Una década después de la implantación en España de la hipotermia terapéutica en el recién nacido con encefalopatía hipóxico-isquémica perinatal / Ten years since the introduction of therapeutic hypothermia in neonates with perinatal hypoxic-ischaemic encephalopathy in Spain

Introducción: Se cumple ahora más de una década del inicio de la hipotermia terapéutica (HT)en Espa ̃na, la única intervención neuroprotectora que ha venido a ser práctica estándar en eltratamiento de la encefalopatía hipóxico-isquémica perinatal (EHI). El objetivo de este artículoes ofrecer un panorama actual y presentar las controversias surgidas alrededor de la aplicaciónde esta terapia. Desarrollo: En esta década se ha implantado con éxito la HT en la gran mayoría de los hospitalesterciarios de Espa ̃na y más del 85% de los recién nacidos con EHI moderada-grave reciben estaterapia. Entre los aspectos que pueden mejorar la eficacia de la HT están su inicio precoz dentrode las primeras 6 h de vida y el control de factores comórbidos asociados a la asfixia perinatal. En los pacientes con EHI moderada el inicio después de las 6 h parece mantener cierta eficacianeuroprotectora. Una duración de la HT mayor de 72 horas o un enfriamiento más profundo noofrecen mayor eficacia neuroprotectora y aumentan el riesgo de efectos adversos. Aspectosno bien aclarados aún son la sedación durante la HT y la aplicación de esta intervención a losneonatos con EHI leve y en otros escenarios. La información pronóstica y su marco temporal esuno de los aspectos más desafiantes. Conclusiones: La HT es universal en países con recursos económicos, aunque existen puntos de controversia no resueltos. Si bien es un tratamiento generalizado en nuestro país, falta disponerde dispositivos para el traslado de estos pacientes y su centralización.(AU)

Introduction: More than a decade has passed since therapeutic hypothermia (TH) was introduced in Spain; this is the only neuroprotective intervention that has become standard practice inthe treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). This article aims to providea current picture of the technique and to address the controversies surrounding its use. Development: In the last 10 years, TH has been successfully implemented in the vast majority of tertiary hospitals in Spain, and more than 85% of newborns with moderate or severeHIE currently receive the treatment. The factors that can improve the efficacy of TH includeearly treatment onset (first 6 hours of life) and the control of comorbid factors associated withperinatal asphyxia. In patients with moderate HIE, treatment onset after 6 hours seems to havesome neuroprotective efficacy. TH duration longer than 72 hours or deeper hypothermia do notoffer greater neuroprotective efficacy, but instead increase the risk of adverse effects. Unclarified aspects are the sedation of patients during TH, the application of the treatment in infantswith mild HIE, and its application in other scenarios. Prognostic information and time frame areone of the most challenging aspects. Conclusions: TH is universal in countries with sufficient economic resources, although certainunresolved controversies remain. While the treatment is widespread in Spain, there is a needfor cooling devices for the transfer of these patients and their centralisation.(AU)

Dynamic generation of photonic spatial quantum states with an all-fiber platform.

Photonic spatial quantum states are a subject of great interest for applications in quantum communication. One important challenge has been how to dynamically generate these states using only fiber-optical components. Here we propose and experimentally demonstrate an all-fiber system that can dynamically switch between any general transverse spatial qubit state based on linearly polarized modes. Our platform is based on a fast optical switch based on a Sagnac interferometer combined with a photonic lantern and few-mode optical fibers. We show switching times between spatial modes on the order of 5 ns and demonstrate the applicability of our scheme for quantum technologies by demonstrating a measurement-device-independent (MDI) quantum random number generator based on our platform. We run the generator continuously over 15 hours, acquiring over 13.46 Gbits of random numbers, of which we ensure that at least 60.52% are private, following the MDI protocol. Our results show the use of photonic lanterns to dynamically create spatial modes using only fiber components, which due to their robustness and integration capabilities, have important consequences for photonic classical and quantum information processing.

Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology.

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC.

Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses.

OBJECTIVE: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. METHODS: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal-fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non-isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin-eosin-stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0-3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. RESULTS: Thirty-five CMV-infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non-isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non-isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non-isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white-matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non-isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non-isolated halo, histological brain lesions did not progress with gestational age, although white-matter necrosis was more frequent, albeit non-significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). CONCLUSIONS: In CMV-infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white-matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow-up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ten years since the introduction of therapeutic hypothermia in neonates with perinatal hypoxic-ischaemic encephalopathy in Spain.

