A new parsimonious model for ordinal longitudinal data with application to subjective evaluations of a gastrointestinal disease

In this paper, a new discrete statistical model for ordered categorical data is proposed via fixed-point discretization of a beta latent variable. The resulting discretized beta distribution has a highly flexible shape and it can be either over-dispersed or under-dispersed with respect to the binomial distribution. It has only two parameters, which may therefore parsimoniously depend on covariates and on random effects, providing new tools for the analysis of structured, clustered or longitudinal ordinal data. Practical examples and advices are given and an application of the new model to subjective evaluations of a gastrointestinal disease is shown

Decision-making in drug development using a composite definition of success

Evidence-based quantitative methodologies have been proposed to inform decision-making in drug development, such as metrics to make go/no-go decisions or predictions of success, identified with statistical significance of future clinical trials. While these methodologies appropriately address some critical questions on the potential of a drug, they either consider the past evidence without predicting the outcome of the future trials or focus only on efficacy, failing to account for the multifaceted aspects of a successful drug development. As quantitative benefit-risk assessments could enhance decision-making, we propose a more comprehensive approach using a composite definition of success based not only on the statistical significance of the treatment effect on the primary endpoint but also on its clinical relevance and on a favorable benefit-risk balance in the next pivotal studies. For one drug, we can thus study several development strategies before starting the pivotal trials by comparing their predictive probability of success. The predictions are based on the available evidence from the previous trials, to which new hypotheses on the future development could be added. The resulting predictive probability of composite success provides a useful summary to support the discussions of the decision-makers. We present a fictive, but realistic, example in major depressive disorder inspired by a real decision-making case

Spatial distribution of surface EMG on trapezius and lumbar muscles of violin and cello players in single note playing

Musicians activate their muscles in different patterns, depending on their posture, the instrument being played, and their experience level. Bipolar surface electrodes have been used in the past to monitor such activity, but this method is highly sensitive to the location of the electrode pair. In this work, the spatial distribution of surface EMG (sEMG) of the right trapezius and right and left erector spinae muscles were studied in 16 violin players and 11 cello players. Musicians played their instrument one string at a time in sitting position with/without backrest support. A 64 sEMG electrode (16x4) grid, 10mm inter-electrode distance (IED), was placed over the middle and lower trapezius (MT and LT) of the bowing arm. Two 16x2 electrode grids (IED=10mm) were placed on the left and right erector spinae muscles. Subjects played each of the four strings of the instrument either in large (1bow/s) or detaché tip/tail (8bows/s) bowing in two sessions (two days). In each of two days, measurements were repeated after half an hour of exercise to see the effect of exercise on the muscle activity and signal stability. A “muscle activity index” (MAI) was defined as the spatial average of the segmented active region of the RMS map. Spatial maps were automatically segmented using the watershed algorithm and thresholding. Results showed that, for violin players, sliding the bow upward from the tip toward the tail results in a higher MAI for the trapezius muscle than a downward bow. On the contrary, in cello players, higher MAI is produced in the tail to tip movement. For both instruments, an increasing MAI in the trapezius was observed as the string position became increasingly lateral, from string 1 (most medial) toward string 4 (most lateral). Half an hour of performance did not cause significant differences between the signal quality and the MAI values measured before and after the exercise. The MAI of the left and right erector spinae was smaller in the case of backrest support, especially for violin players. Back muscles of violin and cello players were activated asymmetrically, specifically in fast movements (detaché tip/tail). These findings demonstrate the sensitivity and stability of the technique and justify more extensive investigation following this proof of concept

Cine argentino: políticas de programación para su televisación

El presente trabajo exhibirá la evolución de la presencia en pantalla de films argentinos, en la oferta de programación de las señales televisivas argentinas 9, 11 y 13 durante el periodo 1989-1992. La investigación presentará las continuidades y rupturas de la importancia otorgada por los diferentes canales al cine nacional durante el periodo analizado. Para ello se problematizará sobre la presencia de las películas argentinas en relación con las producidas en otros países.Facultad de Periodismo y Comunicación Socia

Epidemiology of musculoskeletal injuries in a population of harness Standardbred racehorses in training

BACKGROUND: There is a substantial paucity of studies concerning musculoskeletal injuries in harness Standardbred racehorses. Specifically, little is known about the epidemiology of exercise-related musculoskeletal injuries. Most studies on this subject involve Thoroughbred racehorses, whose biomechanics and racing speed differ from Standardbred, making comparisons difficult. Here, a population of Standardbred racehorses trained at the same racecourse was studied over four years and a classification system for exercise-related musculoskeletal injuries was designed. The incidence rates of musculoskeletal injuries causing horses’ withdrawal from training for 15 days or longer were investigated. A mixed-effects Poisson regression model was used to estimate musculoskeletal injury rates and to describe significance of selected risk factors for exercise-related injuries in this population. RESULTS: A total of 356 trotter racehorses from 10 different stables contributed 8961 months at risk of musculoskeletal injuries. Four-hundred-and-twenty-nine injuries were reported and classified into 16 categories, based on their aetiology and anatomical localisation. The overall exercise-related injury rate was 4.79 per 100 horse months. When considering risk factors one by one in separate univariable analyses, we obtained the following results: rates did not differ significantly between genders and classes of age, whereas one driver seemed to cause fewer injuries than the others. Racing speed and racing intensity, as well as recent medical history, seemed to be significant risk factors (p < 0.001), while being shod or unshod during racing was not. On the other hand, when pooling several risk factors in a multivariable approach, only racing intensity turned out to be significant (p < 0.001), since racing speed and the racing intensity were partially confounded, being strongly correlated to one another. CONCLUSION: Characterizing epidemiology of exercise-related musculoskeletal injuries in trotter racehorses provides baseline incidence rate values. Incidence rates of stress fracture are lower in Standardbreds compared to Thoroughbreds, whereas the opposite is true for tendon and suspensory ligament injuries. In addition to identification of risk factors for musculoskeletal injuries among Standardbred racehorses, results suggest that racing intensity seems to be a protective predictor of risk and recent medical history could be used to identify horses at risk of injury

A proximity-based method to identify genomic regions correlated with a continuously varying environmental variable

Knowledge of markers in the human genome which show spatial patterns and display extreme correlation with different environmental determinants play an important role in understanding the factors which affect the biological evolution of our species. We used the genotype data of more than half a million single nucleotide polymorphisms (SNPs) from the data set Human Genome Diversity Panel (HGDP-CEPH -CEPH) and we calculated Spearman's correlation between absolute latitude and one of the two allele frequen- cies of each SNP. We selected SNPs with a correlation coefficient within the upper 1% tail of the distribution. We then used a criterion of proximity between significant variants to focus on DNA regions showing a continuous signal over a portion of the genome. Based on external information and genome annotations, we demonstrated that most regions with the strongest signals also have biological relevance. We believe this proximity requirement adds an edge to our novel method compared to the existing literature, highlighting several genes (for example DTNB, DOT1L, TPCN2, RELN, MSRA, NRG3) related to body size or shape, human height, hair color, and schizophrenia. Our approach can be applied generally to any measure of association between polymorphic frequencies and continuously varying environmental variable