Adjusting ROC curve for Covariates with AROC R package

The ability of a medical test to differentiate between diseased and non-diseased states is of vital importance and must be screened by statistical analysis for reliability and improvement. The receiver operating characteristic (ROC) curve remains a popular method of marker analysis, disease screening and diagnosis. Covariates in this field related to the subject’s characteristics are incorporated in the analysis to avoid bias. The covariate adjusted ROC (AROC) curve was proposed as a method of incorporation. The AROC R-package was recently released and brings various methods of estimation based on multiple authors work. The aim of this study was to explore the AROC package functionality and usability using real data noting its possible limitations. The main methods of the package were capable of incorporating different and multiple variables, both categorical and continuous, in the AROC curve estimation. When tested for the same data, AROC curves are generated with no statistical differences, regardless of method. The package offers a variety of methods to estimate the AROC curve complemented with predictive checks and pooled ROC estimation. The package offers a way to conduct a more thorough ROC and AROC analysis, making it available for any R user.This work has been supported by FCT - Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/202

Costs and consequences of chronic pain due to musculoskeletal disorders from a health system perspective in Chile

Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. Background: Chronic pain is a prevalent and distressing condition caused by an unceasing pain lasting more than 3 months or a pain that persists beyond the normal healing time. There is evidence of inadequate management partly explained by the unawareness regarding the magnitude of the problem. Objectives: To estimate the annual expected costs and consequences of chronic pain caused by musculoskeletal diseases from the health system perspective in Chile. Methods: A Markov cohort model was built to represent chronic pain and estimate expected costs and consequences over 1-year time horizon. Transition probabilities were obtained through expert elicitation. Consequences examined were: years lost to disability (YLD), depression, anxiety, and productivity losses. Direct health care costs were estimated using local sources. Probabilistic sensitivity analysis was performed to characterize second-order uncertainty. Results: The annual expected cost due to musculoskeletal chronic pain was estimated in USD $1387.2 million, equivalent to 0.417$94 million (Bayesian credibility interval 95% $49.1-$156.26). Productivity losses were also important cost, although early retirement and presenteeism were not measured. Chronic pain causes 137,037 YLDs. Conclusion: Chronic pain is not only an important cause of disability but also responsible for high social and financial burden in Chile. Public health programs focused on managing chronic pain may decrease burden of disease and possibly reduce costs.

Efecto del estrés hídrico a distintas temperaturas sobre la germinación de semillas de Bulnesia retama (Gill. ex. Hook.) Griseb. -Zigofiláceas - en San Luis, Argentina

Se estudió la germinación de semillas de Bulnesia retama frente a condiciones de estrés hídrico, simulado con PEG6000 a distintas temperaturas, y su recuperación ante el estrés. Las semillas recolectadas en San Luis (Argentina) se colocaron a germinar en bolsas de polietileno, con soluciones de PEG6000, para simular potenciales agua: 0 (Control con agua destilada); -0,25; -0,5; -0,75; -1; -1,25 y -1,5 MPa en estufa de cultivo y en oscuridad a temperaturas de 18º, 25º y 32 ºC. Las semillas que no germinaron ante el estrés simulado fueron lavadas y colocadas a germinar nuevamente en agua destilada a 25 ºC. Se registró el porcentaje y la velocidad de germinación de las semillas. Las semillas colocadas en agua destilada germinaron con porcentajes superiores al 70% en el rango de 18º a 32 ºC sin diferencias entre temperaturas. A 18 ºC, el porcentaje y la velocidad de germinación disminuyeron significativamente en todos los tratamientos con PEG, mientras que a 25 ºC la respuesta germinativa fue afectada a partir de -1 MPa. A 32 ºC la germinación no difirió del control en las primeras 48 horas hasta potenciales osmóticos de -1 MPa, pero luego la velocidad y porcentaje de germinación disminuyeron significativamente. El porcentaje de germinación en la recuperación después del estrés fue similar al porcentaje del control original, lo que demuestra que las semillas no germinan si no tienen determinadas condiciones hídricas y térmicas. Estos resultados pueden ser el resultado de la adaptación de la especie a las condiciones ambientales propias de la región.Se estudió la germinación de semillas de Bulnesia retama frente a condiciones de estrés hídrico, simulado con PEG6000 a distintas temperaturas, y su recuperación ante el estrés. Las semillas recolectadas en San Luis (Argentina) se colocaron a germinar en bolsas de polietileno, con soluciones de PEG6000, para simular potenciales agua: 0 (Control con agua destilada); -0,25; -0,5; -0,75; -1; -1,25 y -1,5 MPa en estufa de cultivo y en oscuridad a temperaturas de 18º, 25º y 32 ºC. Las semillas que no germinaron ante el estrés simulado fueron lavadas y colocadas a germinar nuevamente en agua destilada a 25 ºC. Se registró el porcentaje y la velocidad de germinación de las semillas. Las semillas colocadas en agua destilada germinaron con porcentajes superiores al 70% en el rango de 18º a 32 ºC sin diferencias entre temperaturas. A 18 ºC, el porcentaje y la velocidad de germinación disminuyeron significativamente en todos los tratamientos con PEG, mientras que a 25 ºC la respuesta germinativa fue afectada a partir de -1 MPa. A 32 ºC la germinación no difirió del control en las primeras 48 horas hasta potenciales osmóticos de -1 MPa, pero luego la velocidad y porcentaje de germinación disminuyeron significativamente. El porcentaje de germinación en la recuperación después del estrés fue similar al porcentaje del control original, lo que demuestra que las semillas no germinan si no tienen determinadas condiciones hídricas y térmicas. Estos resultados pueden ser el resultado de la adaptación de la especie a las condiciones ambientales propias de la región