INTRODUCTION: More than a decade has passed since therapeutic hypothermia (TH) was introduced in Spain; this is the only neuroprotective intervention that has become standard practice in the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). This article aims to provide a current picture of the technique and to address the controversies surrounding its use. DEVELOPMENT: In the last 10 years, TH has been successfully implemented in the vast majority of tertiary hospitals in Spain, and more than 85% of newborns with moderate or severe HIE currently receive the treatment. The factors that can improve the efficacy of TH include early treatment onset (first 6 h of life) and the control of comorbid factors associated with perinatal asphyxia. In patients with moderate HIE, treatment onset after 6 h seems to have some neuroprotective efficacy. TH duration longer than 72 h or deeper hypothermia do not offer greater neuroprotective efficacy, but instead increase the risk of adverse effects. Controversy persists around the sedation of patients during TH, the application of the treatment in infants with mild HIE, and its application in other scenarios. Prognostic information and time frame are one of the most challenging aspects. CONCLUSIONS: TH is universal in countries with sufficient economic resources, although certain unresolved controversies remain. While the treatment is widespread in Spain, there is a need for devices for the transfer of these patients and their centralisation.

Arsenic and fluorine in groundwater in northern Mexico: spatial distribution and enrichment factors.

North-central Mexico has groundwater contaminated with arsenic (As) and fluoride (F). Based on the dispersion patterns of these solutes, their sources are linked to felsic volcanic rock fragments and secondary minerals (clays, iron oxyhydroxides) within the alluvium fill of the aquifers. However, little is known about the effect of the enrichment factors for F and As in this area. Natural enrichment factors include evaporation, Ca/Na, and competitive adsorption and desorption from solid phases. This study used 1237 groundwater quality data measurements from 305 sampling sites collected between 2012 and 2019 in the state of Durango in north-central Mexico. To determine the contribution of enrichment factors to As and F content, the study area was divided into four sections, two being in the mountainous part of the state and two in the high plateaus. The data were compared among sections and analyzed using Spearman correlation and Piper and Block diagrams. The results indicate that the main solute enrichment mechanisms are evaporation and weathering of silicates and evaporites. Among the four sections, As, pH, and HCO3 seemed not to vary, F varied slightly, and nitrate and total dissolved solids varied the most. The lack of variation in As among sections is associated to its strong adsorption to clay minerals and iron oxyhydroxides, whereas the diminished F content in the eastern sections is likely linked to the adsorption of F to precipitating calcite (since groundwater is saturated with respect to calcite (SIcalcite = 0.43) and undersaturated for fluorite (SIfluorite = - 1.16). These processes shed light on the distribution of F and As in this area, and are likely operating in other states in northern Mexico and in semi-arid areas elsewhere.

[Association between influenza vaccination and mortality due to COVID-19]. / Asociación entre la vacunación contra influenza y la mortalidad por COVID-19.

Background: It has recently been suggested that influenza vaccination may be a factor associated with decreased COVID-19 mortality. Methods: An age-matched case-control study based on hospital cases. We included subjects aged 18 years and older with a diagnosis of moderate to severe COVID-19. Infection was corroborated by RT-PCR test for SARS-COV-2. Deceased subjects were considered cases, controls were patients discharged due to improvement of acute symptoms. We used bivariate analysis to determine factors associated with death from COVID-19, and calculated odds ratios and 95% confidence intervals. Results: A total of 560 patients were included in the study, 214 (38.2%) were considered cases and 346 (61.7%) controls. A significant difference was observed with the presence of type 2 diabetes mellitus [54% vs. 39.3% between cases and controls, respectively (p=.04)] and having received influenza vaccination (p= .02). Type 2 diabetes mellitus was associated with higher COVID-19 mortality [OR 1.8 (95% CI 1.2-2.5) p=.01], whereas having been immunised against influenza in 2019 was associated with lower mortality in this group of patients [OR .6 (95% CI .4-.9) p=.02]. Conclusions: Influenza vaccination in the previous year appears to be associated with lower mortality from COVID-19; whereas type 2 diabetes mellitus is confirmed as a condition associated with higher mortality.

