Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics

Purpose: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was 1,407 ( 897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

Dissemination of periodic mammography and patterns of use, by birth cohort, in Catalonia (Spain)

Background: In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006. Methods: Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year. Results: For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938–1942 to 37.3 years of age for women born in 1963–1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50–69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50–69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40–49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones. Conclusion: Mammography in Catalonia became more widely implemented during the 1990s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia.

Time patterns and perceptions of online learning success factors

Online learning provides the opportunity to work on academic tasks at any time at the same time as doing other activities, such as using in web 2.0 tools. This study identifies factors that contribute to success in online learning from the students¿ perspective and their relationship with time patterns. A survey of learning outputs was used to find relationships between students¿ satisfaction, knowledge acquisition and knowledge transfer with time for working on academic tasks. In this study, 199 students from a university in Mexico completed the survey. Findings suggest that knowledge transfer has a significant association with the number of hours online per day, hours spent on social networks and the use made of e-learning during working hours. Learner satisfaction has a strong relationship with the time in years a learner has been using the Internet and the number of hours devoted to the course per week. The findings of this research will be helpful for faculty and instructional designers for implementing learning strategies.

Diet-related buccal dental microwear patterns in central african pygmy foragers and bantu-speaking farmer and pastoralist populations.

Pygmy hunter-gatherers from Central Africa have shared a network of socioeconomic interactions with non-Pygmy Bantu speakers since agropastoral lifestyle spread across sub-Saharan Africa. Ethnographic studies have reported that their diets differ in consumption of both animal proteins and starch grains. Hunted meat and gathered plant foods, especially underground storage organs (USOs), are dietary staples for pygmies. However, scarce information exists about forager-farmer interaction and the agricultural products used by pygmies. Since the effects of dietary preferences on teeth in modern and past pygmies remain unknown, we explored dietary history through quantitative analysis of buccal microwear on cheek teeth in well-documented Baka pygmies. We then determined if microwear patterns differ among other Pygmy groups (Aka, Mbuti, and Babongo) and between Bantu-speaking farmer and pastoralist populations from past centuries. The buccal dental microwear patterns of Pygmy hunter-gatherers and non-Pygmy Bantu pastoralists show lower scratch densities, indicative of diets more intensively based on nonabrasive foodstuffs, compared with Bantu farmers, who consume larger amounts of grit from stoneground foods. The Baka pygmies showed microwear patterns similar to those of ancient Aka and Mbuti, suggesting that the mechanical properties of their preferred diets have not significantly changed through time. In contrast, Babongo pygmies showed scratch densities and lengths similar to those of the farmers, consistent with sociocultural contacts and genetic factors. Our findings support that buccal microwear patterns predict dietary habits independent of ecological conditions and reflect the abrasive properties of preferred or fallback foods such as USOs, which may have contributed to the dietary specializations of ancient human populations.

Common Quail (Coturnix coturnix) post-breeding movements and migration patterns: from knowledge to management.

Hemos investigado los patrones de los movimientos postcría de la codorniz común (Coturnix coturnix) en la península ibérica con el fin de describir su fenología de paso migratorio y algunas características fisiológicas de los individuos. Esta información es necesaria para un ajuste óptimo de los períodos de caza. Hemos trabajado a partir de dos conjuntos de datos: a) capturas efectuadas en una zona que no es de cría (Garraf) de agosto a octubre en 2009 y 2010; b) recuperaciones, posteriores a la presunta época de cría, de individuos anillados en Europa y recapturados en España durante el período 1933-2005. Los resultados obtenidos muestran que los movimientos postcría en Garraf están formados por dos oleadas: una primera, que se produce sobre el 10 VIII, formada principalmente por jóvenes del año inactivos sexualmente que no son fisiológicamente migrantes; y una segunda, mucho más intensa, que se produce sobre el 17 IX, formada principalmente por migrantes jóvenes del año inactivos sexualmente. La época de caza en España tiene lugar principalmente durante la primera oleada, preservando el paso de los migrantes provenientes de España y de otros países europeos. La información de los movimientos postcría en otras regiones españolas y en otros países europeos en los que la codorniz común es una especie cinegética popular, permitiría mejorar el ajuste entre el período de caza y la migración, proporcionando recomendaciones de gestión cinegética más precisas para esta especie.

