Development of safety performance functions for Spanish two-lane rural highways on flat terrain

[EN] Over decades safety performance functions (SPF) have been developed as a tool for traffic safety in order to estimate the number of crashes in a specific road section. Despite the steady progression of methodological innovations in the crash analysis field, many fundamental issues have not been completely addressed. For instance: Is it better to use parsimonious or fully specified models? How should the goodness-of-fit of the models be assessed? Is it better to use a general model for the entire sample or specific models based on sample stratifications? This paper investigates the above issues by means of several SPFs developed using negative binomial regression models for two-lane rural highways in Spain. The models were based on crash data gathered over a 5-year period, using a broad number of explanatory variables related to exposure, geometry, design consistency and roadside features. Results show that the principle of parsimony could be too restrictive and that it provided simplistic models. Most previous studies apply conventional measurements (i.e., R-2, BIC, AIC, etc.) to assess the goodness-of-fit of models. Seldom do studies apply cumulative residual (CURE) analysis as a tool for model evaluation. This paper shows that CURE plots are essential tools for calibrating SPF, while also providing information for possible sample stratification. Previous authors suggest that sample segmentation increases the model accuracy. The results presented here confirm that finding, and show that the number of significant variables in the final models increases with sample stratification. This paper point out that fully models based on sample segmentation and on CURE may provide more useful insights about traffic crashes than general parsimonious models when developing SPF. (C) 2016 Elsevier Ltd. All rights reserved.The authors would like to thank the ERDF of the European Union for financial support via project "Bases para un sistema experto que permita la identificacion probabilistica de Tramos de Concentracion de Crashes (TCA)" under the "Programa Operativo FEDER de Andalucia 2007-2013". We also thank the Public Works Agency and the Regional Ministry of Public Works and Housing of the Regional Government of Andalusia. Griselda Lopez wishes to express her acknowledgement of the regional ministry of Economy, Innovation and Science of the regional government of Andalusia (Spain) for their scholarship to train teachers and researchers in Deficit Areas.Garach, L.; De Oña, J.; López-Maldonado, G.; Baena-Ruiz, L. (2016). Development of safety performance functions for Spanish two-lane rural highways on flat terrain. Accident Analysis & Prevention. 95:250-265. https://doi.org/10.1016/j.aap.2016.07.021S2502659

Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: a systematic review, meta-analysis, and meta-regression

Objective: This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS). Method: We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Co-primary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95 % confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030. Results: We evaluated 18 studies including, 1282 PCOS cases and 977 controls. Participants with PCOS were younger (MD = −2.38 years, 95 %CI -4.32 to -0.44), with higher BMI (MD = 1.16, 95 % CI 0.54–1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68–1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76–1.83), AMH (SMD = 0.97, 95 %CI 0.60–1,34), total testosterone (SMD = 2.48, 95 %CI 1.73–3.23), free testosterone (SMD = 1.37, 95 %CI 0.56–2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32–1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76–7.39), and lower sex hormone-binding globulin level (SMD = −1.34, 95 %CI −2.15 to −0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD = 0.76, 95 %CI 0.35–1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30–1.19), leptin (SMD = 2.82, 95 %CI 1.35–4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08–3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin. Conclusion: Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome

The effect of endometriosis on sexual function as assessed with the Female Sexual Function Index: systematic review and meta-analysis

Aim: To systematically compare sexual function between non-treated women with and without endometriosis. Methods: A systematic review was performed on PubMed/Medline, Scopus, EMBASE, Web of Science and Cochrane Library databases searching studies that analyzed sexual function (assessed with the 19-item Female Sexual Function Index [FSFI]), and dyspareunia, chronic pelvic pain and dysmenorrhea (assessed with a visual analogue scale [VAS]) in women with and with endometriosis. Results: In 4 studies, non-treated women with endometriosis presented a higher risk of female sexual dysfunction (mean total FSFI score = 26.55; OR = 2.38; 95% confidence interval [CI] = 1.12, 5.04). Although mean total FSFI scores were not significantly different between women with and without endometriosis (mean difference [MD] = -2.15; 95% CI -4.96, 0.67); all FSFI domain scores were significantly lower in women with endometriosis (n = 4 studies): desire (MD = -0.43; 95% CI -0.57, -0.19); arousal (MD = -0.66; 95% CI -1.15, -0.17); lubrication (MD = -0.41; 95% CI -0.79, -0.02); orgasm (MD = -0.40; 95% CI -0.73, -0.06); satisfaction (MD = -0.45; 95% CI -0.72, -0.18); and pain (MD = -1.03; 95% CI -1.34, -0.72). Women with endometriosis displayed differences (more severity) in terms of VAS scores (2 studies) for dyspareunia (MD = 1.88; 95% CI 0.38, 3.37) and chronic pelvic pain (MD = 2.92; 95% CI 1.26, 4.58); but not for dysmenorrhea. Conclusion: Non-treated women with endometriosis displayed altered sexual function as evidenced by lower scores in all FSFI domains, and severity of dyspareunia and chronic pelvic pain