Promoción de la salud a través de prácticas claves en la atención integrada a las enfermedades prevalentes de la infancia (AIEPI), en profesores de educación prebásica / Health promotion through key practices in integrated attention to prevalent childhood illnesses (IMCI), in pre-basic education teachers

Introducción: la estrategia de atención integrada a las enfermedades prevalentes de la infancia (AIEPI), avanza en el concepto de integralidad de la atención de la salud, siendo una herramienta práctica, en los servicios de salud y hogar, establece máxima validez a las preocupaciones de la comunidad y del personal de salud. Objetivo: conocer la promoción de la salud a través de prácticas claves en la atención integrada a las enfermedades prevalentes de la infancia (AIEPI), en profesores de educación prebásica. Material y métodos: investigación descriptiva en población de 59 técnicos y profesionales adscritos a jardines infantiles y salas cuna, en la ciudad de Temuco, que corresponden a 23 salas cuna, que ejercen actividades laborales con lactantes de 6-12 meses. Recolección de información, y instrumento de prácticas claves propuestas por AIEPI OMS/OPS, el análisis se trabajó con estadística descriptiva e inferencia estadística, apoyándose en el software SPSS versión 24 en español. La investigación cumplió los criterios de rigor ético de Ezequiel Emanuel y la aprobación del Comité de Ética acreditado de la Universidad Mayor. Resultados: 59 personas, de sexo femenino, personal de atención en la guardería de jardines infantiles y salas cuna. La edad promedio de 40 años, promedio de 8 años de ejercicio técnico profesional. El 78% del personal de atención en la guardería, posee una jornada laboral de 9 horas diarias. Respecto a las conductas en lactancia materna un 78 %, "siempre" realiza fomento del amamantamiento y un 72,9 % "siempre" fomenta los beneficios de la lactancia materna; no obstante, en cuanto al fomento de la técnica de acople, "a veces" fomenta la técnica un 39,8 %. De la inmunización un 64,4 % del personal parvulario, "siempre fomenta la vacunación del PNI", por otro lado, un 71 % de la muestra "siempre fomenta la administración de vacunas de campaña (influenza)". De la conducta por cuadro respiratorio, un 69,5 % de la población, "siempre reconoce los signos y síntomas que alertan de un cuadro respiratorio". Conclusión: en la comunidad educativa, el uso de la estrategia desarrolla un actuar más efectivo, identificando actitudes de promoción. El tener la posibilidad de contacto diario; permite a la comunidad de prebásica dirigir su mirada hacia los problemas más relevantes y proponer estrategias para la solución en conexión con el sector salud

Introduction: the strategy of Integrated Attention to Prevalent Childhood Diseases (IMCI), advances in the concept of comprehensive health care, being a practical tool, in health and home services, giving maximum validity to concerns of the community and health personnel. Objective: to know the promotion of health through key practices in Integrated Attention to Prevalent Childhood Illnesses (IMCI), in pre-basic education teachers. Material and Methods: Descriptive research in a population of 59 technicians and professionals assigned to Kindergartens and Nursery Rooms, in the city of Temuco, corresponding to 23 Nursery Rooms, who carry out work activities with infants aged 6-12 months. Information collection and key practices instrument proposed by IMCI WHO / PAHO. The analysis was carried out with descriptive statistics and statistical inference, relying on the SPSS software version 24 in Spanish. The research met the criteria of ethical rigor of Ezequiel Emanuel and the approval of the accredited Ethics Committee of the Universidad Mayor. Results: 59 people, female, nursery care personnel from Kindergartens and Nursery Rooms. The average age of 40 years, average of 8 years of professional technical practice. 78% of the kindergarten staff have a 9-hour workday. Regarding breastfeeding behaviors, 78% "always" promote breastfeeding and 72.9% "always" promote the benefits of breastfeeding, however, regarding the promotion of the coupling technique, "a times", 39.8% promote the technique. Of the immunization, 64.4% of the kindergarten staff "always promote the PNI vaccination", on the other hand, 71% of the sample "always promote the administration of field vaccines (Influenza)". Of the behavior due to respiratory symptoms, 69.5% of the population "always recognize the signs and symptoms that warn of a respiratory condition". Conclusion: in the educational community, the use of the strategy develops a more effective action, identifying attitudes of promotion. Having the possibility of daily contact; allows the pre-basic community to direct its gaze towards the most relevant problems and propose strategies for the solution in connection with the health sector.

Polarization-independent single-photon switch based on a fiber-optical Sagnac interferometer for quantum communication networks.

An essential component of future quantum networks is an optical switch capable of dynamically routing single photons. Here we implement such a switch, based on a fiber-optical Sagnac interferometer design. The routing is implemented with a pair of fast electro-optical telecom phase modulators placed inside the Sagnac loop, such that each modulator acts on an orthogonal polarization component of the single photons, in order to yield polarization-independent capability that is crucial for several applications. We obtain an average extinction ratio of more than 19 dB between both outputs of the switch. Our experiment is built exclusively with commercial off-the-shelf components, thus allowing direct compatibility with current optical communication systems.

