Robust Bayesian sensitivity analysis for case-control studies with uncertain exposure misclassification probabilities

Exposure misclassification in case–control studies leads to bias in odds ratio estimates. There has been considerable interest recently to account for misclassification in estimation so as to adjust for bias as well as more accurately quantify uncertainty. These methods require users to elicit suitable values or prior distributions for the misclassification probabilities. In the event where exposure misclassification is highly uncertain, these methods are of limited use, because the resulting posterior uncertainty intervals tend to be too wide to be informative. Posterior inference also becomes very dependent on the subjectively elicited prior distribution. In this paper, we propose an alternative “robust Bayesian” approach, where instead of eliciting prior distributions for the misclassification probabilities, a feasible region is given. The extrema of posterior inference within the region are sought using an inequality constrained optimization algorithm. This method enables sensitivity analyses to be conducted in a useful way as we do not need to restrict all of our unknown parameters to fixed values, but can instead consider ranges of values at a time.published_or_final_versio

Characterization of a Low-Cost Optical Flow Sensor When Using an External Laser as a Direct Illumination Source

In this paper, a low cost optical flow sensor is combined with an external laser device to measure surface displacements and mechanical oscillations. The measurement system is based on applying coherent light to a diffuser surface and using an optical flow sensor to analyze the reflected and transferred light to estimate the displacement of the surface or the laser spot. This work is focused on the characterization of this measurement system, which can have the optical flow sensor placed at different angles and distances from the diffuser surface. The results have shown that the displacement of the diffuser surface is badly estimated when the optical mouse sensor is placed in front of the diffuser surface (angular orientation >150°) while the highest sensitivity is obtained when the sensor is located behind the diffuser surface and on the axis of the laser source (angular orientation 0°). In this case, the coefficient of determination of the measured displacement, R2, was very high (>0.99) with a relative error of less than 1.29%. Increasing the distance between the surface and the sensor also increased the sensitivity which increases linearly, R2 = 0.99. Finally, this measurement setup was proposed to measure very low frequency mechanical oscillations applied to the laser device, up to 0.01 Hz in this work. The results have shown that increasing the distance between the surface and the optical flow sensor also increases the sensitivity and the measurement range

Diagnosis and aetiology of congenital muscular dystrophy: we are halfway there

OBJECTIVES: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and Next Generation Sequencing (NGS) technologies. METHODS: 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS. RESULTS: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin α2, α-dystroglycan or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39/123). Of 85 patients presenting in the last 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43/85). The diagnoses within the cohort were heterogeneous. 45/59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11/59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome and two had microdeletions. Within the cohort, five patients had variants in novel (PIGY and GMPPB) or recently published genes (GFPT1 and MICU1) and seven had variants in TTN or RYR1; large genes that are technically difficult to Sanger sequence. INTERPRETATION: These data support NGS as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second-tier investigation. This article is protected by copyright. All rights reserved

Smoking and alcohol behaviours in people following hip and knee arthroplasty: data from the Osteoarthritis Initiative

Background: Smoking and alcohol consumption have a negative effect on overall health. Limited evidence has been presented as to how these health behaviours may change between pre- and postoperative intervals in the initial 12 months post-arthroplasty. The purpose of this study was to address this uncertainty.  Hypothesis: Smoking and alcohol consumption differs between pre- and post-THA/TKA and is differs between non-arthroplasty cohorts.  Materials and Methods: Data from the Osteoarthritis Initiative (OAI), a population-based observational study in the USA, was gathered. In total, data from 287 people who had undergone THA or TKA from baseline to Month 48 OAI follow-up assessments were analysed. Data on this cohort were compared to 287 age- and gender-matched people with osteoarthritis. Mean change from pre- to post-arthroplasty, and differences between arthroplasty and non-arthroplasty participants for smoking and alcohol consumption were assessed descriptively and through Wilcoxin-matched pairs test and Student t-tests (as appropriate),.  Results: The life-time prevalence of smoking was high for people who received THA (99%) and TKA (96%). Prevalence of current smoking significantly decreased from 5% to 3% across the THA and TKA cohort in the initial 12 months post-arthroplasty (p<0.05). Similarly, there was a statistically significant decrease in weekly alcohol consumption post-arthroplasty for people who underwent THA and TKA (p<0.01), although the mean difference was only by 0.9 alcoholic drinks. The only statistically significant difference in smoking and alcohol consumption for arthroplasty to non-arthroplasty participants was in weekly alcohol consumption, which was higher by 0.3 drinks in the non-arthroplasty cohort (p=0.04).  Conclusions: Smoking and alcohol consumption decreased in the initial 12 months post-THA and TKA. This was not significantly different to an age- and gender-matched non-arthroplasty cohort. Whilst this is positive, a small group of patients still present with unhealthy lifestyle choices in relation to these behaviours post-arthroplasty

Benzodiazepine use of community-based violent offenders : a preliminary investigation

