Geometric View of Measurement Errors

The slope of the best fit line from minimizing the sum of the squared oblique errors is the root of a polynomial of degree four. This geometric view of measurement errors is used to give insight into the performance of various slope estimators for the measurement error model including an adjusted fourth moment estimator introduced by Gillard and Iles (2005) to remove the jump discontinuity in the estimator of Copas (1972). The polynomial of degree four is associated with a minimun deviation estimator. A simulation study compares these estimators showing improvement in bias and mean squared error

The Photometric Autotitration of free Fatty Acids

Peer Reviewe

Neuronal and psychological underpinnings of pathological gambling

Like in the case of drugs, gambling hijacks reward circuits in a brain which is not prepared to receive such intense stimulation. Dopamine is normally released in response to reward and uncertainty in order to allow animals to stay alive in their environment – where rewards are relatively unpredictable. In this case, behavior is regulated by environmental feedbacks, leading animals to persevere or to give up. In contrast, drugs provide a direct, intense pharmacological stimulation of the dopamine system that operates independently of environmental feedbacks, and hence causes “motivational runaways”. With respect to gambling, the confined environment experienced by gamblers favors the emergence of excitatory conditioned cues, so that positive feedbacks take over negative feedbacks. Although drugs and gambling may act differently, their abnormal activation of reward circuitry generates an underestimation of negative consequences and promotes the development of addictive/compulsive behavior. In Parkinson’s and Huntington’s disease, dopamine-related therapies may disrupt these feedbacks on dopamine signalling, potentially leading to various addictions, including pathological gambling. The goal of this Research Topic is to further our understanding of the neurobiological mechanisms underlying the development of pathological gambling. This eBook contains a cross-disciplinary collection of research and review articles, ranging in scope from animal behavioral models to human imaging studies

Psychological and physiological stress and burnout among maternity providers in a rural county in Kenya: individual and situational predictors

Background: Stress and burnout among healthcare workers has been recognized as a global crisis needing urgent attention. Yet few studies have examined stress and burnout among healthcare providers in sub-Saharan Africa, and even fewer among maternity providers who work under very stressful conditions. To address these gaps, we examined self-reported stress and burnout levels as well as stress-related physiologic measures of these providers, along with their potential predictors. Methods: Participants included 101 maternity providers (62 nurses/midwives, 16 clinical officers/doctors, and 23 support staff) in western Kenya. Respondents completed Cohen’s Perceived Stress Scale, the Shirom-Melamed Burnout scale, and other sociodemographic, health, and work-related items. We also collected data on heart rate variability (HRV) and hair cortisol levels to assess stress-related physiologic responses to acute and chronic stress respectively. Multilevel linear regression models were computed to examine individual and work-related factors associated with stress, burnout, HRV, and cortisol level. Results: 85% of providers reported moderate stress and 11.5% high stress. 65% experienced low burnout and 19.6% high burnout. Average HRV (measured as the root mean square of differences in intervals between successive heart beats: RMSSD) was 60.5 (SD = 33.0) and mean cortisol was mean cortisol was 44.2 pg/mg (SD = 60.88). Greater satisfaction with life accomplishments was associated with reduced stress (β = − 2.83; CI = -5.47; − 0.18), while motivation to work excessively (over commitment) was associated with both increased stress (β = 0.61 CI: 0.19, 1.03) and burnout (β = 2.05, CI = 0.91, 3.19). Female providers had higher burnout scores compared to male providers. Support staff had higher HRV than other providers and providers under 30 years of age had higher HRV than those 30 and above. Although no association between cortisol and any predictor was statistically significant, the direction of associations was consistent with those found for stress and burnout. Conclusions: Most providers experienced moderate to high levels of stress and burnout. Individuals who were more driven to work excessively were particularly at risk for higher stress and burnout. Higher HRV of support staff and providers under age 30 suggest their more adaptive autonomic nervous system response to stress. Given its impact on provider wellbeing and quality of care, interventions to help providers manage stress are critical

The association between preschool behavioural problems and internalizing difficulties at age 10-12 years

The aim was to study the association between preschool behavioural problems and emotional symptoms in 10- to 12-year-old children. The study was based on the Aarhus Birth cohort, Denmark, and included 1,336 children. Based on the parent-administered preschool behaviour questionnaire (PBQ), we identified three not mutually exclusive preschool behavioural categories: anxious–fearful (n = 146), hyperactive–distractible (n = 98), and hostile–aggressive (n = 170). Children without any known symptoms were considered well adjusted (n = 1,000). Borderline emotional (n = 105) and emotional difficulties (n = 136) were measured at age 10–12 years with the parent-administered strength and difficulties questionnaire (SDQ). Multinomial logistic regression analyses were used to adjust for potential confounding factors. We found that anxious–fearful behaviour and hostile–aggressive preschool behaviour were associated with twice the risk of school-age emotional difficulties. Comorbidity or confounding failed to explain these results. Hyperactive–distractible preschool behaviour was not associated with school-age emotional difficulties. Preschool anxious–fearful behaviour was associated with school-age emotional difficulties, suggesting internalizing symptom stability in some children from early childhood. Preschool hostile–aggressive behaviour was also associated with school-age emotional difficulties, which suggests transformation of one behavioural dimension into another through childhood, and the need to focus on both early internalizing difficulties and hostile–aggressive behaviour as risk factors for later internalizing difficulties

Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age?