Prevalence of Depression in Retirees: A Meta-Analysis

Background: Retirement is a final life stage characterized by the ceasing of work and the loss of a routine, social relations, role, status, accomplishments, and aspirations, etc. Many times it is accompanied by negative feelings and can provoke different psychoemotional reactions such as depression, among others. The aim of this study is to analyze the prevalence of depression, as well as its psychoeducational approach in retirees. Methods: A paired systematic review with meta-analysis was conducted in different databases-Medline, Scopus, CUIDEN, CINAHL, LILACS and PsycINFO. Original studies were included in English, Spanish and French that were published in the last 10 years, and which approached depression in retirees. Results: A total of 11 articles were selected after applying inclusion and exclusion criteria. The mean value of the prevalence levels of depression in retirees obtained in the meta-analysis was 28%. Depression is more frequent in retirees, with mandatory retirement, retirement due to illness, and anticipated retirement presenting higher levels of this disease. The health role in the psychoeducational approach is highlighted in 41.6% (n = 5). Conclusions: With almost one-third of retirees suffering from depression, it is necessary to implement prevention and early detection measures to approach a public health problem

Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence

Objective: the goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of posttransplant tumor relapse and factors related to this complication. Design: retrospective study of a consecutive series of patients having had liver transplant for HCC. Patients and methodology: transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. Results: the survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR = 1,7944) (IC 95% = 1,1332-2,8413) and the vascular invasion (OR = 6,6346) (IC 95% = 1,4624-30,1003) as risk factors of relapse. Conclusions: the liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion

Análisis arqueosismológico del conjunto arqueológico romano de Mulva- Munigua (Sevilla, España). Resultados preliminares

El conjunto arqueológico romano de Mulva-Munigua (Sevilla, España) presenta daños en las edificaciones que pueden ser interpretadas como resultado de la ocurrencia de un evento sísmico (Efectos Arqueológicos de los Terremotos: EAEs) a finales del siglo III A.D., fecha coincidente con el inicio del periodo de declive económico de este asentamiento romano. Para intentar establecer el posible origen sísmico de las deformaciones, se ha procedido al inventario y análisis de las estructuras deformadas presentes en el yacimiento. No obstante, algunas de estas deformaciones también se pueden interpretar como resultado de procesos gravitaciones asociados a la ladera Este de la colina sobre la que se sitúa parte del yacimiento. Las direcciones de máxima deformación (ey) obtenidas del análisis de EAEs indica dos direcciones preferentes de la deformación (o movimiento preferente del terreno): NNO-SSE y ENEOSO. Aunque los datos presentan una dispersión importante, se puede establecer que la orientación principal NNO-SSE es compatible con un evento sísmico situado en el borde norte del Valle del Guadalquivir. La orientación ENE-OSO podría relacionarse con un evento posterior, o más seguramente con procesos de ladera de carácter cosísmico o no.Departamento de Geología y Geoquímica, Universidad Autónoma de Madrid, EspañaDepartamento de Geología, Universidad de Alcalá, EspañaInstituto Geológico y Minero de España, EspañaDepartamento de Geología, Escuela Politécnica Superior de Ávila, Universidad Salamanca, EspañaDepartamento de Edafología, Escuela Técnica Superior de Ingenieros Agrónomos, Universidad Politécnica de Madrid, EspañaDepartamento de Geografía Física, Universidad de Sevilla, Españ

The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

Oriented cell behaviors likely have a more important role in limb bud elongation during development than previously suggested by the “growth-based morphogenesis” hypothesis

Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01)

Altres ajuts: Agustí Barnadas: Honoraria: Pfizer. Consulting or Advisory Role: Pfizer, Novartis, Eli Lilly. Speakers'Bureau: Roche, Pfizer, Novartis, Genomic Health International. Travel, Accommodations, Expenses: Roche, Pfizer; Miguel A. Seguí: Consulting or Advisory Role: Roche, Pfizer, Novartis, Amgen, Eisai, Eli Lilly. Speakers' Bureau: Roche, Pfizer, Amgen. Research Funding: Roche (Inst), Novartis (Inst). Travel, Accommodations, Expenses: Roche, Pfizer, Novartis, Amgen.Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P =.136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P =.0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P =.0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation

Dynamics and Mechanical Stability of the Developing Dorsoventral Organizer of the Wing Imaginal Disc

Shaping the primordia during development relies on forces and mechanisms able to control cell segregation. In the imaginal discs of Drosophila the cellular populations that will give rise to the dorsal and ventral parts on the wing blade are segregated and do not intermingle. A cellular population that becomes specified by the boundary of the dorsal and ventral cellular domains, the so-called organizer, controls this process. In this paper we study the dynamics and stability of the dorsal-ventral organizer of the wing imaginal disc of Drosophila as cell proliferation advances. Our approach is based on a vertex model to perform in silico experiments that are fully dynamical and take into account the available experimental data such as: cell packing properties, orientation of the cellular divisions, response upon membrane ablation, and robustness to mechanical perturbations induced by fast growing clones. Our results shed light on the complex interplay between the cytoskeleton mechanics, the cell cycle, the cell growth, and the cellular interactions in order to shape the dorsal-ventral organizer as a robust source of positional information and a lineage controller. Specifically, we elucidate the necessary and sufficient ingredients that enforce its functionality: distinctive mechanical properties, including increased tension, longer cell cycle duration, and a cleavage criterion that satisfies the Hertwig rule. Our results provide novel insights into the developmental mechanisms that drive the dynamics of the DV organizer and set a definition of the so-called Notch fence model in quantitative terms

Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection

ABSTRACT: Background: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb’s vulnerability and metabolic adaptation have been carried out. Results: A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports. Conclusions: This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas