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Introduction: There are no data on the incidence of hypoxic-ischaemic encephalopathy (HIE) and the implementation of therapeutic hypothermia (TH) in Spain. Methods: This is a cross-sectional, national study, performed using an on-line questionnaire targeting level III neonatal care units in Spain. Participants were requested to provide data of all newborns ≥ 35 weeks of gestational age diagnosed with moderate-severe HIE over a two year-period (2012–2013), and of the implementation of TH up to June 2015. Results: All (90) contacted hospitals participated. HIE incidence rate was 0.77/1000 live newborns (95% CI 0.72–0.83). During 2012–2013, 86% of the newborns diagnosed with moderate-severe HIE received TH (active or passive). Active TH was increasingly used, from 78% in 2012 to 85% in 2013 (P = .01). Of the 14% that did not receive TH, it was mainly due to a delay in the diagnosis or inter-hospital transfer, and to the fact that the treatment was not offered. More than half (57%) were born in hospitals where TH was not provided, and passive hypothermia was used for inter-hospital patient transfer, and in 39% of the cases by inappropriately trained personnel. By June 2015, 57 out of 90 centres had implemented TH, of which 54 performed whole-body TH (using servo-controlled devices). The geographical distribution of centres with active TH, and the number of newborn that received TH, was heterogeneous. Conclusions: The incidence of moderate-severe HIE is homogeneous across Spanish territory. Significant progress is being made in the implementation of TH, however it is necessary to increase the availability of active TH between Autonomous Communities, to improve early diagnosis, and to guarantee high quality patient transfer to referral centres. Resumen: Introducción: La incidencia de la encefalopatía hipóxico-isquémica perinatal (EHI) y la implementación de la hipotermia terapéutica (HT) es desconocida en España. Método: Estudio transversal nacional en recién nacidos vivos (RNV) ≥ 35 semanas de gestación mediante cuestionario on-line en las 90 unidades neonatales de nivel iii. Se solicitaron datos de los RNV con EHI moderada-grave en los años 2012 y 2013, y de la implementación de la HT en junio del 2015. Resultados: Se recibieron datos de los 90 hospitales. La incidencia de EHI moderada-grave fue 0.77/1.000 RNV (IC del 95%, 0.72; 0.83). El 86% de los RNV con EHI recibieron HT (activa o pasiva), aumentando los que recibieron HT activa del 78% en 2012 al 85% en 2013 (p = 0.01). El 14% no recibió HT principalmente por retraso en el diagnóstico o en el traslado, o por no indicarse el tratamiento. El 57% de los RN nació en hospitales sin HT, siendo el traslado en hipotermia pasiva; en el 39% por equipos sin formación adecuada. En junio del 2015, 57/90 centros realizaban HT: 54 HT corporal total activa (todos con dispositivos servocontrolados). Existió heterogeneidad en la distribución por comunidades autónomas (CC. AA.) de centros con HT activa y en el número de RN que recibieron HT. Conclusiones: La incidencia de EHI moderada-grave es homogénea entre CC. AA. Aunque se constata un importante progreso en la implementación de la HT, es preciso mejorar la disponibilidad de HT activa entre CC. AA., así como el diagnóstico precoz y el traslado con garantías desde los centros emisores.

Objective: To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods: This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results: Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and

The purpose of this study was to assess vascular and histological alterations in two COVID-19 and three control post-mortem retinas. The macular areas of flat-mounted samples were processed for immunofluorescence. Lectin and collagen IV positive vessels were captured under confocal microscopy, and endothelium loss and tortuosity were analyzed. Expression of ACE2 (angiotensin-converting enzyme 2) (the receptor for SARS-CoV-2), Iba1 (ionized calcium-binding adaptor molecule 1) and GFAP (glial fibrillary acidic protein) were quantified in retinal sections. The number of lectin vessels in COVID-19 retinas decreased by 27% compared to the control (p < 0.01) and the tortuosity increased in COVID-19 retinas (7.3 ± 0.2) vs. control retinas (6.8 ± 0.07) (p < 0.05). Immunofluorescence analysis revealed an increase in ACE2 (2.3 ± 1.3 vs. 1.0 ± 0.1; p < 0.0001) and Iba1 expression (3.06 ± 0.6 vs. 1.0 ± 0.1; p < 0.01) in COVID-19 sections whereas no changes in GFAP were observed. Analysis of the COVID-19 macular retinal tissue suggested that endothelial cells are a preferential target of SARS-CoV-2 with subsequent changes through their ACE2 receptor expression and morphology. Thus, microglial activation was hyperactive when facing an ensuing immunological challenge after SARS-CoV-2 infection.

Abstract The effect of population size on population genetic diversity and structure has rarely been studied jointly with other factors such as the position of a population within the species’ distribution range or the presence of mutualistic partners influencing dispersal. Understanding these determining factors for genetic variation is critical for conservation of relict plants that are generally suffering from genetic deterioration. Working with 16 populations of the vulnerable relict shrub Cneorum tricoccon throughout the majority of its western Mediterranean distribution range, and using nine polymorphic microsatellite markers, we examined the effects of periphery (peripheral vs. central), population size (large vs. small), and seed disperser (introduced carnivores vs. endemic lizards) on the genetic diversity and population structure of the species. Contrasting genetic variation (HE: 0.04–0.476) was found across populations. Peripheral populations showed lower genetic diversity, but this was dependent on population size. Large peripheral populations showed high levels of genetic diversity, whereas small central populations were less diverse. Significant isolation by distance was detected, indicating that the effect of long‐distance gene flow is limited relative to that of genetic drift, probably due to high selfing rates (FIS = 0.155–0.887), restricted pollen flow, and ineffective seed dispersal. Bayesian clustering also supported the strong population differentiation and highly fragmented structure. Contrary to expectations, the type of disperser showed no significant effect on either population genetic diversity or structure. Our results challenge the idea of an effect of periphery per se that can be mainly explained by population size, drawing attention to the need of integrative approaches considering different determinants of genetic variation. Furthermore, the very low genetic diversity observed in several small populations and the strong among‐population differentiation highlight the conservation value of large populations throughout the species’ range, particularly in light of climate change and direct human threats.

