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Dispositional impulsivity in normal and abnormal samples.

Impulsive behaviors, which can include aggression, substance use and suicide, are common and core features of the DSM Axis II Cluster B personality disorders. The construct of dispositional impulsivity is multidimensional and a number of self-report measures have been created to represent features of this trait (e.g., novelty seeking, behavioral disinhibition, nonplanning). Because these questionnaires are rarely administered together in the same sample, little is known about how they are related to one another. The current study was conducted to examine the structure of dimensional impulsive personality traits in a large normative sample (n=351). Analyses revealed that dispositional impulsivity was represented by three moderately correlated latent factors labeled thrill seeking, nonplanning and disinhibited behavior. Confirmatory factor analyses were also used to examine the extent to which the internal structure of these impulsive personality traits was similar in a sample defined as abnormal (i.e., DSM-III-R Cluster B PD diagnoses; n=70). Results revealed that the structure of these traits was consistent across the two samples in a model that constrained factor loadings and structural covariances (NFI=0.89; CFI=95; RMSEA=0.04). In addition, correlational relationships between the impulsivity factor scores and behavioral and sociodemographic factors (e.g., socioeconomic status, substance use) were consistent across the two samples. These results help to establish a common framework for understanding the multidimensional nature of impulsivity. Results from these analyses also lend support to a large body of work that demonstrates that normal and abnormal personality features are related.

Aggression↗

Low-probability event-detection and separation via statistical wavelet thresholding: an application to psychophysiological denoising.

OBJECTIVES: The aim of this paper is to introduce and test a general, wavelet-based method for the automatic removal of noise and artefact from psychophysiological data. METHODS: Statistical wavelet thresholding (SWT) performs blind source separation by transforming data to the wavelet domain, and subsequent filtering of wavelet coefficients based on a statistical framework. The observed wavelet coefficients are modelled using a Gaussian distribution, from which low-probability outliers are attenuated based on their z-scores. RESULTS: The technique was applied to both simulated and real event-related potentials (ERP) data. SWT applied to artificial data displayed increased signal-to-noise ratio (SNR) improvements as noise amplitude increased. ERP averages of filtered experimental data displayed a correlation of 0.93 with operator-filtered data, compared with a correlation of 0.56 for unfiltered data. The energy of operator-designated contaminated trials was attenuated by a factor of 7.46 relative to uncontaminated trials. SNR improvement was observed in simulated tests. CONCLUSIONS: Variations of SWT may be useful in situations where one wishes to separate uncommon/uncharacteristic structures from time series data sets. For artefact removal applications, SWT appears to be a valid alternative to expert operator screening.

Artifacts↗

Type A behavior, nonverbal expressive style, and health.

Understanding the precise nature of the links among styles of behavior, emotional expression, and the development of heart disease is a major challenge in psychology and health. In the present research, 60 men at high risk for coronary heart disease were examined in terms of their expressive style, their specific nonverbal cues, their personality, and their health. As assessed by the self-report Jenkins Activity Survey (JAS; Jenkins, Zyzanski, & Rosenman, 1979), half the men were Type A and half were Type B. To provide a more refined grouping, the men were further classified on the basis of scores on the Affective Communication Test (ACT; H. S. Friedman, Prince, Riggio, & DiMatteo, 1980), a self-report measure of nonverbal expressiveness. In the framework of theory and research on nonverbal expressive style, videotapes of the men were extensively rated and coded in terms of their judged appearance, the actual audio and video nonverbal cues emitted, and the words said (transcript). Two groups of Type A individuals were found--one that was repressed, tense, and illness-prone, but another that was healthy, talkative, in control, and charismatic. Furthermore, in addition to the expected healthy Type B men, a subgroup of Type B men was found who were submissive, repressed, tense, have an external locus of control, and may be illness-prone. A refined conception of the Type A behavior pattern is deemed necessary in light of these findings. Implications for improving the validity of the Type A construct and understanding the link between psychosocial factors and disease are discussed.

Adult↗

Clinical evaluation of language functions (CELF) diagnostic battery: an analysis and critique.

To summarize, the main strengths of the CELF are the clarity with which the manual describes the subtests and the instructions provided for test administration. Major concerns center on the absence of a theoretical framework as a basis for the selection of language skills assessed, the use of only "normal" children in the standardization sample, the lack of scoring criteria for one subtest, the seemingly incorrect weighting system for another, and minimal evidence of test reliability and validity.

