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This contribution is part of a series devoted to the phylogeny and taxonomy of powdery mildews, with an emphasis on North American taxa. An overview of Cystotheca species is given, including references to ex-type sequences or, if unavailable, proposals for representative reference sequences for phylogenetic-taxonomic purposes. The new species C. mexicana is described, based on Mexican collections on Quercus glaucoides × Quercus microphylla and Quercus liebmannii × Q. microphylla. Cystotheca lanestris is reported for the first time worldwide on Quercus laceyi (Collected in Mexico) and on Q. toumeyi (collected in Arizona, USA). Cystotheca lanestris on Q. agrifolia and on Q. cerris is reported for the first time in Mexico. Epitypes with ex-epitype sequences are designated for Cystotheca wrightii, Lanomyces tjibodensis (= C. tjibodensis), Sphaerotheca kusanoi, and S. lanestris (C. lanestris).

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Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC50 = 2.4 µM (HeLa), 1.6 µM (Vero E6)). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.

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There are two heuristic explanations proposed for the evolution of endothermy in vertebrates: a correlated response to selection for stable body temperatures, or as a correlated response to increased activity. Parental care has been suggested as a major driving force in this context given its impact on the parents' activity levels and energy budgets, and in the offspring's growth rates due to food provisioning and controlled incubation temperature. This results in a complex scenario involving multiple traits and transgenerational fitness benefits that can be hard to disentangle, quantify and ultimately test. Here we demonstrate how standard quantitative genetic models of maternal effects can be applied to study the evolution of endothermy, focusing on the interplay between daily energy expenditure (DEE) of the mother and growth rates of the offspring. Our model shows that maternal effects can dramatically exacerbate evolutionary responses to selection in comparison to regular univariate models (breeder's equation). This effect would emerge from indirect selection mediated by maternal effects concomitantly with a positive genetic covariance between DEE and growth rates. The multivariate nature of selection, which could favor a higher DEE, higher growth rates or both, might partly explain how high turnover rates were continuously favored in a self-reinforcing process. Overall, our quantitative genetic analysis provides support for the parental care hypothesis for the evolution of endothermy. We contend that much has to be gained from quantifying maternal and developmental effects on metabolic and thermoregulatory variation during adulthood.

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OBJECTIVES.: To describe the monitoring model of the Health Care Service Institutions (HCSI) of the National Health Authority (NHA) and assess the factors associated with risk-adjusted normative compliance (%RANC) within the Peruvian Health System (PHS). MATERIALS AND METHODS.: We carried out a case study of the experience of the NHA in the development and implementation of a monitoring program based on the ISO 31000-2009. With HCSI as the units of analysis, we calculated the %RANC (a scorein continuous scale ranging from 0 to 100) for comprehensive monitoring (CM) and for specific evaluations made from 2013 to 2015. A higher score in the %RANC means lower operational risk. Also, slope coefficients (ß) and their 95% confidence intervals (95% CI) were estimated using generalized linear models to estimate the association between %RANC as outcome, and health subsector, region, level of care and year, as explanatory variables. RESULTS.: The NHA made 1444 evaluations. For CM, only the Social Security Administration had higher %RANC than private centers (ß=7.7%; 95% CI 3.5 to 11.9). The HCSI of the coastal region (ß=-5.2, 95% CI -9.4 to -1.0), andean region (ß=-12.5; 95% CI -16.7 to -8.3) and jungle region (ß=-12.6, 95% CI% -17.7 to -7.6) had lower %RANC than those located in Lima Metropolitan area. %RANC was higher in 2015 than 2013 (ß=10.8; 95% CI 6.4 to 15.3). CONCLUSIONS.: The %RANC differs by health subsector, region and year of supervision. For CM, the HCSI in the Social Security Administration and in the Lima Metropolitan area had better scores, and scores improved over time. The implementation of actions aimed at improving %RANC in order to foster the full exercise of health rights in the PHS is suggested.