Introduction: dental malocclusions are dentomaxilofacial anomalies which are found very frequently in the world population. There is registered information about the application of epidemiological indexes to identify the orthodontic treatment needs Objective: to identify the scientific production where the indexes of orthodontic treatment needs are applied. Methods: a cross-sectional and descriptive study was carried out from January to December 2013. The required information was found in Medline, PubMed and Regional Scielo databases. The data were taken in the following periods: 1975-1993, 1994-2003 and 2004-2013. The universe of study consisted of 439 abstracts and/or articles from which 334 were selected for the sample after meeting the inclusion criteria. Results: in the 1975-1993 period, 24 articles (7.2 %) were identified, 98 articles (29.3 %) in the 1994-2003 period and 212 (63.5 %) from 2004 to 2013. The papers comprising just one index amounted to 273 (81.73 %), two indexes combined in 49 (14.7 %) and 3 or more in 12 (3.6 %). Conclusions: in the first analyzed period, the most used indexes were priority orthodontic treatment index; dental esthetic index, index of orthodontic treatment need. During the second and third periods, the index of orthodontic treatment need prevailed with increased individual application of its esthetic component and the dental clinical component too. In general, this index was the most used alone or in combination, followed by the dental esthetic index.

En la cátedra de Teoría General del Derecho Penal es muy importante que el alumno desarrolle una actitud crítica a través del análisis de lo que el delito es, ya que en términos generales debe conocer tres teorías fundamentales, a saber: la Teoría de la Ley Penal, la Teoría del Delito y la Teoría de las Penas y Medidas de Seguridad, fundamentales en la enseñanza del Derecho Penal. Por lo que el presente artículo abordará la Teoría del Delito para explicar y comprender del delito sus elementos positivos y negativos: conducta y ausencia de conducta, tipicidad y atipicidad, antijuridicidad y causas de justificación, imputabilidad y causas de inimputabilidad, y la culpabilidad y causas de inculpabilidad, desde una perspectiva en el sistema jurídico mexicano actual, aplicada a la legislación penal en el Estado de México.

La creatividad es ese conjunto de capacidades y disposiciones que hacen que una persona produzca con frecuencia productos creativos. Numerosos artículos se centran en la importancia de fomentar la creatividad en contextos educativos. En el presente estudio ofrecemos una aproximación diferente puesto que la intervención, en la que se contó con 32 participantes, se lleva a cabo en un contexto de actividad extraescolar, desarrollado en el campo de las actividades artísticas y plásticas. Los participantes son diversos en capacidades, edades y procedencia desde un punto de vista sociocultural. Además y a diferencia de programas de intervención que inciden específicamente en el desarrollo de la creatividad, la presente intervención incide en la educación artística que trata el dibujo, el color, la composición y también experimenta la posibilidad plástica de otros materiales. Esta aproximación complementa otras aproximaciones más académicas y abre nuevas vías para el desarrollo de la creatividad en todos los niños y niñas. La utilización de la prueba de imaginación creativa PIC-N para valorar cambios en creatividad ha mostrado su adecuación psicométrica y su utilidad para revelar mejoras en creatividad de los participantes en El Taller, frente al grupo control (n=32).

Habitat fragmentation is one of the greatest threats to biodiversity conservation and ecosystem productivity mediated by direct human impact. Its consequences include genetic depauperation, comprising phenomena such as inbreeding depression or reduction in genetic diversity. While the capacity of wild and domestic herbivores to sustain long-distance seed dispersal has been proven, the impact of herbivore corridors in plant population genetics remains to be observed. We conducted this study in the Conquense Drove Road in Spain, where sustained use by livestock over centuries has involved transhumant herds passing twice a year en route to winter and summer pastures. We compared genetic diversity and inbreeding coefficients of Plantago lagopus populations along the drove road with populations in the surrounding agricultural matrix, at varying distances from human settlements. We observed significant differences in coefficients of inbreeding between the drove road and the agricultural matrix, as well as significant trends indicative of higher genetic diversity and population nestedness around human settlements. Trends for higher genetic diversity along drove roads may be present, although they were only marginally significant due to the available sample size. Our results illustrate a functional landscape with human settlements as dispersal hotspots, while the findings along the drove road confirm its role as a pollinator reservoir observed in other studies. Drove roads may possibly also function as linear structures that facilitate long-distance dispersal across the agricultural matrix, while local P. lagopus populations depend rather on short-distance seed dispersal. These results highlight the role of herbivore corridors for conserving the migration capacity of plants, and contribute towards understanding the role of seed dispersal and the spread of invasive species related to human activities.

The aim of this study was to investigate the presence of methicillin-resistant Staphylococcus (MRS) strains in non-managed wild ungulates present in a typical Mediterranean forest in Spain. For this purpose, nasal swabs were obtained from 139 animals: 90 wild boar (Sus scrofa), 42 red deer (Cervus elaphus) and 7 fallow deer (Dama dama), which were subsequently pre-enriched in BHI+ NaCl (6.5%) (24 h/37 °C), and then seeded in Columbia blood agar (24 h/37 °C)). The presence of the mecA gene was investigated by PCR, first from the confluent and then from individual colonies. A total of 10 mecA+ colonies were obtained of which only seven showed phenotypic resistance to oxacillin/cefoxitin (methicillin resistance). All MRS strains belonged to the Staphylococcus sciuri group. Methicillin-resistant Staphylococcus aureus (MRSA) was not detected. In addition, a significant number of MRS strains showed resistance to other antimicrobials, mainly β-lactam (7/7), gentamicin (7/7), fusidic acid (6/7) and quinupristin-dalfopristin (6/7), showing an irregular correlation with their coding genes. The genetic profiles grouped the seven strains obtained according to the bacterial species but not in relation to the animal source or the geographical place of origin. The presence of SCCmec type III, common to animals and humans, has been detected in three of the strains obtained. In conclusion, the study reveals that the wild ungulates investigated play a role as potential reservoirs of multi-resistant strains of MRS. Such strains, due to their characteristics, can be easily transferred to other wild or domestic animal species and ultimately to humans through their products.

