Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.
- MeSH
- Adult MeSH
- Electroencephalography MeSH
- Electrocorticography MeSH
- Gamma Rhythm physiology MeSH
- Humans MeSH
- Brain Mapping methods MeSH
- Young Adult MeSH
- Brain physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Nowadays, advanced computational chemistry methods offer various strategies for revealing prospective hit structures in drug development essentially through accurate binding free energy predictions. After the era of molecular docking and quantitative structure-activity relationships, much interest has been lately oriented to perturbed molecular dynamic approaches like replica exchange with solute tempering and free energy perturbation (REST/FEP) and the potential of the mean force with adaptive biasing and accelerated weight histograms (PMF/AWH). Both of these receptor-based techniques can exploit exascale CPU&GPU supercomputers to achieve high throughput performance. In this fundamental study, we have compared the predictive power of a panel of supercomputerized molecular modelling methods to distinguish the major binding modes and the corresponding binding free energies of a promising tacrine related potential antialzheimerics in human acetylcholinesterase. The binding free energies were estimated using flexible molecular docking, molecular mechanics/generalized Born surface area/Poisson-Boltzmann surface area (MM/GBSA/PBSA), transmutation REST/FEP with 12 x 5 ns/λ windows, annihilation FEP with 20 x 5 ns/λ steps, PMF with weight histogram analysis method (WHAM) and 40 x 5 ns samples, and PMF/AWH with 10 x 100 ns replicas. Confrontation of the classical approaches such as canonical molecular dynamics and molecular docking with alchemical calculations and steered molecular dynamics enabled us to show how large errors in ΔG predictions can be expected if these in silico methods are employed in the elucidation of a common case of enzyme inhibition.Communicated by Ramaswamy H. Sarma.
Practically all experimental measurements related to the response of nonlinear bodies that are made within a purely mechanical context are concerned with inhomogeneous deformations, though, in many experiments, much effort is taken to engender homogeneous deformation fields. However, in experiments that are carried out in vivo, one cannot control the nature of the deformation. The quantity of interest is the deformation gradient and/or its invariants. The deformation gradient is estimated by tracking positions of a finite number of markers placed in the body. Any experimental data-reduction procedure based on tracking a finite number of markers will, for a general inhomogeneous deformation, introduce an error in the determination of the deformation gradient, even in the idealized case, when the positions of the markers are measured with no error. In our study, we are interested in a quantitative description of the difference between the true gradient and its estimate obtained by tracking the markers, that is, in the quantitative description of the induced error due to the data reduction. We derive a rigorous upper bound on the error, and we discuss what factors influence the error bound and the actual error itself. Finally, we illustrate the results by studying a practically interesting model problem. We show that different choices of the tracked markers can lead to substantially different estimates of the deformation gradient and its invariants. It is alarming that even qualitative features of the material under consideration, such as the incompressibility of the body, can be evaluated differently with different choices of the tracked markers. We also demonstrate that the derived error estimate can be used as a tool for choosing the appropriate marker set that leads to the deformation gradient estimate with the least guaranteed error.
- MeSH
- Models, Biological * MeSH
- Biomechanical Phenomena MeSH
- Biomedical Engineering * MeSH
- Humans MeSH
- Mathematical Concepts MeSH
- Stress, Mechanical MeSH
- Nonlinear Dynamics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In this paper, linearized approximations of both the forward and the inverse problems of resonant ultrasound spectroscopy for the determination of mechanical properties of thin surface layers are presented. The linear relations between the frequency shifts induced by the deposition of the layer and the in-plane elastic coefficients of the layer are derived and inverted, the applicability range of the obtained linear model is discussed by a comparison with nonlinear models and finite element method (FEM), and an algorithm for the estimation of experimental errors in the inversely determined elastic coefficients is described. In the final part of the paper, the linearized inverse procedure is applied to evaluate elastic coefficients of a 310 nm thick diamond-like carbon layer deposited on a silicon substrate.
- MeSH
- Diagnostic Errors MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Mental Disorders diagnosis MeSH
- Humans MeSH
- Adolescent MeSH
- Drug-Related Side Effects and Adverse Reactions diagnosis MeSH
- Family Relations MeSH
- Schizophrenia diagnosis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
INTRODUCTION: Amphetamine-type stimulants (ATS) including amphetamine, methylenedioxymethamphetamine/'ecstasy', methamphetamine, synthetic cathinones and 'Ritalin' are the second most commonly used illicit drugs globally. Yet, there is little evidence on which factors are associated with the development of different patterns of ATS use over the life course. This study aims to examine which individual, social and environmental factors shape different pathways and trajectories of ATS consumption. The study will be conducted in five European countries: Germany, the Netherlands, Poland, Czech Republic and the UK. METHODS AND ANALYSIS: We will use a sequential mixed-methods study design to investigate the multiple factors (familial, social and occupational situation, critical life events, general risk behaviour, mental and physical health, satisfaction with life) that shape individual ATS use pathways. A systematic literature review will be performed to provide an overview of the current academic literature on the topic. In module 1, qualitative semistructured interviews (n=ATS users and non-users) will be conducted to explore individual experiences of, and perspectives on, dynamics of change in stimulant consumption patterns. In module 2, structured questionnaires (n=2000 ATS users and non-users) will be administered via tablet computers to validate and enhance the generalisability of the interview findings. Data integration will take place at two key points. First, during the study, where the findings from the first qualitative interviews will inform the design of the structured questionnaire. Second, at the end of the study, where mixed methods data will be brought together to generate an in-depth, contextualised understanding of the research topic. ETHICS AND DISSEMINATION: The study has been approved by the respective responsible ethics committee in each participating country. Data will be treated confidentially to ensure participants' anonymity. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings for policy and practice.