Adolescent↗

Evaluation of likelihood ratios for complex genetic models.

Although methods for computing likelihoods for simple genetic models on large and complex pedigrees have been known for some time, and although methods for evaluating likelihoods for complex genetic models on small pedigrees have likewise been well known, likelihood evaluation for complex models given data on extended pedigrees has remained an intractable problem. The Gibbs sampler provides a method of Monte Carlo evaluation of likelihood ratios for complex models on extended and/or complex pedigrees. With increasing computer speeds, this approach provides a tractable and efficient approach to many such likelihood evaluation problems in linkage and segregation analysis. In this paper, however, the authors restrict attention to two basic building-blocks of the overall process. The first is the sequential computation of Gaussian likelihoods for multiple random-effects models on extended pedigrees. The second is the use of this in the Monte Carlo evaluation of likelihoods for the classical mixed model of segregation analysis. The implementation of the Gibbs sampler on pedigrees that permits this Monte Carlo evaluation is detailed. An example is then presented, and finally, in the context of this same example, it is also shown how linkage analysis for a quantitative trait falls within this same framework.

Female↗

Predictive evolutionary genomics: principles, validation, and practice.

Climate change and habitat loss are driving rapid evolutionary responses in populations world-wide, which creates an urgent need for evolutionary forecasting in conservation and agriculture. Such forecasting can be categorized into three time scales: trait-based models that use multivariate quantitative genetic equations to project correlated phenotypic responses up to c. 20 generations, allele-based analyses that model allele frequency dynamics up to 100 generations, and composite adaptation scores that aggregate many small effects to yield predictions across longer horizons. However, these approaches have remained largely disconnected. Here, we present a Bayesian framework that integrates these three complementary approaches for evolutionary prediction. Our framework combines genomic, phenotypic, and environmental data to yield probabilistic predictions with explicit uncertainty. We show how predictive evolutionary forecasts can be validated with experimental evolution, field experimentation, historical specimens, and reciprocal transplants. These validated forecasts can help advance conservation and agricultural programmes by helping predict which populations are at risk of future extinction, optimizing breeding programmes for future climates, and planning ecosystem management under environmental change. By supporting a shift towards more predictive approaches in evolutionary biology, this framework may help improve our ability to manage biodiversity and food security in a changing world.

Genomics↗

Development of the Leapfrog methodology for evaluating hospital implemented inpatient computerized physician order entry systems.

The 1999 Institute of Medicine report raised public awareness of the frequency and cost of adverse drug events in medicine. In response, in November 2000 a coalition of healthcare purchasers announced the formation of the Leapfrog Group, an organization dedicated to making "great leaps forward" in the safety and quality of health care in America. Their first target-computerized physician order entry (CPOE)-was selected specifically for its potential to reduce harm to patients from medications. The Leapfrog inpatient CPOE standard included a requirement that the organization operating CPOE should demonstrate via a test that their inpatient CPOE system can alert physicians to at least 50% of common serious prescribing errors. This paper outlines the development of this test which evaluates the ability of implemented CPOE systems to prevent the occurrence of medication errors that have a high likelihood of leading to adverse drug events. A framework was developed to include 12 different categories of CPOE based decision support that could prevent prescribing errors leading to adverse drug events. A scoring system was developed based on the known frequency and severity of adverse drug events. Simulated test patients and accompanying simulated test medication orders were developed to evaluate the ability of a CPOE system to intercept prescribing errors in all 12 decision support categories. The test was validated at a number of inpatient sites using both commercially available and custom developed CPOE systems. A web based application was developed to allow hospitals to self-administer the evaluation.

Certification↗

Benchmarking physician performance, part 2.

Part 1 of this article (January-February 2006) reviewed ways of measuring the work of physicians through methods such as data envelopment analysis (DEA) and relative value units (RVUs). These techniques provide insights into: 1. Who are the best-performing physicians? 2. Who are the underperforming physicians? 3. How can underperforming physicians improve? 4. What are the underperformers' performance targets? 5. How do you deal with full- and part-time physicians in a university setting? Part 2 compares the performance of 16 primary care physicians in the same medical specialty using DEA efficiency scores. DEA is capable of modeling multiple criteria and automatically determines the relative weights of each performance measure. This research also provides a preliminary framework for how work measurement and DEA can be used as a basis for a medical team or physician compensation system.