Gene flow and gene flux shape evolutionary patterns of variation in Drosophila subobscura

Gene flow (defined as allele exchange between populations) and gene flux (defined as allele exchange during meiosis in heterokaryotypic females) are important factors decreasing genetic differentiation between populations and inversions. Many chromosomal inversions are under strong selection and their role in recombination reduction enhances the maintenance of their genetic distinctness. Here we analyze levels and patterns of nucleotide diversity, selection and demographic history, using 37 individuals of Drosophila subobscura from Mount Parnes (Greece) and Barcelona (Spain). Our sampling focused on two frequent O-chromosome arrangements that differ by two overlapping inversions (OST and O3+4), which are differentially adapted to the environment as observed by their opposing latitudinal clines in inversion frequencies. The six analyzed genes (Pif1A, Abi, Sqd, Yrt, Atpa and Fmr1) were selected for their location across the O-chromosome and their implication in thermal adaptation. Despite the extensive gene flux detected outside the inverted region, significant genetic differentiation between both arrangements was found inside it. However, high levels of gene flow were detected for all six genes when comparing the same arrangement among populations. These results suggest that the adaptive value of inversions is maintained, regardless of the lack of genetic differentiation within arrangements from different populations, and thus favors the Local Adaptation hypothesis over the Coadapted Genome hypothesis as the basis of the selection acting on inversions in these populations.

Patterns of nucleotide diversity at the regions encompassing the Drosophila insulin-like peptide (dilp) genes: demography vs positive selection in Drosophila melanogaster.

In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events.

Dynamic Criteria: a Longitudinal Analysis of Professional Basketball Players" Outcomes

This paper describes the fluctuations of temporal criteria dynamics in the context of professional sport. Specifically, we try to verify the underlying deterministic patterns in the outcomes of professional basketball players. We use a longitudinal approach based on the analysis of the outcomes of 94 basketball players over ten years, covering practically players" entire career development. Time series were analyzed with techniques derived from nonlinear dynamical systems theory. These techniques analyze the underlying patterns in outcomes without previous shape assumptions (linear or nonlinear). These techniques are capable of detecting an intermediate situation between randomness and determinism, called chaos. So they are very useful for the study of dynamic criteria in organizations. We have found most players (88.30%) have a deterministic pattern in their outcomes, and most cases are chaotic (81.92%). Players with chaotic patterns have higher outcomes than players with linear patterns. Moreover, players with power forward and center positions achieve better results than other players. The high number of chaotic patterns found suggests caution when appraising individual outcomes, when coaches try to find the appropriate combination of players to design a competitive team, and other personnel decisions. Management efforts must be made to assume this uncertainty.

Activity patterns and foraging behaviour of Audouin's gulls at the Ebro Delta, NW Mediterranean.

Twenty Audouin´s gulls, Larus audouinii, breeding in the Ebro Delta (NW Mediterranean) were radio-tracked in 1998 to study their foraging behaviour and activity patterns. Some detrimental effects of tagging on the breeding success of the birds were detected, especially when both members of the pair were tagged. The results were actually constrained by the low number of locations due to natural breeding failure and failure in tag emission, as well as the adverse effect of tagging. However, through a combination of aircraft surveys at sea and a fixed station for automatic tracking of the presence of the birds at the colony, novel individual-based information of home ranges and activity patterns was obtained. Trawler fishing activity seemed to influence both the foraging range and habitat use: while trawlers operated, gulls overlapped their fishing grounds with vessels, probably to scavenge on discards. Very few locations were obtained during a trawling moratorium period, although they were all recorded in coastal bays and terrestrial habitats. During the trawling activity period, gulls ranged over a minimum convex polygon area of 2900 km2. Gulls were tracked up to 40 km from the colony, but some individuals were observed beyond 150 km while still breeding. Arrivals and departures from the colony were in accordance with the trawling timetable. However, most birds also showed some nocturnal foraging activity, probably linked to active fishing of clupeoids (following diel migrations) or to the exploitation of purse-seine fishing activity. Foraging trips lasted on average 15 hours: males performed significantly shorter trips than females, which spent more time outside the colony. The proportion of nocturnal time involved in the foraging trips was the same for males and females, but whilst all males initiated their trips both during the day and at night, some females only initiated their trips during the day. Hatching success was found to be related to foraging effort by males. Gulls spent on average ca. 38% of their time budget outside the nesting territory, representing the time devoted mainly to flying, foraging and other activities.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

The odd couple: contrasting phylogeographic patterns in two sympatric sibling species of woodlouse-­‐hunter spiders in the Canary Islands