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RESUMEN Objetivos. Describir el modelo de supervisión de las Instituciones Prestadoras de Servicios de Salud (IPRESS) de la Superintendencia Nacional de Salud (SUSALUD) y evaluar los factores asociados al porcentaje de cumplimiento normativo ajustado a riesgo (%CNAR) en las IPRESS del Sistema de Salud Peruano (SSP). Materiales y Métodos. Se realizó un estudio de caso sobre el desarrollo e implementación de un modelo de supervisión ajustado a riesgo basado en la norma ISO 31000-2009. Con la IPRESS como unidad de análisis, se calcularon los %CNAR (un puntaje continuo entre 0 a 100) de las supervisiones integrales (SI) y supervisiones selectivas efectuadas durante los años 2013 al 2015. Un mayor %CNAR implica un menor riesgo operacional. Se estimaron coeficientes β con IC95% mediante modelos lineales generalizados para valorar la asociación entre el %CNAR (variable de respuesta) y el subsector, la región, el nivel de complejidad y el año de supervisión (variables de exposición). Resultados. Se ejecutaron 1444 supervisiones. En las SI, solo la Seguridad Social en Salud (ESSALUD) tuvo mayor %CNAR que los centros privados [(β=7,7%;IC95%(3,5 a 11,9)]. Las IPRESS de la Costa [β=-5,2;IC95%(-9,4 a -1,0)], Sierra [β=-12,5;IC95%(-16,7 a -8,3)] y Selva [β=-12,6;IC95%(-17,7 a -7,6)] tuvieron menor %CNAR que aquellas ubicadas en Lima Metropolitana. El %CNAR fue superior en el año 2015 [β=10,8IC95%(6,4 a 15,3)] en relación al año 2013. Conclusiones. El %CNAR difiere por subsector, región y año de supervisión. En las SI las IPRESS supervisadas en ESSALUD, Lima Metropolitana y el año 2015, tuvieron mejores puntuaciones. Se sugiere la puesta en marcha de acciones orientadas a mejorar el %CNAR con el propósito de favorecer el ejercicio de los derechos en salud en el SSP.

ABSTRACT Objectives. To describe the monitoring model of the Health Care Service Institutions (HCSI) of the National Health Authority (NHA) and assess the factors associated with risk-adjusted normative compliance (%RANC) within the Peruvian Health System (PHS). Materials and Methods. We carried out a case study of the experience of the NHA in the development and implementation of a monitoring program based on the ISO 31000-2009. With HCSI as the units of analysis, we calculated the %RANC (a scorein continuous scale ranging from 0 to 100) for comprehensive monitoring (CM) and for specific evaluations made from 2013 to 2015. A higher score in the %RANC means lower operational risk. Also, slope coefficients (β) and their 95% confidence intervals (95% CI) were estimated using generalized linear models to estimate the association between %RANC as outcome, and health subsector, region, level of care and year, as explanatory variables. Results. The NHA made 1444 evaluations. For CM, only the Social Security Administration had higher %RANC than private centers (β=7.7%; 95% CI 3.5 to 11.9). The HCSI of the coastal region (β=-5.2, 95% CI -9.4 to -1.0), andean region (β=-12.5; 95% CI -16.7 to -8.3) and jungle region (β=-12.6, 95% CI% -17.7 to -7.6) had lower %RANC than those located in Lima Metropolitan area. %RANC was higher in 2015 than 2013 (β=10.8; 95% CI 6.4 to 15.3). Conclusions. The %RANC differs by health subsector, region and year of supervision. For CM, the HCSI in the Social Security Administration and in the Lima Metropolitan area had better scores, and scores improved over time. The implementation of actions aimed at improving %RANC in order to foster the full exercise of health rights in the PHS is suggested.