Benchmarking↗

Sibling adaptation to childhood cancer collaborative study: prevalence of sibling distress and definition of adaptation levels.

A multisite collaborative study assessed the frequency and intensity of emotional/behavioral distress in siblings of children with cancer. A sample of 254 siblings, aged 4 to 18 years, and their parents completed interviews and self-report measures 6 to 42 (average 22.5) months after diagnosis of cancer in a brother or sister. Matched controls were obtained from respondents to the Child Health Supplement of the National Health Interview Survey administered in 1988 (CHS88). Before diagnosis, the prevalence of parent-reported emotional/behavioral problems among siblings was similar to that in the general population (7.7% vs 6.3%; p = not significant). After diagnosis, prevalence rose to 18% among siblings. When siblings were grouped according to the presence or absence of problems exacerbated by and/or arising after diagnosis, four levels of adaptation, consistent with scores on the Behavior Problem Scales from the CHS88, emerged. This differentiation may help explain inconsistencies in sibling response reported previously and provides a framework for investigating factors that enhance adaptation.

Adaptation, Psychological↗

[Familiarity, favorability, and cognitive complexity: integration of frequency of interaction hypothesis and vigilance hypothesis].

Previous studies using Bieri's 'cognitive complexity' score had supported 'vigilance hypothesis' which assumed that impressions of unfavorable persons were more complex than favorable persons. Thus, Bieri's measure seemed to be invalid because the findings were completely contrary to 'frequency of interaction hypothesis', presented in the theoretical framework of 'cognitive complexity', which assumed that impressions of familiar persons were more complex than unfamiliar persons, since people could be supposed to have more intimate acquaintance with favorable persons. The purpose of present study was to indicate the invalidity was caused by the research design where familiarity was dependent on favorability and to show that even Bieri's score could support 'interaction hypothesis', if one variables could be statistically orthogonized to the other. In each of two surveys reported, about two hundred female undergraduates completed a Rep test where they rated favorable and unfavorable persons on the basis of some dimensions which included favorability and familiarity. The results obtained through various regression analyses supported the above predictions. Moreover, it was revealed that, with favorability controlled, Bieri's score showed almost linear increases as familiarity increased, though the score of extremely unfamiliar persons was rather higher than the score the linear function could predict.

Adult↗

Setting handicap goals with elderly people: a pilot study of the Life Strengths Interview.

OBJECTIVE: To assess whether the Life Strengths Interview (LSI) is a useful clinical framework to identify handicap goals. DESIGN: Clinical case studies. SETTINGS: Two elderly care rehabilitation hospitals. SUBJECTS: Five people, whose ages ranged from 73 to 90 years. All participants were aware of their likely resultant disability, scored 25+ out of a possible 30 with the Mini-Mental State Examination, were able to communicate effectively and were due to be discharged home in approximately one month. INTERVENTIONS: Each participant undertook the LSI process with the research occupational therapist. MAIN OUTCOME MEASURES: Identified rehabilitation goals and their achievement. RESULTS: Goals were focused around families and other support networks. Six to eight weeks following discharge, achievement of goals varied. CONCLUSIONS: This pilot study suggests that the LSI may be a useful clinical framework but further research needs to investigate whether a modified clinical version may be more suitable.

Activities of Daily Living↗

Comparison of the combined monitoring-based and modelling-based priority setting scheme with partial order theory and random linear extensions for ranking of chemical substances.

The combined monitoring-based and modelling-based priority setting scheme (COMMPS) used to establish a priority setting list within the EU Water Framework Directive plays a major role in the European environmental policy on chemical substances. The COMMPS procedure can be classified as a so-called scoring method. The applied functional relationship and weight factors are established based on expert judgement, which unfortunately appears to be vulnerable to subjective inputs. In this study an alternative priority setting methods based on partial order theory (POT) and random linear extensions (RLE) is suggested and compared to the COMMPS procedure. The POT/RLE is characterised as being based on fewer assumptions concerning functional relationships and does not apply weighting factors. Using the POT/RLE methodology a different ranking result occur than when using the COMMPS procedure. Eight of the top 20 substances from the COMMPS procedure are not ranked within the top 20 when using POT/RLE. From the viewpoint of environmental protection, especially the substances that have been given low priority in the COMMPS procedure, but a high rank in POT/RLE, are of interest in a regulatory context. These substances are naphthalene, trichloromethane, isoproturon, metolachlor, endosulfan, acenaphthene, alachlor and dichloromethane. An analysis of the ability of the descriptors to separate the single substance discloses that the most significant descriptor is the concentrations detected in the environment. Further, the frequency of detection is not applied as a descriptor in the COMMPS procedure. However, if this descriptor was to be applied the analysis revealed that it would have been the third most significant descriptor.