The purpose of this study was to evaluate the long-term evolution of retinal changes in COVID-19 patients with bilateral pneumonia. A total of 17 COVID-19 patients underwent retinal imaging 6 months after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The parafoveal retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly thinner in COVID-19 patients at 6 months compared to 0 months (p = p = 0.006) but persisted significantly thickened, compared to controls (p = 0.02). The vascular density (VD) at 6 months persisted significantly decreased when compared to the control group, and no significant differences were found with the 0 months evaluation; in addition, when analyzed separately, women showed a worsening in the VD. Moreover, a significantly greater foveal area zone (FAZ) (p = 0.003) was observed in COVID-19 patients at 6 months, compared to 0 months. The cotton wool spots (CWSs) observed at baseline were no longer present at 6 months, except for one patient that developed new ones. This study demonstrates that some of the previously known microvascular alterations resulting from COVID-19, persist over time and are still evident 6 months after hospital discharge in patients who have suffered from bilateral pneumonia.

Montelukast is a weak acid drug characterized by its low solubility in the range of pH 1.2 to 4.5, which may lead to dissolution-limited absorption. The aim of this paper is to develop an in vivo predictive dissolution method for montelukast and to check its performance by establishing a level-A in vitro-in vivo correlation (IVIVC). During the development of a generic film-coated tablet formulation, two clinical trials were done with three different experimental formulations to achieve a similar formulation to the reference one. A dissolution test procedure with a flow-through cell (USP IV) was used to predict the in vivo absorption behavior. The method proposed is based on a flow rate of 5 mL/min and changes of pH mediums from 1.2 to 4.5 and then to 6.8 with standard pharmacopoeia buffers. In order to improve the dissolution of montelukast, sodium dodecyl sulfate was added to the 4.5 and 6.8 pH mediums. Dissolution profiles in from the new method were used to develop a level-A IVIVC. One-step level-A IVIVC was developed from dissolution profiles and fractions absorbed obtained by the Loo–Riegelman method. Time scaling with Levy’s plot was necessary to achieve a linear IVIVC. One-step differential equation-based IVIVC was also developed with a time-scaling function. The developed method showed similar results to a previously proposed biopredictive method for montelukast, and the added value showed the ability to discriminate among different release rates in vitro, matching the in vivo clinical bioequivalence results.

Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Therefore, the aims of this review are (i) to summarize the physicochemical and pharmacokinetic characteristics involved in the time-course of ATS, and (ii) to evaluate the major highlights and limitations of the PBPK models of ATS published so far. The PBPK models incorporate common elements related to the physicochemical aspects of ATS. However, there are important differences in relation to the analyte evaluated, the type and effect of transporters and metabolic enzymes, and the permeability value used. Additionally, this review identifies major processes (lactonization, P-gp contribution, ATS-Ca solubility, simultaneous management of multiple analytes, and experimental evidence in the target population), which would enhance the PBPK model prediction to serve as a valid tool for ATS dose optimization.

The purpose of this study was to evaluate the presence of retinal and microvascular alterations in COVID-19 patients with bilateral pneumonia due to SARS-COV-2 that required hospital admission and compare this with a cohort of age- and sex-matched controls. COVID-19 bilateral pneumonia patients underwent retinal imaging 14 days after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) measurements. Vessel density (VD) and foveal avascular zone (FAZ) area were evaluated in the superficial, deep capillary plexus (SCP, DCP), and choriocapillaris (CC). After exclusion criteria, only one eye per patient was selected, and 50 eyes (25 patients and 25 controls) were included in the analysis. COVID-19 patients presented significantly thinner ganglion cell layer (GCL) (p = 0.003) and thicker retinal nerve fiber layer (RNFL) compared to controls (p = 0.048), and this RNFL thickening was greater in COVID-19 cases with cotton wool spots (CWS), when compared with patients without CWS (p = 0.032). In both SCP and DCP, COVID-19 patients presented lower VD in the foveal region (p < 0.001) and a greater FAZ area than controls (p = 0.007). These findings suggest that thrombotic and inflammatory phenomena could be happening in the retina of COVID-19 patients. Further research is warranted to analyze the longitudinal evolution of these changes over time as well as their correlation with disease severity.

Although knowledge of the bioactive compounds produced by species inhabiting coastal waters is increasing, little is known about the bioactive potential produced by marine species occupying deeper habitats with high biodiversity and productivity. Here, we investigate about the bioactive potential of molecules produced by species that inhabit the crinoid beds, a poorly known essential fish habitat affected by trawling, wherein large amounts of commercial and noncommercial species are discarded. Based on a trawl survey conducted in 2019, 14% of the 64 species discarded on crinoid beds produce molecules with some type of bioactive potential, including; soft corals (Alcyonium palmatum); tunicates (Ascidia mentula); bony fish, such as horse mackerel (Trachurus trachurus); European hake (Merluccius merluccius); and chondrichthyans, such as small-spotted catshark (Scyliorhinus canicula). In addition, 16% of the discarded species had congeneric species that produce compounds with bioactive potential, indicating that such species might also possess similar types of bioactive molecules. Molecules with antioxidant, antitumour, antihypertensive, and antibacterial properties were the most frequent, which could provide the basis for future research aiming to discover new marine-based drugs and compounds for other human uses. Among all species or genera that produce compounds with bioactive potential, 68% presented medium or high vulnerability to trawling. Results show that the discarded catch contains many species, which produce different bioactive compounds that represent an added-value resource. These results highlight the importance of manage properly crinoid beds, to ensure that species that produce molecules with bioactive potential inhabiting these habitats are protected.

El Rincón del Ridículo como espacio intercultural de intervención se implementa como una estrategia que permite movilizar experiencias, vivencias, sentimientos mediante la realización de actividades lúdicas que implican un simbolismo creativo, fantástico e imaginativo que transportan a una dimensión espacio/temporal paralela a la real y donde los estudiantes recrean el mundo, sus normas, los estilos de convivencia; acciones que favorecen la catarsis, la imaginación, la reflexión, la creatividad, el reconocimiento y expresión de sentimientos, la aceptación del cuerpo y la persona, es decir, el bienestar subjetivo.

