervention arm use RTMM without SMS reminders or webpage access. Patients in the control arm are not exposed to any intervention. Patients are randomly assigned to one of the three arms. The intervention lasts for six months. Pharmacy refill data of all patients are available from 11 months before, until 11 months after the start of the intervention. Primary outcome measure is adherence to oral antidiabetics calculated from: 1) data collected with RTMM, as a percentage of medication taken as prescribed, and as percentage of medication taken within the correct time interval, 2) refill data, taking the number of days for which oral antidiabetics are dispensed during the study period divided by the total number of days of the study period. Differences in adherence between the intervention groups and control group are studied using refill data. Differences in adherence between the two intervention groups are studied using RTMM data. DISCUSSION: The intervention described in this article consists of providing RTMM to patients with suboptimal adherence levels. This system combines real time monitoring of medication use with SMS reminders if medication is forgotten. If RTMM proves to be effective, it can be considered for use in various patient populations to support patients with their medication use and improve their adherence. TRIAL REGISTRATION: Netherlands Trial Register NTR1882

A prediction rule to stratify mortality risk of patients with pulmonary tuberculosis

Tuberculosis imposes high human and economic tolls, including in Europe. This study was conducted to develop a severity assessment tool for stratifying mortality risk in pulmonary tuberculosis (PTB) patients. A derivation cohort of 681 PTB cases was retrospectively reviewed to generate a model based on multiple logistic regression analysis of prognostic variables with 6-month mortality as the outcome measure. A clinical scoring system was developed and tested against a validation cohort of 103 patients. Five risk features were selected for the prediction model: hypoxemic respiratory failure (OR 4.7, 95% CI 2.8-7.9), age >= 50 years (OR 2.9, 95% CI 1.7-4.8), bilateral lung involvement (OR 2.5, 95% CI 1.44.4), >= 1 significant comorbidity-HIV infection, diabetes mellitus, liver failure or cirrhosis, congestive heart failure and chronic respiratory disease-(OR 2.3, 95% CI 1.3-3.8), and hemoglobin = 6) mortality risk. The mortality associated with each group was 2.9%, 22.9% and 53.9%, respectively. The model performed equally well in the validation cohort. We provide a new, easy-to-use clinical scoring system to identify PTB patients with high-mortality risk in settings with good healthcare access, helping clinicians to decide which patients are in need of closer medical care during treatment.This work was supported by Fundacao Amelia de Mello/Jose de Mello Saude and Sociedade Portuguesa de Pneumologia (SPP). This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). NSO is a FCT (Fundacao para a Ciencia e Tecnologia) investigator. MS is an Associate FCT Investigator. The fundershad no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Understanding the explanatory model of the patient on their medically unexplained symptoms and its implication on treatment development research: a Sri Lanka Study

<p>Abstract</p> <p>Background</p> <p>Patients with medically unexplained symptoms (MUS) are often distressed, disabled and dissatisfied with the care they receive. Illness beliefs held by patients have a major influence on the decision to consult, persistence of symptoms and the degree of disability. Illness perception models consist of frameworks to organise information from multiple sources into distinct but interrelated dimensions: identity (the illness label), cause, consequences, emotional representations perceived control and timeline.</p> <p>Our aim was to elicit the illness perceptions of patients with MUS in Sri Lankan primary care to modify and improve a CBT intervention.</p> <p>Method</p> <p>An intervention study was conducted in a hospital primary care clinic in Colombo, Sri Lanka using CBT for MUS. As a part of the baseline assessment, qualitative data was collected using; the Short Explanatory Model Interview (SEMI), from 68 patients (16–65 years) with MUS. We categorised the qualitative data in to key components of the illness perception model, to refine CBT intervention for a subsequent larger trial study.</p> <p>Results</p> <p>The cohort was chronically ill and 87% of the patients were ill for more than six months (range six months to 20 years) with 5 or more symptoms and 6 or more visits over preceding six months. A majority were unable to offer an explanation on identity (59%) or the cause (56%), but in the consequence domain 95% expressed significant illness worries; 37% believed their symptoms indicated moderately serious illness and 58% very serious illness. Reflecting emotional representation, 33% reported fear of death, 20% fear of paralysis, 13% fear of developing cancer and the rest unspecified incurable illness. Consequence and emotional domains were significant determinants of distress and consultations. Their repeated visits were to seek help to alleviate symptoms. Only a minority expected investigations (8.8 %) or diagnosis (8.8%). However, the doctors who had previously treated them allegedly concentrated more on identity than cause. The above information was used to develop simple techniques incorporating analogies to alter their perceptions</p> <p>Conclusion</p> <p>The illness perception model is useful in understanding the continued distress of patients with persistent symptoms without an underlying organic cause. Hence it can make a significant contribution when developing and evaluating culturally sensitive patient friendly interventions.</p