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OBJECTIVE: To examine the effect of the bivalent human papillomavirus (HPV) vaccine on miscarriage. DESIGN: Observational long term follow-up of a randomized, double blinded trial combined with an independent unvaccinated population based cohort. SETTING: Single center study in Costa Rica. PARTICIPANTS: 7466 women in the trial and 2836 women in the unvaccinated cohort enrolled at the end of the randomized trial and in parallel with the observational trial component. INTERVENTION: Women in the trial were assigned to receive three doses of bivalent HPV vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the unvaccinated cohort received (n=2836) no vaccination. MAIN OUTCOME MEASURE: Risk of miscarriage, defined by the US Centers for Disease Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed to bivalent HPV vaccination in less than 90 days and any time from vaccination compared with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated cohort. RESULTS: Of 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381 pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies, in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk of miscarriage for pregnancies conceived less than 90 days from vaccination compared with all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided P=0.436) in unadjusted analyses. Results were similar after adjusting for age at vaccination (relative risk 1.15, one sided P=0.17), age at conception (1.03, P=0.422), and calendar year (1.06, P=0.358), and in stratified analyses. Among pregnancies conceived at any time from bivalent HPV vaccination, exposure was not associated with an increased risk of miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation (relative risk 1.35, 95% confidence interval 1.02 to 1.77, one sided P=0.017). CONCLUSIONS: There is no evidence that bivalent HPV vaccination affects the risk of miscarriage for pregnancies conceived less than 90 days from vaccination. The increased risk estimate for miscarriages in a subgroup of pregnancies conceived any time after vaccination may be an artifact of a thorough set of sensitivity analyses, but since a genuine association cannot totally be ruled out, this signal should nevertheless be explored further in existing and future studies.Trial registration Clinicaltrials.gov NCT00128661 and NCT01086709.

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Most evolutionary research on biological invasions has focused on changes seen between the native and invaded range for a particular species. However, it is likely that species that live in human-modified habitats in their native range might have evolved specific adaptations to those environments, which increase the likelihood of establishment and spread in similar human-altered environments. From a quantitative genetic perspective, this hypothesis suggests that both native and introduced populations should reside at or near the same adaptive peak. Therefore, we should observe no overall changes in the G (genetic variance-covariance) matrices between native and introduced ranges, and stabilizing selection on fitness-related traits in all populations. We tested these predictions comparing three populations of the worldwide pest Myzus persicae from the Middle East (native range) and the UK and Chile (separately introduced ranges). In general, our results provide mixed support for this idea, but further comparisons of other species are needed. In particular, we found that there has been some limited evolution in the studied traits, with the Middle East population differing from the UK and Chilean populations. This was reflected in the structure of the G-matrices, in which Chile differed from both UK and Middle East populations. Furthermore, the amount of genetic variation was massively reduced in Chile in comparison with UK and Middle East populations. Finally, we found no detectable selection on any trait in the three populations, but clones from the introduced ranges started to reproduce later, were smaller, had smaller offspring, and had lower reproductive fitness than clones from the native range.

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The mathematical model for the dynamics of the hepatitis C proposed in Avendaño et al. (2002), with four populations (healthy and unhealthy hepatocytes, the viral load of the hepatitis C virus, and T killer cells), is revised. Showing that the reduced model obtained by considering only the first three of these populations, known as basic model, has two possible equilibrium states: the uninfected one where viruses are not present in the individual, and the endemic one where viruses and infected cells are present. A threshold parameter (the basic reproductive virus number) is introduced, and in terms of it, the global stability of both two possible equilibrium states is established. Other central result consists in showing, by model numerical simulations, the feasibility of monitoring liver damage caused by HCV, avoiding unnecessary biopsies and the undesirable related inconveniences/imponderables to the patient; another result gives a mathematical modelling basis to recently developed techniques for the disease assessment based essentially on viral load measurements.

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We describe the measurement of the depth of maximum, X{max}, of the longitudinal development of air showers induced by cosmic rays. Almost 4000 events above 10;{18} eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106{-21}{+35}) g/cm{2}/decade below 10{18.24+/-0.05} eV, and (24+/-3) g/cm{2}/decade above this energy. The measured shower-to-shower fluctuations decrease from about 55 to 26 g/cm{2}. The interpretation of these results in terms of the cosmic ray mass composition is briefly discussed.