In Spain, a new challenge is emerging due to the increase of many recreational bicyclists on two-lane rural roads. These facilities have been mainly designed for motorized vehicles, so the coexistence of cyclists and drivers produces an impact, in terms of road safety and operation. In order to analyze the occurrence of crashes and enhance safety for bicycling, it is crucial to know the cycling volume. Standard procedures recommend using data from permanent stations and temporary short counts, but bicycle volumes are rarely monitored in rural roads. However, bicyclists tend to track their leisure and exercise activities with fitness apps that use GPS. In this context, this research aims at analyzing the daily and seasonal variability of the Strava Usage Rate (SUR), defined as the proportion of bicyclists using the Strava app along a certain segment on rural highways, to estimate the Annual Average Daily Bicycle (AADB) volume on rural roads. The findings of this study offer possible solutions to policy makers in terms of planning and design of the cycling network. Moreover, the use of crowdsourced data from the Strava app will potentially save costs to public agencies, since public data could replace costly counting campaigns.

Inter- and intra-batch variability of the quality attributes contribute to the uncertainty for demonstrating equivalent microstructure of post-approval changes and generic/hybrids of semisolid topical products. Selecting a representative sample size to describe accurately the in vitro properties of semisolids and to reach enough statistical power to demonstrate similarity between two semisolid topical products is currently challenging. The objective of this work is to establish the number of batches and units per batch to be compared based on different inter-batch and intra-batch variability to demonstrate equivalence in the physical characteristics of the products that ensure a similar microstructure of the semisolid. This investigation shows that the minimum number of batches to be compared of each product is 3 and the minimum number of units per batch could be 6 in the case of low intra- and inter-batch variability. If the products are not identical, i.e., 2.5–5% differences that are expected due to differences in the manufacturing process or the suppliers of excipients, 12 units and 6 batches are needed. If intra- or inter-batch variability is larger than 10%, the number of batches and/or the number of units needs to be increased. As the interplay between inter- and intra-batch variability is complex, the sample size required for each combination of inter- and intra-batch variability and expected difference between products can be obtained in the attached tables.

The main objective of this investigation was to develop an in vitro–in vivo correlation (IVIVC) for immediate release candesartan cilexetil formulations by designing an in vitro dissolution test to be used as development tool. The IVIVC could be used to reduce failures in future bioequivalence studies. Data from two bioequivalence studies were scaled and combined to obtain the dataset for the IVIVC. Two-step and one-step approaches were used to develop the IVIVC. Experimental solubility and permeability data confirmed candesartan cilexetil. Biopharmaceutic Classification System (BCS) class II candesartan average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed. Fractions dissolved were obtained in several conditions in USP II and IV apparatus and the results were compared calculating the f2 similarity factor. Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the products of candesartan cilexetil employed the USP IV apparatus and a three-step pH buffer change, from 1.2 to 4.5 and 6.8, with 0.2% of Tween 20. This new model was able to predict the in vivo differences in dissolution and it could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

The authors wish to make the following corrections to this paper [...]

The magnetoelastic resonance is used to monitor the precipitation reaction of calcium oxalate ( C a C 2 O 4 ) crystals in real-time, by measuring the shift of the resonance frequency caused by the mass increase on the resonator. With respect to previous work on the same matter, the novelty lies in the adoption of an amorphous ferromagnetic alloy, of composition F e 73 C r 5 S i 10 B 12 , as resonator, that replaces the commercial Metglas® 2826 alloy (composition F e 40 N i 38 M o 4 B 18 ). The enhanced corrosion resistance of this material allows it to be used in biological environments without any pre-treatment of its surface. Additionally, the measurement method, which has been specifically adapted to this application, allows quick registration of the whole resonance curve as a function of the excitation frequency, and thus enhances the resolution and decreases the detection noise. The frequency shift is calibrated by the static deposition of well-known masses of C a C 2 O 4 . The resonator dimensions have been selected to improve sensitivity. A 20 mm long, 2 mm wide and 25 μ m thick magnetoelastic resonator has been used to monitor the precipitation reaction of calcium oxalate in a 500 s time interval. The results of the detected precipitated mass when oxalic acid and calcium chloride are mixed in different concentrations (30 mM, 50 mM and 100 mM) are presented as a function of time. The results show that the sensor is capable of monitoring the precipitation reaction. The mass sensitivity obtained, and the corrosion resistance of the material, suggest that this material can perform excellently in monitoring this type of reaction.

PURPOSE:To evaluate the efficacy and safety of ranibizumab and aflibercept in the treatment of diabetic macular edema in a real world study, and to compare the two treatments with each other. METHODS:Retrospective observational study of 213 eyes from 141 patients with diabetic macular edema was completed between June 2014 and June 2016. 122 were treated with ranibizumab intravitreal injection and 91 with aflibercept intravitreal injection, with a loading phase of 3 injections and a Pro Re Nata protocol. The drug was selected by the physician and fluorescein angiography was performed by physician`s criteria. Re-treatment was performed when a decline in BCVA, an increase of central macular thickness or an increase or persistence of intraretinal fluid in OCT was observed. The primary outcome was the mean change in best corrected visual acuity at 1 year, while central macular thickness, central macular volume, the number of injections and visits were evaluated as secondary outcomes. The correlation between BCVA at 4th month visit and BCVA at 12th month visit was also evaluated. RESULTS:The mean baseline best corrected visual acuity for the eyes treated with ranibizumab was 0.55 (+/- 0.35) logMAR, and with aflibercept it was 0.48 (+/- 0.29) (P = 0.109). Best corrected visual acuity improved in both groups, and at the end of the follow-up was 0.40 (+/- 0.35) in the ranibizumab group and 0.40 (+/- 0.29) in the aflibercept group (P = 0.864). Best corrected visual acuity at 4th month visit is correlated at a high value (R = 0.789) with the one at the end of the study. No differences were found in central macular thickness, central macular volume and glycosylated hemoglobin when adjusting with baseline values. The overall number of injections was 5.77 (+/- 2.01), being 5.56 (+/- 2.0) in the ranibizumab group and 6.07 (+/- 1.99) in the aflibercept group (P = 0.069). The main outcome determining final best corrected visual acuity was the baseline best corrected visual acuity (P