Algorithms↗

Development and clinical implementation of an enhanced display algorithm for use in networked electronic portal imaging.

PURPOSE: To introduce and clinically validate a preprocessing algorithm that allows clinical images from an electronic portal imaging device (EPID) to be displayed on any computer monitor, without loss of clinical usability. The introduction of such a system frees EPI systems from the constraints of fixed viewing workstations and increases mobility of the images in a department. METHODS AND MATERIALS: The preprocessing algorithm, together with its variable parameters is introduced. Clinically, the algorithm is tested using an observer study of 316 EPID images of the pelvic region in the framework of treatment of carcinoma of the cervix and endometrium. Both anterior-posterior (AP/PA) and latero-lateral (LAT) images were used. The images scored were taken from six different patients, five of whom were obese, female, and postmenopausal. The result is tentatively compared with results from other groups. The scoring system, based on the number of visible landmarks in the port, is proposed and validated. Validation was performed by having the observer panel score images with artificially induced noise levels. A comparative study was undertaken with a standard automatic window and leveling display technique. Finally, some case studies using different image sites and EPI detectors are presented. RESULTS: The image quality for all images in this study was deemed to be clinically useful (mean score >1). Most of the images received a score which was second highest (AP/PA landmarks > or =6 and LAT landmarks > or =5). Obesity, which has been an important factor determining the image quality, was not seen to be a factor here. Compared to standard techniques a highly significant improvement was determined with regard to clinical usefulness. The algorithm performs fast (less than 9 seconds) and needs no additional user interaction in most of the cases. The algorithm works well on both direct detection portal imagers and camera-based imagers whether analog or digital cameras. CONCLUSIONS: We have demonstrated that it is possible to preprocess EPIs in such a way that the clinically relevant landmarks are easily detected on a generic computer screen. The algorithm is system-independent and fast. This allows for the encoding of EPIs in more generalized commercial formats so that distribution of images is facilitated.

Algorithms↗

Rehabilitation following hip fracture surgery: a comparative study of females and males.

PURPOSE: To compare patient, fracture and rehabilitation variables between male and female patients during the rehabilitation period immediately following surgical repair of hip fracture (HF). METHODS: A prospective cohort study was conducted in a rehabilitation geriatric ward in a tertiary university hospital in southern Israel. The study group consisted of 808 elderly patients, 65 years of age or older, selected for hospitalized rehabilitation following surgery for HF. The measurements included functional studies by the Functional Independence Measure (FIM) scale, mental status by Folstein Minimental Test and Clock Drawing Test, Geriatric Depression Screening Scale (GDS), demographic and social parameters, laboratory tests, length of rehabilitation, complications and mortality during rehabilitation. RESULTS: Six hundred and fourteen patients (76%) were women and 194 (24%) were men. The mean age ( +/- SD) of the women was 78.4 +/- 7.1 years and of the men was 77.8 +/- 7.5 (NS). There were no significant differences between women and men in terms of the anatomic site of the fracture or the type of surgery, the complication rate or mortality during rehabilitation, the length of time needed for rehabilitation, the framework to which the patient was discharged, FIM values before the HF, on admission and at the end of rehabilitation, or the difference between FIM scores at these last two points in time. CONCLUSIONS: In selected elderly patients with HF gender does not affect variables associated with hip fracture, the rehabilitation process immediately following the fracture, or the results of rehabilitation.

Aged↗

MO-GCAN: multi-omics integration based on graph convolutional and attention networks.