Ten years since the introduction of therapeutic hypothermia in neonates with perinatal hypoxic-ischaemic encephalopathy in Spain. / Una década después de la implantación en España de la hipotermia terapéutica en el recién nacido con encefalopatía hipóxico-isquémica perinatal.

INTRODUCTION: More than a decade has passed since therapeutic hypothermia (TH) was introduced in Spain; this is the only neuroprotective intervention that has become standard practice in the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE). This article aims to provide a current picture of the technique and to address the controversies surrounding its use. DEVELOPMENT: In the last 10 years, TH has been successfully implemented in the vast majority of tertiary hospitals in Spain, and more than 85% of newborns with moderate or severe HIE currently receive the treatment. The factors that can improve the efficacy of TH include early treatment onset (first 6hours of life) and the control of comorbid factors associated with perinatal asphyxia. In patients with moderate HIE, treatment onset after 6hours seems to have some neuroprotective efficacy. TH duration longer than 72hours or deeper hypothermia do not offer greater neuroprotective efficacy, but instead increase the risk of adverse effects. Unclarified aspects are the sedation of patients during TH, the application of the treatment in infants with mild HIE, and its application in other scenarios. Prognostic information and time frame are one of the most challenging aspects. CONCLUSIONS: TH is universal in countries with sufficient economic resources, although certain unresolved controversies remain. While the treatment is widespread in Spain, there is a need for cooling devices for the transfer of these patients and their centralisation.

Ceftriaxone pharmacokinetics by a sensitive and simple LC-MS/MS method: Development and application.

Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 µm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 µl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3-1000 µg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC-MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.

Efectos de una terapia basada en estimulación eléctrica funcional de activación bimanual combinada con el entrenamiento de biofeedback electromiográfico en la función motora de la extremidad superior parética en sujetos secuelados de accidente cerebrovascular / Effects of a therapy based on a functional electrical stimulation of bimanual activation combined with the training of electromyographic biofeedback on the motor function of the upper limb in subjects with stroke

Resumen Introducción El accidente cerebrovascular constituye la principal causa de muerte y discapacidad en Chile. Más del 85% de los pacientes sufren hemiplejía y más del 69% discapacidad motora funcional de las extremidades superiores. Esta alteración genera impacto en el uso de la extremidad superior, afectando las diversas actividades de la vida diaria de las personas. No existen estudios que combinen terapia de biofeedback electromiográfico y activación bimanual con estimulación eléctrica funcional en sujetos secuelados de Accidente cerebrovascular (ACV). Por esto, surge el interés de determinar el efecto que tiene un protocolo de entrenamiento basado en Estimulación Eléctrica Funcional (EEF) con activación bimanual y terapia de biofeedback en la función de la extremidad superior. Metodología: 15 sujetos secuelados de ACV entre 40 y 85 años reclutados en el área de neurorrehabilitación ambulatoria de Clínica Dávila, aleatorizados en un grupo experimental y en dos grupos controles de 5 sujetos. En cada sesión el grupo experimental entrenará quince minutos de activación bimanual con electroestimulación funcional y luego un programa de entrenamiento de biofeedback de diez minutos, mientras que el grupo control 1 y control 2 entrenaron en las mismas condiciones pero con EEF placebo y BF-EMG placebo respectivamente Resultados Existieron cambios significativos en el grupo experimental luego de la intervención. Conclusión Este estudio sugiere la estimulación eléctrica funciona y biofeedback como una herramienta para la rehabilitación de la extremidad superior paréticas en sujetos secuelados de ACV.

Introduction: Stroke is the leading cause of death and disability in Chile. More than 85% of patients suffer from hemiplegia and more than 69% functional motor disability of the upper extremities. This alteration generates an impact on the use of the upper limb, affecting the various activities of people's daily lives. There are no studies that combine electromyographic biofeedback therapy and bimanual activation with functional electrical stimulation in subjects with stroke. Therefore, there is interest in determining the effect of a training protocol based on Functional Electrical Stimulation (FES) with bimanual activation and biofeedback therapy on the function of the upper limb. Methodology: 15 subjects with stroke between 40 and 85 years recruited in the outpatients neurorehabilitation program of Clínica Dávila, randomized in an experimental group and in two control groups of 5 subjects. In each session the experimental group will train fifteen minutes of bimanual activation with functional electrostimulation and then a ten-minute biofeedback training program, while the control 1 and control 2 group trained under the same conditions but with placebo FES and placebo BF-EMG respectively. Results There were significant changes in the experimental group after the intervention. Conclusion This study suggests the electrical stimulation works and biofeedback as a tool for the rehabilitation of the upper limb in subjects with stroke.