The performance of magneto-impedance sensors to detect the presence and concentration of magnetic nanoparticles is investigated, using finite element calculations to directly solve Maxwell’s equations. In the case of superparamagnetic particles that are not sufficiently magnetized by an external field, it is assumed that the sensitivity of the magneto-impedance sensor to the presence of magnetic nanoparticles comes from the influence of their magnetic permeability on the sensor impedance, and not from the stray magnetic field that the particles produce. The results obtained not only justify this hypothesis, but also provide an explanation for the discrepancies found in the literature about the response of magneto-impedance sensors to the presence of magnetic nanoparticles, where some authors report an increasing magneto-impedance signal when the concentration of magnetic nanoparticles is increased, while others report a decreasing tendency. Additionally, it is demonstrated that sensors with lower magneto-impedance response display larger sensitivities to the presence of magnetic nanoparticles, indicating that the use of plain, nonmagnetic conductors as sensing materials can be beneficial, at least in the case of superparamagnetic particles insufficiently magnetized in an external magnetic field.

The study of the drivers that shape spatial genetic structure across heterogeneous landscapes is one of the main approaches used to understand population dynamics and responses in changing environments. While the Isolation-by-Distance model (IBD) assumes that genetic differentiation increases among populations with geographical distance, the Isolation-by-Resistance model (IBR) also considers geographical barriers and other landscape features that impede gene flow. On the other hand, the Isolation-by-Environment model (IBE) explains genetic differentiation through environmental differences between populations. Although spatial genetic studies have increased significantly in recent years, plants from alpine ecosystems are highly underrepresented, even though they are great suitable systems to disentangle the role of the different factors that structure genetic variation across environmental gradients. Here, we studied the spatial genetic structure of the Mediterranean alpine specialist Silene ciliata across its southernmost distribution limit. We sampled three populations across an altitudinal gradient from 1850 to 2400 m, and we replicated this sample over three mountain ranges aligned across an E-W axis in the central part of the Iberian Peninsula. We genotyped 20 individuals per population based on eight microsatellite markers and used different landscape genetic tools to infer the role of topographic and environmental factors in shaping observed patterns along the altitudinal gradient. We found a significant genetic structure among the studied Silene ciliata populations which was related to the orography and E-W configuration of the mountain ranges. IBD pattern arose as the main factor shaping population genetic differentiation. Geographical barriers between mountain ranges also affected the spatial genetic structure (IBR pattern). Although environmental variables had a significant effect on population genetic diversity parameters, no IBE pattern was found on genetic structure. Our study reveals that IBD was the driver that best explained the genetic structure, whereas environmental factors also played a role in determining genetic diversity values of this dominant plant of Mediterranean alpine environments.

PurposeTo explore the relationship between plasma C-reactive protein (CRP) levels, the main ARMS2 gene single nucleotide polymorphism (SNP), and gender in patients with neovascular age-related macular degeneration (wet AMD).MethodsOur study included 131 patients with wetAMD [age-related eye disease study (AREDS) category 4] and 153 control participants (AREDS category 1) from two Spanish retinal units. CRP levels were determined on blood samples by high-sensitivity ELISA assay. According to their CRP level, subjects were categorized into three well-established CRP categories: low (3.00 mg/L, H-CRP). Genomic DNA was extracted from oral swabs using QIAcube (Qiagen, Hilden, Germany) and the A69S; rs10490924 of ARMS2 gene was genotyped by allelic discrimination with validated TaqMan assays (Applied Biosystems, Foster City, CA, USA). Univariate and multivariate logistic regression adjusted for age was used to analyze the genomic frequencies and to calculate odds ratio (OR) using SNPStats software.ResultsConsidering CRP risk categories, H-CRP group showed a significant [OR 4.0 (1.9–8.3)] association with wetAMD compared to L-CRP group. The risk genotypes of A69S (TT) SNPs showed an association with wetAMD risk [OR 14.0 (4.8–40.8)]. Interestingly, the gender stratification of the CRP categories showed a significant increase in CRP levels in wetAMD women compared with control women [OR 6.9 (2.2–22.3)] and with wetAMD men [OR 4.6 (1.3–16.9)]. In addition, the subgroup analysis of CRP within A69S genotype and gender showed a link in women between the A69S and CRP levels in the AMD group compared to controls [OR 4.2 (1.4–12.6)].ConclusionOur study shows, for the first time, that a different genetic association related with gender could contribute to AMD risk. As a consequence, the risk of female gender in the different CRP levels and A69S SNP frequencies could be taken into consideration to the established risk relationship of high levels of CRP and its association with risk A69S genotype.

Purpose: The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations. Methods: Differences and similarities regarding solubility, permeability, dissolution, excipients and fixed-dose combination products, were identified and compared in a detailed survey of each participant’s criteria for BCS-based biowaivers. These criteria were determined based upon the participants’ respective regulatory guidance documents, policies and practices. Results: This review has, with the exception of two participants who do not accept BCS-based biowaivers, revealed that most IGDRP participants interpret the BCS principles and conditions similarly but notable differences exist in the application of these principles. Conclusion: Although many similarities exist, this review identifies several opportunities for greater convergence of regulatory requirements amongst the surveyed jurisdictions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page

¿Puede contribuir la filosofía política propuesta por Michel Foucault a la comprensión, explicación y transformación de la crisis hídrica actual en el norte de Chile? Revisando el concepto foucaultiano de gubernamentalidad, se propone contribuir al enriquecimiento de un marco teórico crítico con el fin de advertir cómo, en el contexto del capitalismo neoliberal, grandes corporaciones y mega-proyectos están interviniendo en la destrucción de ecosistemas específicos y microterritoriales de Chile, tomando como caso específico el desierto de Atacama y la cuestión del agua. El interés principal es examinar cómo el concepto de gubernamentalidad ayuda a comprender las modalidades que asume el ejercicio de poder, siendo una de ellas los gobiernos políticos que normalizan situaciones de deterioro de la naturaleza. Se expondrá, específicamente, el caso del agua en la región de Atacama, Chile.

Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness, our study highlights the need to shift the focus of fragmentation studies to the mechanisms that regulate connectivity effects, and call for caution on the use of genetic variation and plasticity to forecast population performance.

This paper investigates the patterns regarding the (un)availability of by-phrases and agent-oriented modification in adjectival passives in Spanish. Departing from the observation that adjectival participles derived from change-of-state verbs ban agent-oriented modification but those derived from stative causative verbs allow it, I put forth a novel theoretical account that derives the restrictions solely from the Aktionsart of the underlying verbal predicate, syntactically modelled and independently motivated. I extend my proposal to German and Hebrew, which display a similar behavior, and propose a parametric account for languages like Greek that freely allow by-phrases and agent-oriented modification regardless of the Aktionsart of the underlying verbal predicate.

In many micro- and nano-scale technological applications high sensitivity displacement sensors are needed, especially in ultraprecision metrology and manufacturing. In this work a new way of sensing displacement based on radio frequency resonant cavities is presented and experimentally demonstrated using a first laboratory prototype. The principle of operation of the new transducer is summarized and tested. Furthermore, an electronic interface that can be used together with the displacement transducer is designed and proved. It has been experimentally demonstrated that very high and linear sensitivity characteristic curves, in the range of some kHz/nm; are easily obtainable using this kind of transducer when it is combined with a laboratory network analyzer. In order to replace a network analyzer and provide a more affordable, self-contained, compact solution, an electronic interface has been designed, preserving as much as possible the excellent performance of the transducer, and turning it into a true standalone positioning sensor. The results obtained using the transducer together with a first prototype of the electronic interface built with cheap discrete elements show that positioning accuracies in the micrometer range are obtainable using this cost-effective solution. Better accuracies would also be attainable but using more involved and costly electronics interfaces.

The outstanding properties of selected soft magnetic materials make them successful candidates for building high performance sensors. In this paper we present our recent work regarding different sensing technologies based on the coupling of the magnetic properties of soft magnetic materials with their electric or elastic properties. In first place we report the influence on the magneto-impedance response of the thickness of Permalloy films in multilayer-sandwiched structures. An impedance change of 270% was found in the best conditions upon the application of magnetic field, with a low field sensitivity of 140%/Oe. Second, the magneto-elastic resonance of amorphous ribbons is used to demonstrate the possibility of sensitively measuring the viscosity of fluids, aimed to develop an on-line and real-time sensor capable of assessing the state of degradation of lubricant oils in machinery. A novel analysis method is shown to sensitively reveal the changes of the damping parameter of the magnetoelastic oscillations at the resonance as a function of the oil viscosity. Finally, the properties and performance of magneto-electric laminated composites of amorphous magnetic ribbons and piezoelectric polymer films are investigated, demonstrating magnetic field detection capabilities below 2.7 nT.

Demonstration of similar microstructure is essential for demonstrating the equivalence of generic topical products since the microstructure of semisolids may affect the drug release. The objective of this study was to compare the microstructure-defining physical parameters of different batches of a reference ointment containing calcipotriol and betamethasone (Daivobet 50 µg/0.5 mg/g) in order to define the acceptance range that allows concluding equivalence between these batches. Being batches of the same reference product, they are expected to be clinically equivalent and possess similar microstructure. The 90% confidence intervals for the test/reference ratio of these physical parameters were calculated with parametric and non-parametric approaches. Both methods conclude that equivalent microstructure between batches cannot be demonstrated with a reasonable sample size when the acceptance range was set at ±10%, since several physical parameters exhibit inter-batch variability >10%. An acceptance range of ±10% is therefore too strict to conclude equivalence in the microstructure of semisolid dosage forms, given the inter-batch variability observed between batches of the reference product. A wider fixed acceptance range or an acceptance range widened based on the inter-batch variability of the reference product would be advisable.

AIM: To compare the mydriatic efficacy of an ophthalmic insert (Mydriasert, MY) versus phenylephrine and tropicamide (PT) eye drops.METHODS:Two controlled, prospective, randomized, single-blind studies were performed. In the first study, a total of 80 eyes from 40 outpatient-clinic patients were analyzed. PT drops were applied to the right eye, and a MY device was inserted in the left eye for 30min. Time until maximal pupil dilation for each eye was then assessed. In the second study, 80 eyes from 80 patients undergoing cataract surgery were analyzed. Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery (40 patients), or a MY device was inserted one hour prior to surgery (40 patients).RESULTS: In the first study, MY achieved superior mydriasis compared to PT eye drops at 90min (9.04±1.33mm vs 8.78±1.37mm, P=0.012). However MY took longer than PT drops to achieve maximal dilation, and mydriasis was inferior in eyes with MY compared to PT drops at 30min (7.21±1.73mm vs 8.22±1.43mm, Pvs 8.71±1.27mm, P=0.236). In the second study, both MY and PT achieved similar levels of mydriasis at the beginning of surgery (8.75±0.76mm with MY vs 8.77±0.63mm with PT), and also at the end of surgery (7.96±1.06mm with MY vs 8.32±0.72mm with PT), with no significant difference between groups (P=0.08). MY was well tolerated and cardiovascular effects were not influenced by dilation method.CONLUSION: MY could be a safe and efficacious alternative for mydriasis. The mydriatic effect of MY is as good as conventional PT eye drops after 60min, and is superior after 90min. MY also maintains good pupil dilation during cataract surgery.

The problem of diagnostic checking is tackled from the perspective of the subspace methods. Two statistics are presented and their asymptotic distributions are derived under the null hypothesis. The procedures are devised to deal with univariate and multivariate processes, are flexible and able to separately check regular and seasonal correlations. The performance in finite samples of the proposals is illustrated via Monte Carlo simulations and two examples with real data.