Background The objective of this study was to determine whether there was an association between mothers’ light drinking during pregnancy and risk of behavioural problems, and cognitive deficits in their children at age 3 years. Methods Data from the first two sweeps of the nationally representative prospective UK Millennium Cohort study were used. Drinking patterns during pregnancy and behavioural and cognitive outcomes were assessed during interviews and home visits. Behavioural problems were indicated by scores falling above defined clinically 15 relevant cut-offs on the parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Cognitive ability was assessed using the naming vocabulary subscale from the British Ability Scale (BAS) and the Bracken School Readiness Assessment (BSRA). Results There was a J-shaped relationship between mothers drinking 20 during pregnancy and the likelihood of high scores (above the cut-off) on the total difficulties scale of the SDQ and the conduct problems, hyperactivity and emotional symptom SDQ subscales. Children born to light drinkers were less likely to score above the cut-offs compared with children of abstinent mothers. Children 25 born to heavy drinkers were more likely to score above the cut-offs compared with children of abstinent mothers. Boys born to mothers who had up to 1–2 drinks per week or per occasion were less likely to have conduct problems (OR 0.59, 95% CI 0.45–0.77) and hyperactivity (OR 0.71, 95% CI 0.54–0.94). These effects remained 30 in fully adjusted models. Girls were less likely to have emotional symptoms (OR 0.72, 95% CI 0.51–1.01) and peer problems (OR 0.68, 95% CI 0.52–0.92) compared with those born to abstainers. These effects were attenuated in fully adjusted models. Boys born to light drinkers had higher cognitive ability test scores [standard 35 deviations, (95% CI)] BAS 0.15 (0.08–0.23) BSRA 0.24 (0.16–0.32) compared with boys born to abstainers. The difference for BAS was attenuated on adjustment for socio-economic factors, whilst the difference for BSRA remained statistically significant. Conclusions Children born to mothers who drank up to 1–2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of abstinent mothers. Heavy drinking 5 during pregnancy appears to be associated with behavioural problems and cognitive deficits in offspring at age 3 years whereas light drinking does not

relax: the analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data

Nuclear magnetic resonance (NMR) is a powerful tool for observing the motion of biomolecules at the atomic level. One technique, the analysis of relaxation dispersion phenomenon, is highly suited for studying the kinetics and thermodynamics of biological processes. Built on top of the relax computational environment for NMR dynamics is a new dispersion analysis designed to be comprehensive, accurate and easy-to-use. The software supports more models, both numeric and analytic, than current solutions. An automated protocol, available for scripting and driving the graphical user interface (GUI), is designed to simplify the analysis of dispersion data for NMR spectroscopists. Decreases in optimization time are granted by parallelization for running on computer clusters and by skipping an initial grid search by using parameters from one solution as the starting point for another —using analytic model results for the numeric models, taking advantage of model nesting, and using averaged non-clustered results for the clustered analysis. Availability and implementation: The software relax is written in Python with C modules and is released under the GPLv3+ license. Source code and precompiled binaries for all major operating systems are available from http://www.nmr-relax.com. Contact: [email protected]

relax: the analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data

International audienceNuclear Magnetic Resonance (NMR) is a powerful tool for observing the motion of biomolecules at the atomic level. One technique, the analysis of relaxation dispersion phenomenon, is highly suited for studying the kinetics and thermodynamics of biological processes. Built on top of the relax computational environment for NMR dynamics is a new dispersion analysis designed to be comprehensive, accurate and easy to use. The software supports more models, both numeric and analytic, than current solutions. An automated protocol, available for scripting and driving the GUI, is designed to simplify the analysis of dispersion data for NMR spectroscopists. Decreases in optimisation time are granted by parallelisation for running on computer clusters and by skipping an initial grid search by using parameters from one solution as the starting point for another – using analytic model results for the numeric models, taking advantage of model nesting, and using averaged non-clustered results for the clustered analysis. Availability: The software relax is written in Python with C modules and is released under the GPLv3+ licence. Source code and precompiled binaries for all major operating systems are available from http://www.nmr-relax.com

Beyond Diagnostic Accuracy: The Clinical Utility of Diagnostic Tests

Like any other medical technology or intervention, diagnostic tests should be thoroughly evaluated before their introduction into daily practice. Increasingly, decision makers, physicians, and other users of diagnostic tests request more than simple measures of a test's analytical or technical performance and diagnostic accuracy; they would also like to see testing lead to health benefits. In this last article of our series, we introduce the notion of clinical utility, which expresses-preferably in a quantitative form-to what extent diagnostic testing improves health outcomes relative to the current best alternative, which could be some other form of testing or no testing at all. In most cases, diagnostic tests improve patient outcomes by providing information that can be used to identify patients who will benefit from helpful downstream management actions, such as effective treatment in individuals with positive test results and no treatment for those with negative results. We describe how comparative randomized clinical trials can be used to estimate clinical utility. We contrast the definition of clinical utility with that of the personal utility of tests and markers. We show how diagnostic accuracy can be linked to clinical utility through an appropriate definition of the target condition in diagnostic-accuracy studies. (C) 2012 American Association for Clinical Chemistr