Ampicillin and Ceftriaxone Solution Stability at Different Temperatures in Outpatient Parenteral Antimicrobial Therapy.

The inclusion of ampicillin-containing regimens in outpatient parenteral antimicrobial therapy programs (OPAT) depends upon solution stability under conditions similar to those experienced in these programs. Lack of this information could hinder the inclusion in OPAT of patients suffering from Enterococcus faecalis infective endocarditis treated with ampicillin plus ceftriaxone. The purpose of this study is to determine the stability of ampicillin and ampicillin plus ceftriaxone solutions in a simulated outpatient setting conditions. Solutions of ampicillin 24 g/liter and ampicillin 24 g/liter combined with ceftriaxone 8 g/liter were stored at 25°C ± 2°C, 30°C ± 2°C and 37°C ± 2°C for 48 h. Chemical and physical stability were evaluated at 20, 24, 30, and 48 h after manufacturing. The solutions were considered stable if the percentage of intact drug was ≥90% and color and clearness remained unchanged. After 24 h of storage at a controlled temperature, ampicillin solution in 0.9% sodium chloride was found to be stable for 30 h at 25 and 30°C and for 24 h at 37°C. In the ampicillin plus ceftriaxone combined solution, both antibiotics were found to be stable after 30 h of storage at 25 and 30°C, but at 37°C, the stability criterion was not met at any time point. Our study offers solid evidence demonstrating that the concentrations of both drugs at two of the tested temperatures (25°C and 30°C) were stable for up to 30 h. Therefore, both ampicillin alone and ampicillin plus ceftriaxone solutions would be appropriate candidates for inclusion in OPAT programs.

Bond Order Densities in Real Space.

In this contribution we introduce the concept of bond order density (BOD) on the basis of a previous work on natural adaptive orbitals. We show that BODs may be used to visualize both the global spatial distribution of the covalent bond order and its eigencomponents, which we call bond(ing) channels. BODs can be equally computed at correlated and noncorrelated levels of theory and in ground or excited states, thus offering an appealing description of bond-forming, bond-breaking, and bond-evolution processes. We show the power of the approach by examining a number of homo- and heterodiatomics, including the controversial existence of a fourth bonding component in dicarbon, by analyzing a few interesting bonding situations in polyatomics and chemical transformations, and by exemplifying exotic bonding behaviors in simple excited electronic states.

Stochastic optimization on complex variables and pure-state quantum tomography.

Real-valued functions of complex arguments violate the Cauchy-Riemann conditions and, consequently, do not have Taylor series expansion. Therefore, optimization methods based on derivatives cannot be directly applied to this class of functions. This is circumvented by mapping the problem to the field of the real numbers by considering real and imaginary parts of the complex arguments as the new independent variables. We introduce a stochastic optimization method that works within the field of the complex numbers. This has two advantages: Equations on complex arguments are simpler and easy to analyze and the use of the complex structure leads to performance improvements. The method produces a sequence of estimates that converges asymptotically in mean to the optimizer. Each estimate is generated by evaluating the target function at two different randomly chosen points. Thereby, the method allows the optimization of functions with unknown parameters. Furthermore, the method exhibits a large performance enhancement. This is demonstrated by comparing its performance with other algorithms in the case of quantum tomography of pure states. The method provides solutions which can be two orders of magnitude closer to the true minima or achieve similar results as other methods but with three orders of magnitude less resources.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Antiplatelet therapy in patients undergoing oral surgery: A systematic review and meta-analysis.

BACKGROUND: The number of patients under antiplatelet therapy (APT) continues to raise as current recommendations foster this practice. Although some recommendations to manage this treatment during oral surgery procedures exist, these have methodological shortcomings that preclude them from being conclusive. MATERIAL AND METHODS: A systematic review and meta-analysis of the best current evidence was carried out; The Cochrane Library, EMBASE and MEDLINE databases were searched for Randomized Controlled Trials (RCT) concerning patients undergoing oral surgery with APT, other relevant sources were searched manually. RESULTS: 5 RCTs met the Inclusion criteria. No clear tendency was observed (RR= 0.97 CI 95%: 0,41-2,34; p=0,09; I2= 51%), moreover, they weren't clinically significant. CONCLUSIONS: According to these findings and as bleeding is a manageable complication it seems unreasonable to undermine the APT, putting the patient in danger of a thrombotic event and its high inherent morbidity, which isn't comparable in severity and manageability to the former."