Objective: To explore the relationship between benzodiazepine use and violent crime in a sample of community-based offenders. Methods: Participants were recruited via drug diversion and treatment programs in Melbourne, Australia. Data regarding benzodiazepine and other substance use, mental health, personality characteristics, and crime involvement was collected through semi-structured interviews conducted in 2011. Participants (n = 82, 79.3% male) were 21-56 years old, predominantly Australian-born (89%), with 14.6% identifying as Aboriginal or Torres Strait Islanders. Eligibility criteria were having been charged with a criminal offence in the previous six months and at least monthly benzodiazepine use. Group differences between violent (n = 11) and non-violent offenders were assessed via independent samples t-tests (two-tailed) and non-parametric tests. Results: Individuals charged with violent index offences were significantly more likely to use higher average doses of alprazolam (p = .040), and exhibit benzodiazepine dependence (p = .037) as well as report high levels of sensation seeking, prior violence, and the diagnoses of depression and personality disorder, than individuals charged with non-violent index offences. Conclusions: The findings suggest the existence of a complex dynamic between mental health and violent offending that may be influenced by benzodiazepine use, in particular alprazolam. A core implication of these preliminary findings includes attending to the interpersonal skills and adaptive coping resources of violent offenders. Key words: benzodiazepines, alprazolam, violence, impulsive behaviour, mental healt

An instrument to measure job satisfaction of nursing home administrators

BACKGROUND: The psychometric properties of the nursing home administrator job satisfaction questionnaire (NHA-JSQ) are presented, and the steps used to develop this instrument. METHODS: The NHA-JSQ subscales were developed from pilot survey activities with 93 administrators, content analysis, and a research panel. The resulting survey was sent to 1,000 nursing home administrators. Factor analyses were used to determine the psychometric properties of the instrument. RESULTS: Of the 1,000 surveys mailed, 721 usable surveys were returned (72 percent response rate). The factor analyses show that the items were representative of six underlying factors (i.e., coworkers, work demands, work content, work load, work skills, and rewards). CONCLUSION: The NHA-JSQ represents a short, psychometrically sound job satisfaction instrument for use in nursing homes

A poisson regression approach for modelling spatial autocorrelation between geographically referenced observations

Abstract Background Analytic methods commonly used in epidemiology do not account for spatial correlation between observations. In regression analyses, omission of that autocorrelation can bias parameter estimates and yield incorrect standard error estimates. Methods We used age standardised incidence ratios (SIRs) of esophageal cancer (EC) from the Babol cancer registry from 2001 to 2005, and extracted socioeconomic indices from the Statistical Centre of Iran. The following models for SIR were used: (1) Poisson regression with agglomeration-specific nonspatial random effects; (2) Poisson regression with agglomeration-specific spatial random effects. Distance-based and neighbourhood-based autocorrelation structures were used for defining the spatial random effects and a pseudolikelihood approach was applied to estimate model parameters. The Bayesian information criterion (BIC), Akaike's information criterion (AIC) and adjusted pseudo R2, were used for model comparison. Results A Gaussian semivariogram with an effective range of 225 km best fit spatial autocorrelation in agglomeration-level EC incidence. The Moran's I index was greater than its expected value indicating systematic geographical clustering of EC. The distance-based and neighbourhood-based Poisson regression estimates were generally similar. When residual spatial dependence was modelled, point and interval estimates of covariate effects were different to those obtained from the nonspatial Poisson model. Conclusions The spatial pattern evident in the EC SIR and the observation that point estimates and standard errors differed depending on the modelling approach indicate the importance of accounting for residual spatial correlation in analyses of EC incidence in the Caspian region of Iran. Our results also illustrate that spatial smoothing must be applied with care.</p

A Balanced Translocation in Kallmann Syndrome Implicates a Long Noncoding RNA, RMST, as a GnRH Neuronal Regulator.

CONTEXT: Kallmann syndrome (KS) is a rare, genetically heterogeneous Mendelian disorder. Structural defects in KS patients have helped define the genetic architecture of gonadotropin-releasing hormone (GnRH) neuronal development in this condition. OBJECTIVE: Examine the functional role a novel structural defect affecting a long noncoding RNA (lncRNA), RMST, found in a KS patient. DESIGN: Whole genome sequencing, induced pluripotent stem cells and derived neural crest cells (NCC) from the KS patient were contrasted with controls. SETTING: The Harvard Reproductive Sciences Center, Massachusetts General Hospital Center for Genomic Medicine, and Singapore Genome Institute. PATIENT: A KS patient with a unique translocation, t(7;12)(q22;q24). INTERVENTIONS/MAIN OUTCOME MEASURE/RESULTS: A novel translocation was detected affecting the lncRNA, RMST, on chromosome 12 in the absence of any other KS mutations. Compared with controls, the patient's induced pluripotent stem cells and NCC provided functional information regarding RMST. Whereas RMST expression increased during NCC differentiation in controls, it was substantially reduced in the KS patient's NCC coincident with abrogated NCC morphological development and abnormal expression of several "downstream" genes essential for GnRH ontogeny (SOX2, PAX3, CHD7, TUBB3, and MKRN3). Additionally, an intronic single nucleotide polymorphism in RMST was significantly implicated in a genome-wide association study associated with age of menarche. CONCLUSIONS: A novel deletion in RMST implicates the loss of function of a lncRNA as a unique cause of KS and suggests it plays a critical role in the ontogeny of GnRH neurons and puberty