In this article it is made an analysis of the influence and international scene from th e political, economic, and socio-cultural stand point and how this affects the identity of management processes. Hence the importance attached to the training process from the University in managing processes for the preservation of identity in general in a n ever changing world.

The first record of Telipogon helleri (Orchidaceae) in Mexico was in 2009. The relevance of this study is the finding and characterization of a second population of this taxon, in a new location, and the revaluation of the original population five years later of its discovery. In addition, we evaluated the new population by the Method of Evaluation of Risk of Extinction for plants in Mexico (MER-Plantas). We evaluated this species using the Risk Assessment Method of Extinction for plants in Mexico (MER- Plantas). The original population increased 1.7 % (15.38 % immatures; 84.62 % adults; n = 78 individuals), and was distributed among six phorophytes (four more than in 2009), with 73.08% of the individuals growing on twigs and with a similar number of individuals facing the different cardinal points. The new population was found in a cloud forest fragment, growing on a single phorophyte (Brunellia mexicana), consisting of 36 individuals (38.89 % immatures; 6.11 % adults), all of which were growing on the trunk and 69.44 % facing west. We suggest that T. helleri should be placed in the category of endangered (P), in the Mexican Oficial Standard for threatened ora and fauna. It is necessary to carry out demographic and molecular studies to evaluate the levels of endogamy and the genetic viability of the individuals present and to estimate the capacity for adaptation and population growth. The increase in the number of individuals in the last five years could be rapidly reversed given the adverse conditions prevailing in the habitats and localities where the two populations are found.

Teniendo en cuenta la escasez de estudios previos que permitan apreciar el efecto de la antropización sobre las comunidades de orquídeas en la Reserva de la Biosfera Sierra del Rosario, al occidente de Cuba; se procedió a realizar un estudio comparativo entre un hábitat conservado (El Salón; ES) y uno antropizado (El Taburete; ET) y se encontraron en total 27 especies de forófitos, 20 especies presentes en ET (98 forófitos) y 16 especies en ES (76 forófitos). Por lo tanto se identificaron 22 géneros de orquídeas, 26 especies y 8 326 plantas. En ES fueron 15 géneros, 18 especies y 3 251 plantas, en ET, 17 géneros, 18 especies y 5 075 plantas. Oeceoclades maculata, una especie invasora, fue la más abundante. Ambas localidades tienen una similaridad de especies de 57.14%. Las especies más dominantes fueron: Microchilus plantagineus en ES y O. maculata en ET. La dominancia en ES es de 69.27% y en ET de 81.79%. Es importante elaborar planes de manejo enfocados a controlar O. maculata en ambas áreas, y en restablecer el estrato arbóreo original de la zona antropizada.

El Programa Educa a tu hijo está dirigido a las familias con niños y niñas de 0 a 6 años. Su objetivo fundamental es contribuir al cumplimiento exitoso de esa gran responsabilidad que significa su educación. Ha sido generalizado desde 1992 en todo el país, con amplia participación comunitaria. En él se ofrecen orientaciones a los padres para el desarrollo de sus hijos, la formación de valores y el cuidado de la salud, la nutrición y la prevención de accidentes. Sin embargo, existe la necesidad de incrementar los conocimientos sobre salud bucal infantil en la familia como célula fundamental de la sociedad, para la prevención de las enfermedades bucales y el control de los factores de riesgo asociados. Es la mujer la que lleva el rol educativo fundamental, pues es quien generalmente mantiene un mayor acercamiento al niño en estos primeros años de vida. Se realizó una revisión bibliográfica a partir del análisis documental de programas y artículos relacionados con la educación infantil y la salud bucal. Se determinaron algunas consideraciones a tener en cuenta para el perfeccionamiento y actualización de los programas vigentes, haciendo énfasis en la importancia de educar y preparar a la mujer en temas de salud bucal infantil para el momento de la maternidad.The program Educate your child is directed to family with children aged 0-6 years. Its main objective is contributing to the successful outcome of that enormous responsibility the children's education is. It has been generalized since 1992 around the country, with wide community participation. In that program they offer orientation to parents for the development of their children, their value formation and health care, nutrition and accident prevention. Nonetheless, there is still the necessity of increasing knowledge on infantile oral health in the family as a main cell of the society, to prevent the oral diseases and control the associated risk facts. It is the woman who plays the main educative role, because she is the one who is nearer to the children in these first years of life. We made a bibliographic review starting from a documental analysis of programs and articles related with infantile education and oral health. We make some considerations that have to be taken into account for bettering and updating the current programs, making emphasis in the importance of educating and preparing women in infantile oral health for the moment of motherhood.

Aflatoxigenic molds can grow and produce aflatoxins on dry-fermented meat and cheese. The small, basic, cysteine-rich antifungal protein PgAFP displays a time-limited inhibitory ability against unwanted molds by increasing reactive oxygen species (ROS), which can lead to increased aflatoxin production. However, calcium abolishes the inhibitory effect of PgAFP on certain Aspergillus spp. To maximize the antifungal effect, this protein may be combined with protective cultures. Yeasts and lactic acid bacteria may counteract the impact of calcium on PgAFP fungal inhibition. The objective of this work was to study the effect of PgAFP and different combined treatments with Debaryomyces hansenii and/or Pediococcus acidilactici against growth of and aflatoxin production by an aflatoxigenic strain of Aspergillus parasiticus in both culture media and dry-fermented foods with low or high calcium levels. Aflatoxins production was increased by PgAFP but dramatically reduced by P. acidilactici in low calcium culture medium, whereas in the Ca-enriched culture medium, all treatments tested led to low aflatoxins levels. To study whether PgAFP and the protective microorganisms interfere with ROS and aflatoxin production, the relative expression of genes foxA, which is involved in peroxisomal β-oxidation, and aflP, which is required for aflatoxin biosynthesis, were evaluated. The aflatoxin overproduction induced by PgAFP seems not to be linked to peroxisomal β-oxidation. The combination of PgAFP and D. hansenii provided a successful inhibitory effect on A. parasiticus growth as well as on aflatoxin production on sliced dry-fermented sausage and cheese ripened up to 15 days, whereas P. acidilactici did not further enhance the protective effect of the two former agents. Therefore, the combined treatment of PgAFP and D. hansenii seems to provide a promising protective mean against aflatoxin-producing A. parasiticus on dry-fermented foods.