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts

Osteoblast and adipocyte are derived from common mesenchymal progenitor cells. The bone loss of osteoporosis is associated with altered progenitor differentiation from an osteoblastic to an adipocytic lineage. In this study, a comparative analysis of gene expression profiling using cDNA microarray and realtime-PCR indicated that Zinc finger protein 467 (Zfp467) involved in adipocyte and osteoblast differentiation of cultured adipose derived stem cells (ADSCs). Our results showed that RNA interference for Zfp467 in ADSCs inhibited adipocyte formation and stimulated osteoblast commitment. The mRNA levels of osteogenic and adipogenic markers in ADSCs were regulated by si-Zfp467. Zfp467 RNAi in ADSCs could restore bone function and structure in an ovariectomized (OVX)-induced osteoporotic mouse model. Thus Zfp467 play an important role in ADSCs differentiation to adipocyte and osteoblast. This has relevance to therapeutic interventions in osteoporosis, including si-Zfp467-based therapies currently available, and may be of relevance for the use of adipose-derived stem cells for tissue engineering

Estudio preliminar de la ingesta de nutrientes de niños deportistas de Sierra Nevada

A study was conducted of the diet of a child Alpine ski competition team (Monachil Club, Sierra Nevada). The children,aged between 7-12 years old, were divided into two groups. One of which were residents at a ski resort and the other,residents from different cities, who practised skiing at the same resort at weekends only.A 24-hour recall questionnaire was carried out, from which the following data was collected: The mean energy valuefrom diet intake was determined at 3,218 ± 819 Kcal/day (ski resort group) and 2,485 ± 600 Kcal/day (city group). Nosignificant differences between the groups was observed (p≥0.3). The distribution of energy from energetic nutrients wascorrect for the ski resort group, both at the weekend and during the week; the city group had an excessive intake oflipids (43%) and proteins (17%), and the energy from carbohydrates did not reach 55%. A modification in the diet andintake of energy and nutrients was observed when the children moved from their family home to the ski resortSe ha realizado un estudio de la dieta del equipo de competición infantil en esquí alpino (Club Monachil, SierraNevada). Son niños con edades entre 7-12 años. Se consideran dos grupos, los residentes en la estación de esquí ylos de ciudad que esquían en fin de semana.Se han realizado encuestas de recuerdo 24 horas. El valor medio de energía, es 3218 Kcal/dia ± 819 (grupo de lasierra) y 2485 Kcal/dia ± 600 (grupo de ciudad), no existen diferencias significativas entre grupos (p≥0,3). Ladistribución de energía a partir de los nutrientes energéticos es correcta para los niños deportistas de la sierra, tantoen el fin de semana como entre semana; los niños deportistas de ciudad tienen un consumo excesivo de lípidos (43%)y prótidos (17%), el aporte de energía de carbohidratos no llega al 55%. Se observa una modificación de la dietay del consumo de energía y nutrientes cuando los niños pasan del hogar familiar a la practica del deporte

Comparative cytogenetic analysis of two grasshopper species of the tribe Abracrini (Ommatolampinae, Acrididae)

The grasshopper species Orthoscapheus rufipes and Eujivarus fusiformis were analyzed using several cytogenetic techniques. The karyotype of O. rufipes, described here for the first time, had a diploid number of 2n = 23, whereas E. fusiformis had a karyotype with 2n = 21. The two species showed the same mechanism of sex determination (XO type) but differed in chromosome morphology. Pericentromeric blocks of constitutive heterochromatin (CH) were detected in the chromosome complement of both species. CMA3/DA/DAPI staining revealed CMA3-positive blocks in CH regions in four autosomal bivalents of O. rufipes and in two of E. fusiformis. The location of active NORs differed between the two species, occurring in bivalents M6 and S9 of O. rufipes and M6 and M7 of E. fusiformsi. The rDNA sites revealed by FISH coincided with the number and position of the active NORs detected by AgNO3 staining. The variability in chromosomal markers accounted for the karyotype differentiation observed in the tribe Abracrini

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats

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