- MeSH
- Risk Assessment MeSH
- Humans MeSH
- Multicenter Studies as Topic MeSH
- Substance-Related Disorders epidemiology psychology MeSH
- Risk Factors MeSH
- Central Nervous System Stimulants administration & dosage MeSH
- Systematic Reviews as Topic MeSH
- Research Design * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
... Willis -- 3 The Dynamics of Cognitive Interviewing 45 -- Paul Beatty -- 4 Data Quality in Cognitive Interviews ... ... Smit -- 7 Response Latency and (Para)Linguistic Expressions as Indicators of Response Error 131 -- Stasja ... ... Questionnaires 209 -- Roger Tourangeau -- PART IV STATISTICAL MODELING -- 12 Modeling Measurement Error ... ... MULTIMETHOD APPLICATIONS -- 23 A Multiple-Method Approach to Improving the Clarity of -- Closely Related ...
Wiley series in survey methodology
1st ed. xvi, 606 s.
At the present time proximal femoral fractures account for 30% of all fractures referred to hospitals for treatment. Our population is ageing, the proportion of patients with post-menopausal or senile osteoporosis is increasing and therefore the number of proximal femoral fractures requiring urgent treatment is growing too. In the age category of 50 years and older, the incidence of these fractures has increased exponentially. Our department serves as a trauma centre for half of Prague and part of the Central Bohemia Region with a population of 1 150 000. Prague in particular has a high number of elderly citizens. Our experience is based on extensive clinical data obtained from the Register of Proximal Femoral Fractures established in 1997. During 14 years, 4280 patients, 3112 women and 1168 men, were admitted to our department for treatment of proximal femoral fractures. All patients were followed up until healing or development of complications. In the group understudy, 82% were patients older than 70 years; 72% of those requiring surgery were in their seventies and eighties. Men were significantly younger than women (p<0.001) and represented 30% of the group. The fractures were 2.3-times more frequent in women than in men. In the category under 60 years, men significantly outnumbered women (p<0.001). The patients with pertrochanteric fractures were, on the average, eight years older than the patients with intertrochanteric fractures, which is a significant difference (p<0.001). The mortality rate within a year of injury was about 30%. Trochanteric fractures accounted for 54.7% and femoral neck fractures for 45.3% of all fractures. The inter-annual increase was 5.9%, with more trochanteric than femoral neck fractures. There was a non-significant decrease in intertrochanteric (AO 31-A3) fractures. On the other hand, the number of pertrochanteric (AO 31-A1+2) fractures increased significantly (p<0.001). A total of 1 394 fractures were treated with a proximal femoral nail; a short nail was used in 1260 and a long nail in 134 of them. A dynamic hip screw (DHS) was employed to treat 947 fractures. Distinguishing between pertrochanteric (21-A1, 31-A2) and intertrochanteric (31 -A3) fractures is considered an important approach because of their different behaviour at reduction. Pertrochanteric fractures occurred more frequently (81.5%); the patients' age was higher (80 years on the average) and women outnumbered men at a ratio of 3:1. Intertrochanteric fractures were found in significantly younger patients (average, 72 years), with a women-to-men ratio of 1.3:1. Stable pertrochanteric fractures (31-A1) were preferably indicated for DHS surgery. Unstable pertrochanteric (31-A2) and intertrochanteric (31-A3) fractures were treated with a nail. The patients underwent surgery on the day of injury or the next day. In the case of contraindications to an urgent intervention, surgery was performed after the patient's medical condition had stabilised. The number of complications was largely related to technical errors, such as insufficient reduction or an incorrectly inserted implant. Intertrochanteric fractures were associated with a higher occurrence of complications. No implant can compensate for errors due to surgery. Serious complications can be reduced by the correct assessment of fracture type, the use of an appropriate operative technique and early treatment of potential complications. The necessity of restoring continuity in the medial cortex of the femoral neck (Adams' arch) is the requirement that should be observed. Pseudoarthrosis or varus malalignment in a healed hip should be managed by valgus osteotomy. When the femoral head or the acetabulum is damaged, total hip arthroplasty is indicated. A prerequisite for successful surgical outcome is urgently and correctly performed osteosynthesis allowing for early rehabilitation and mobilisation of the patient
- MeSH
- Splints utilization MeSH
- Hip Fractures * epidemiology surgery classification MeSH
- Fracture Fixation, Intramedullary * methods MeSH
- Bone Screws utilization MeSH
- Hip Prosthesis utilization MeSH
- Humans MeSH
- Postoperative Complications * etiology MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Review MeSH
Attitudes and practices of truth-telling to people with cancer have shifted substantially in the past few years. However, cultural and individual differences persist, and some difficulties common to all medical specialties are magnified in oncology. In this Personal View, I review and analyse data for attitudes and practices of truth-telling worldwide. I also assess ethical justifications, with special reference to interpersonal aspects of patients' autonomy and the dynamic nature of truth in the clinical context. Examples are provided to show how this ethical perspective can help oncologists to frame the discourse on truth-telling and to find solutions to the dilemmas of whether, when, and how to tell the truth to their patients in clinical practice. Finally, I identify future targets for research.