Comparative phylogeography seeks for commonalities in the spatial demographic history of sympatric organisms to characterize the mechanisms that shaped such patterns. The unveiling of incongruent phylogeographic patterns in co-occurring species, on the other hand, may hint to overlooked differences in their life histories or microhabitat preferences. The woodlouse-hunter spiders of the genus Dysdera have undergone a major diversi cation on the Canary Islands. The species pair Dysdera alegranzaensis and Dysdera nesiotes are endemic to the island of Lanzarote and nearby islets, where they co-occur at most of their known localities. The two species stand in sharp contrast to other sympatric endemic Dysdera in showing no evidence of somatic (non-genitalic) differentiation. Phylogenetic and population genetic analyses of mitochondrial cox1 sequences from an exhaustive sample of D. alegranzaensis and D. nesiotes specimens, and additional mitochondrial (16S, L1, nad1) and nuclear genes (28S, H3) were analysed to reveal their phylogeographic patterns and clarify their phylogenetic relationships. Relaxed molecular clock models using ve calibration points were further used to estimate divergence times between species and populations. Striking differences in phylogeography and population structure between the two species were observed. Dysdera nesiotes displayed a metapopulation-like structure, while D. alegranzaensis was characterized by a weaker geographical structure but greater genetic divergences among its main haplotype lineages, suggesting more complex population dynamics. Our study con rms that co-distributed sibling species may exhibit contrasting phylogeographic patterns in the absence of somatic differentiation. Further ecological studies, however, will be necessary to clarify whether the contrasting phylogeographies may hint at an overlooked niche partitioning between the two species. In addition, further comparisons with available phylogeographic data of other eastern Canarian Dysdera endemics con rm the key role of lava ows in structuring local populations in oceanic islands and identify localities that acted as refugia during volcanic eruptions

Patterns of primary growth increments in otoliths of Sparus aurata larvae in relation to water temperature and food consumption

Sparus aurata larvae reared under controlled water-temperature conditions during the first 24 days after hatching displayed a linear relationship between age (t) and standard length (SL): SL = 2.68 + 0.19 t (r2 = 0.91l). Increments were laid down in the sagittae with daily periodicity starting on day of hatching. Standard length (SL) and sagittae radius (OR) were correlated: SL(mm) = 2.65 + 0.012 OR(mm). The series of measurements of daily growth increment widths (DWI), food density and water temperature were analyzed by means of time series analysis. The DWI series were strongly autocorrelated, the growth on any one day was dependent upon growth on the previous day. Time series of water temperatures showed, as expected, a random pattern of variation, while food consumed daily was a function of food consumed the two previous days. The DWI series and the food density were correlated positively at lags 1 and 2. The results provided evidence of the importance of food intake upon the sagittae growth when temperature is optimal (20ºC). Sagittae growth was correlated with growth on the previous day, so this should be taken into account when fish growth is derived from sagittae growth rates.

Lower incisor dentoalveolar compensation and symphysis dimensions among Class I and III malocclusion patients with different facial vertical skeletal patterns

Objective: To compare lower incisor dentoalveolar compensation and mandible symphysis morphology among Class I and Class III malocclusion patients with different facial vertical skeletal patterns. Materials and Methods: Lower incisor extrusion and inclination, as well as buccal (LA) and lingual (LP) cortex depth, and mandibular symphysis height (LH) were measured in 107 lateral cephalometric x-rays of adult patients without prior orthodontic treatment. In addition, malocclusion type (Class I or III) and facial vertical skeletal pattern were considered. Through a principal component analysis (PCA) related variables were reduced. Simple regression equation and multivariate analyses of variance were also used. Results: Incisor mandibular plane angle (P < .001) and extrusion (P  =  .03) values showed significant differences between the sagittal malocclusion groups. Variations in the mandibular plane have a negative correlation with LA (Class I P  =  .03 and Class III P  =  .01) and a positive correlation with LH (Class I P  =  .01 and Class III P  =  .02) in both groups. Within the Class III group, there was a negative correlation between the mandibular plane and LP (P  =  .02). PCA showed that the tendency toward a long face causes the symphysis to elongate and narrow. In Class III, alveolar narrowing is also found in normal faces. Conclusions: Vertical facial pattern is a significant factor in mandibular symphysis alveolar morphology and lower incisor positioning, both for Class I and Class III patients. Short-faced Class III patients have a widened alveolar bone. However, for long-faced and normal-faced Class III, natural compensation elongates the symphysis and influences lower incisor position.