MOTIVATION: Cancer subtypes play a critical role in disease progression, prognosis, and treatment, making their detection essential for tailoring precision medicine. Studies have shown that multi-omics integration outperforms single-omics approaches in cancer subtyping tasks. However, due to the high-dimensionality of multi-omics data, many existing studies either fail to capture the correlation between true labels and learned features, or lack sufficient capacity to model complex biological representations. These limitations hinder the full potential of leveraging the rich and complementary information embedded in multi-omics datasets. RESULT: We propose a framework that leverages supervised feature learning and classification based on a graph-based learning approach with attention mechanism for cancer subtyping. More specifically, we train graph convolutional network models on each omics dataset to extract latent representations, which are then concatenated to form a comprehensive multi-omics feature embedding. We further develop sample fusion network based on the omics-specific graphs, incorporating the derived features and feeding them into a graph attention model for subtype classification. This two-stage multi-omics framework is applied to eight cancer types, with performance evaluated in terms of test accuracy, training time, macro-averaged precision, recall, and F-score. Experimental results show that the proposed method outperforms state-of-the-art approaches across various cancer types. Additionally, we provide empirical evidence supporting the hypothesis that retaining a limited number of high-confidence edges and utilizing enriched embeddings from intermediate graph neural network layers can improve predictive performance. AVAILABILITY AND IMPLEMENTATION: Data and the code are available at https://github.com/YD-00/MO-GCAN-Updated.git.

Neoplasms↗

United Kingdom back pain exercise and manipulation (UK BEAM) randomised trial: effectiveness of physical treatments for back pain in primary care.

OBJECTIVE: To estimate the effect of adding exercise classes, spinal manipulation delivered in NHS or private premises, or manipulation followed by exercise to "best care" in general practice for patients consulting with back pain. [See figure]. DESIGN: Pragmatic randomised trial with factorial design. SETTING: 181 general practices in Medical Research Council General Practice Research Framework; 63 community settings around 14 centres across the United Kingdom. PARTICIPANTS: 1334 patients consulting their general practices about low back pain. MAIN OUTCOME MEASURES: Scores on the Roland Morris disability questionnaire at three and 12 months, adjusted for centre and baseline scores. RESULTS: All groups improved over time. Exercise improved mean disability questionnaire scores at three months by 1.4 (95% confidence interval 0.6 to 2.1) more than "best care." For manipulation the additional improvement was 1.6 (0.8 to 2.3) at three months and 1.0 (0.2 to 1.8) at 12 months. For manipulation followed by exercise the additional improvement was 1.9 (1.2 to 2.6) at three months and 1.3 (0.5 to 2.1) at 12 months. No significant differences in outcome occurred between manipulation in NHS premises and in private premises. No serious adverse events occurred. CONCLUSIONS: Relative to "best care" in general practice, manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months; and exercise achieved a small benefit at three months but not 12 months.

Adult↗

Analysis of an optimal hidden Markov model for secondary structure prediction.

BACKGROUND: Secondary structure prediction is a useful first step toward 3D structure prediction. A number of successful secondary structure prediction methods use neural networks, but unfortunately, neural networks are not intuitively interpretable. On the contrary, hidden Markov models are graphical interpretable models. Moreover, they have been successfully used in many bioinformatic applications. Because they offer a strong statistical background and allow model interpretation, we propose a method based on hidden Markov models. RESULTS: Our HMM is designed without prior knowledge. It is chosen within a collection of models of increasing size, using statistical and accuracy criteria. The resulting model has 36 hidden states: 15 that model alpha-helices, 12 that model coil and 9 that model beta-strands. Connections between hidden states and state emission probabilities reflect the organization of protein structures into secondary structure segments. We start by analyzing the model features and see how it offers a new vision of local structures. We then use it for secondary structure prediction. Our model appears to be very efficient on single sequences, with a Q3 score of 68.8%, more than one point above PSIPRED prediction on single sequences. A straightforward extension of the method allows the use of multiple sequence alignments, rising the Q3 score to 75.5%. CONCLUSION: The hidden Markov model presented here achieves valuable prediction results using only a limited number of parameters. It provides an interpretable framework for protein secondary structure architecture. Furthermore, it can be used as a tool for generating protein sequences with a given secondary structure content.

Computational Biology↗

An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.

An important but largely unmet challenge in understanding the mechanisms that govern the formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic, and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from 12 genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasets--based on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genes--provisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true-positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.

Animals↗