En este artículo se presentan y analizan los índices del costo de la vida de tres ciudades españolas, Palencia, Madrid y Sevilla, que cubren el periodo 1680-1800. Las contabilidades de diversos hospitales, colegios e instituciones benéficas han constituido la fuente principal para la elaboración de los referidos índices. En las tres urbes objeto de estudio los precios se comportaron de una manera bastante similar: todos los índices comparten tendencia y ciclo común y presentan un grado significativo de relación lineal entre sus tasas logarítmicas de variación. Sin embargo, también se observan diferencias significativas en los movimientos a corto y largo plazos de los precios: por un lado, las tensiones inflacionistas de la segunda mitad del siglo XVIII fueron más intensas en Palencia y en Sevilla que en la capital de la monarquía hispánica; por otro lado, en Madrid las fluctuaciones interanuales del costo de la vida fueron menos violentas que en Palencia y Sevilla. A nuestro juicio, hay evidencias que apuntan a que la singularidad de Madrid obedeció, ante todo, a la mayor cantidad de recursos que las instituciones públicas dedicaron en dicha urbe a la protección de los consumidores.In this article we present and analyze new cost of living indexes for three relevant Spanish urban centers that cover from 1680 to 1800. The accounts of several hospital, schools and charitable institutions have been used as main sources to construct these indexes. The three indexes behave in a fairly similar way. They share common trends and cycles and show a significant linear relationship among their logarithmic rates of variation. Nonetheless, some substantial differences in the short and the long term movement of prices may be observed as well. On the one hand, inflationary tensions in the second half of the eighteenth century were more intense in Palencia and Seville than in Madrid. On the other hand, yearly fluctuations in the cost of living were lower in Madrid than in Palencia and Seville. In our opinion, there is evidence suggesting that these differences were mainly due to the greater amount of resources devoted by both council and monarchy to protect consumer from rising prices in Madrid.

Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization.

Perinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE).to ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH.A systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends.from the 403 articles initially identified, 17 were finally included and critically reviewed. In infants not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive reliability was achieved at 72 hours of life (post-test probability of 95.70%, 95%CI 84.40 to 98.50%). +LR at this age was 24.30 (95%CI 5.89 to 71.30) and-LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients (59.10%, 95%CI 55.70 to 63%).This study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome.

Proponemos un nuevo procedimiento para detectar raíces unitarias basado en métodos de subespacios. Su planteamiento comporta tres aspectos fundamentales. Primero, la misma metodología se puede aplicar a series individuales o a vectores de series temporales. Segundo, utiliza una familia flexible de criterios de información, cuyas funciones de pérdida se pueden adaptar a las propiedades estadísticas de los datos. Finalmente, no requiere especificar un proceso estocástico para las series analizadas. Se demuestra la consistencia del método y los ejercicios de simulación revelan buenas propiedades en muestras finitas. Además, su aplicación práctica se ilustra mediante el análisis de varias series reales.

Stelis zootrophionoides (Orchidaceae) fue descrita recientemente a partir de material recolectado en las inmediaciones de la ciudad de San Cristóbal de Las Casas, Chiapas, México. En este trabajo se informa del descubrimiento de nuevas localidades de S. zootrophionoides y se registran formas florales (basadas en la coloración de sus flores) no conocidas previamente para la ciencia. Se modela la distribución potencial de la especie y se evalúa su riesgo de extinción a través del Método de Evaluación del Riesgo de Extinción para plantas en México (MER-Plantas). Adicionalmente se caracteriza una de sus poblaciones por ser la que enfrenta mayor riesgo. Stelis zootrophionoides ahora se conoce de cinco localidades, con un área de distribución potencial de 292 km². Se encontraron dos nuevas formas de la especie, una con flores púrpuras con manchas blancas y otra con flores amarillo-verdoso ("albinas"). De acuerdo al MER-Plantas, S. zootrophionoides se encuentra en peligro de extinción (P). En la población evaluada se encontraron 41 individuos, y está seriamente amenazada principalmente por degradación del hábitat y la expansión de la zona urbana. Se hace necesario realizar estudios demográficos y genéticos para esta especie de orquídea, así como emprender y consolidar acciones que permitan la conservación de sus poblaciones conocidas.

Silene ciliata Pourr. (Caryophyllaceae) is a species with a highly disjunct distribution which inhabits the alpine mountains of the Mediterranean Basin. We investigated the phylogeny and phylogeography of the species to (a) clarify the long-suggested division of S. ciliata into two subspecies, (b) evaluate its phylogenetic origin and (c) assess whether the species’ diversification patterns were affected by the Mediterranean relief. For this purpose, we collected DNA from 25 populations of the species that inhabit the mountains of Portugal, Spain, France, Italy, former Yugoslav Republic of Macedonia, Bulgaria and Greece and studied the plastid regions rbcL, rps16 and trnL. Major intraspecific variation was supported by all analyses, while the possibility of the existence of more varieties or subspecies was not favoured. Plastid DNA (cpDNA) evidence was in accordance with the division of S. ciliata into the two subspecies, one spreading west (Iberian Peninsula and Central Massif) and the other east of the Alps region (Italian and Balkan Peninsula). This study proposes that the species’ geographically disconnected distribution has probably derived from vicariance processes and from the Alps acting as a barrier to the species’ dispersal. The monophyletic origin of the species is highly supported. cpDNA patterns were shown independent of the chromosome evolution in the populations and could have resulted from a combination of geographic factors providing links and barriers, climatic adversities and evolutionary processes that took place during Quaternary glaciations.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that “treat and extend” and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.