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

Development of a single retention time prediction model integrating multiple liquid chromatography systems: Application to new psychoactive substances.

Database-driven suspect screening has proven to be a useful tool to detect new psychoactive substances (NPS) outside the scope of targeted screening; however, the lack of retention times specific to a liquid chromatography (LC) system can result in a large number of false positives. A singular stream-lined, quantitative structure-retention relationship (QSRR)-based retention time prediction model integrating multiple LC systems with different elution conditions is presented using retention time data (n = 1281) from the online crowd-sourced database, HighResNPS. Modelling was performed using an artificial neural network (ANN), specifically a multi-layer perceptron (MLP), using four molecular descriptors and one-hot encoding of categorical labels. Evaluation of test set predictions (n = 193) yielded coefficient of determination (R2) and mean absolute error (MAE) values of 0.942 and 0.583 min, respectively. The model successfully differentiated between LC systems, predicting 54%, 81% and 97% of the test set within ±0.5, ±1 and ±2 min, respectively. Additionally, retention times for an analyte not previously observed by the model were predicted within ±1 min for each LC system. The developed model can be used to predict retention times for all analytes on HighResNPS for each participating laboratory's LC system to further support suspect screening

Velocity tuning of friction with two trapped atoms

Our ability to control friction remains modest, as our understanding of the underlying microscopic processes is incomplete. Atomic force experiments have provided a wealth of results on the dependence of nanofriction on structure velocity and temperature but limitations in the dynamic range, time resolution, and control at the single-atom level have hampered a description from first principles. Here, using an ion-crystal system with single-atom, single-substrate-site spatial and single-slip temporal resolution we measure the friction force over nearly five orders of magnitude in velocity, and contiguously observe four distinct regimes, while controlling temperature and dissipation. We elucidate the interplay between thermal and structural lubricity for two coupled atoms, and provide a simple explanation in terms of the Peierls–Nabarro potential. This extensive control at the atomic scale enables fundamental studies of the interaction of many-atom surfaces, possibly into the quantum regime

ICD-11 adjustment disorder: Translation and validation of the Danish International Adjustment Disorder Questionnaire among a working population of social educators

Adjustment disorder is frequently used as a diagnostic category for work-related stress disorders in Denmark. However, the diagnostic category is poorly delineated in ICD-10 which has hampered clinical practice as well as research studying the development of work-related adjustment disorders. In ICD-11, the diagnostic category of adjustment disorder has been refined and a new self-report measure is available to operationalize symptoms. The aim of the current study is to translate the International Adjustment Disorder Questionnaire (IADQ) to Danish and test the psychometric properties of the scale in a sample of social educators. A total of 609 social educators in current employment participated in an online survey including the IADQ and data was analyzed using confirmatory factor analysis. Findings suggested that a two-factor model reflecting the distinction between preoccupation and failure to adapt as part of the diagnostic criterion fitted the data best, although strong factor correlations and one cross-factor loading suggests that differentiating between the dimensions of preoccupation and failure to adapt is difficult. Relationships to burnout, posttraumatic stress and general distress support the validity of the Danish translation of the IADQ. Further research should explore the structure of adjustment disorder among other working populations

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the dopamine D-2 receptor occupancy of olanzapine in rats

A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of olanzapine in rats using the exposure (plasma and brain concentration) and D2RO profile obtained experimentally at various doses (0.01-40 mg/kg) administered by different routes. A two-compartment pharmacokinetic model was used to describe the plasma pharmacokinetic profile. A hybrid physiology- and mechanism-based model was developed to characterize the D-2 receptor binding in the striatum and was fitted sequentially to the data. The parameters were estimated using nonlinear mixed-effects modeling . Plasma, brain concentration profiles and time course of D2RO were well described by the model; validity of the proposed model is supported by good agreement between estimated association and dissociation rate constants and in vitro values from literature. This model includes both receptor binding kinetics and pharmacokinetics as the basis for the prediction of the D2RO in rats. Moreover, this modeling framework can be applied to scale the in vitro and preclinical information to clinical receptor occupancy

Perspectives on reasons for suicidal behaviour and recommendations for suicide prevention in Kenya: qualitative study

Background: Little is known about the reasons for suicidal behaviour in Africa, and communities’ perception of suicide prevention. A contextualised understanding of these reasons is important in guiding the implementation of potential suicide prevention interventions in specific settings. Aims: To understand ideas, experiences and opinions on reasons contributing to suicidal behaviour in the Coast region of Kenya, and provide recommendations for suicide prevention. Method: We conducted a qualitative study with various groups of key informants residing in the Coast region of Kenya, using in-depth interviews. Audio-recorded interviews were transcribed and translated from the local language before thematic inductive content analysis. Results: From the 25 in-depth interviews, we identified four key themes as reasons given for suicidal behaviour: interpersonal and relationship problems, financial and economic difficulties, mental health conditions and religious and cultural influences. These reasons were observed to be interrelated with each other and well-aligned to the suggested recommendations for suicide prevention. We found six key recommendations from our thematic content analysis: (a) increasing access to counselling and social support, (b) improving mental health awareness and skills training, (c) restriction of suicide means, (d) decriminalisation of suicide, (e) economic and education empowerment and (f) encouraging religion and spirituality. Conclusions: The reasons for suicidal behaviour are comparable with high-income countries, but suggested prevention strategies are more contextualised to our setting. A multifaceted approach in preventing suicide in (coastal) Kenya is warranted based on the varied reasons suggested. Community-based interventions will likely improve and increase access to suicide prevention in this study area

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