Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Depressive and anxiety symptomatology among people with asthma or atopic dermatitis: A population-based investigation using the UK Biobank data.

The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (ß = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, ß = 0.30, 95% CI, 0.27,0.34; tertile 2, ß = 0.36, 95%CI, 0.32,0.39, and tertile 3, ß = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40-59 age group (ß = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (ß = 0.43, 95%CI, 0.34,0.51 and 20-39 groups (ß = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose-response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40-59) were associated with the highest increment in DAS.

Effectiveness of Panama as an intercontinental land bridge for large mammals.

Habitat fragmentation is a primary driver of wildlife loss, and establishment of biological corridors is a common strategy to mitigate this problem. A flagship example is the Mesoamerican Biological Corridor (MBC), which aims to connect protected forest areas between Mexico and Panama to allow dispersal and gene flow of forest organisms. Because forests across Central America have continued to degrade, the functioning of the MBC has been questioned, but reliable estimates of species occurrence were unavailable. Large mammals are suitable indicators of forest functioning, so we assessed their conservation status across the Isthmus of Panama, the narrowest section of the MBC. We used large-scale camera-trap surveys and hierarchical multispecies occupancy models in a Bayesian framework to estimate the occupancy of 9 medium to large mammals and developed an occupancy-weighted connectivity metric to evaluate species-specific functional connectivity. White-lipped peccary (Tayassu pecari), jaguar (Panthera onca), giant anteater (Myrmecophaga tridactyla), white-tailed deer (Odocoileus virginianus), and tapir (Tapirus bairdii) had low expected occupancy along the MBC in Panama. Puma (Puma concolor), red brocket deer (Mazama temama), ocelot (Leopardus pardalis), and collared peccary (Pecari tajacu), which are more adaptable, had higher occupancy, even in areas with low forest cover near infrastructure. However, the majority of species were subject to ≥1 gap that was larger than their known dispersal distances, suggesting poor connectivity along the MBC in Panama. Based on our results, forests in Darien, Donoso-Santa Fe, and La Amistad International Park are critical for survival of large terrestrial mammals in Panama and 2 areas need restoration.

Efectividad de Panamá como un Puente Terrestre Intercontinental para Mamíferos Mayores Resumen La fragmentación del hábitat es un causante primario de la pérdida de biodiversidad, y el establecimiento de corredores biológicos es una estrategia común para mitigar este problema. El Corredor Biológico Mesoamericano (CBM) es un ejemplo notable que pretende conectar áreas boscosas protegidas entre México y Panamá para permitir la dispersión y flujo genético de organismos del bosque. El funcionamiento del CBM se ha cuestionado debido a que la degradación de los bosques en Centroamérica continúa, pero no se dispone de estimaciones confiables de la ocurrencia de especies. Los mamíferos grandes son indicadores adecuados del funcionamiento de los bosques tropicales Por lo tanto evaluamos su estado de conservación en el Istmo de Panamá, la sección más angosta del CBM. Utilizamos muestreos con cámaras trampa y modelos de ocupación para múltiples especies bajo un modelo Bayesiano para estimar la ocupación de 9 especies de mamíferos medianos a grandes, y desarrollamos una métrica de conectividad ponderada por la ocupación para evaluar la conectividad funcional para cada especie. El puerco de monte (Tayassu pecari), jaguar (Panthera onca), hormiguero gigante (Myrmecophaga tridactyla), venado cola blanca (Oidocoileus virginianus), y tapir (Tapirus bairdii) presentaron una ocupación baja en el CBM en Panamá. El puma (Puma concolor), venado corzo (Mazama temama), ocelote (Leopardus pardalis) y el saino (Pecari tajacu), que son más adaptables, presentaron mayor ocupación, aún en áreas con poca cobertura boscosa, cercanas a infraestructura. Sin embargo, la mayoría de las especies estuvo sujeta a ≥ 1 vacío que era mayor que sus distancias de dispersión conocidas, lo que sugiere una conectividad pobre a lo largo del CBM en Panamá. Basados en nuestros resultados, los bosques de Darién, Donoso-Santa Fé y el Parque Internacional La Amistad son críticos para la supervivencia de mamíferos terrestres grandes en Panamá mientras que 2 áreas requieren restauración.

Effects of body size on estimation of mammalian area requirements.

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals <10 kg were underestimated by a mean approximately15%, and species weighing approximately100 kg were underestimated by approximately50% on average. Thus, we found area estimation was subject to autocorrelation-induced bias that was worse for large species. Combined with the fact that extinction risk increases as body mass increases, the allometric scaling of bias we observed suggests the most threatened species are also likely to be those with the least accurate home-range estimates. As a correction, we tested whether data thinning or autocorrelation-informed home-range estimation minimized the scaling effect of autocorrelation on area estimates. Data thinning required an approximately93% data loss to achieve statistical independence with 95% confidence and was, therefore, not a viable solution. In contrast, autocorrelation-informed home-range estimation resulted in consistently accurate estimates irrespective of mass. When relating body mass to home range size, we detected that correcting for autocorrelation resulted in a scaling exponent significantly >1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Efectos del Tamaño Corporal sobre la Estimación de los Requerimientos de Área de Mamíferos Resumen La cuantificación precisa de los requerimientos de área de una especie es un prerrequisito para que la conservación basada en áreas sea efectiva. Esto comúnmente implica la recolección de datos de rastreo de la especie de interés para después realizar análisis de la distribución local. De manera problemática, la autocorrelación en los datos de rastreo puede resultar en una subestimación grave de las necesidades de espacio. Con base en trabajos previos, formulamos una hipótesis en la que supusimos que la magnitud de la subestimación varía con la masa corporal, una relación que podría tener implicaciones serias para la conservación. Para probar esta hipótesis en mamíferos terrestres, estimamos las áreas de distribución local con las ubicaciones en GPS de 757 individuos de 61 especies de mamíferos distribuidas mundialmente con una masa corporal entre 0.4 y 4,000 kg. Después aplicamos una validación cruzada en bloque para cuantificar el sesgo en estimaciones empíricas de la distribución local. Los requerimientos de área de los mamíferos <10 kg fueron subestimados por una media ∼15% y las especies con una masa ∼100 kg fueron subestimadas en ∼50% en promedio. Por lo tanto, encontramos que la estimación del área estaba sujeta al sesgo inducido por la autocorrelación, el cual era peor para las especies de talla grande. En combinación con el hecho de que el riesgo de extinción incrementa conforme aumenta la masa corporal, el escalamiento alométrico del sesgo que observamos sugiere que la mayoría de las especies amenazadas también tienen la probabilidad de ser aquellas especies con las estimaciones de distribución local menos acertadas. Como corrección, probamos si la reducción de datos o la estimación de la distribución local informada por la autocorrelación minimizan el efecto de escalamiento que tiene la autocorrelación sobre las estimaciones de área. La reducción de datos requirió una pérdida de datos del ∼93% para lograr la independencia estadística con un 95% de confianza y por lo tanto no fue una solución viable. Al contrario, la estimación de la distribución local informada por la autocorrelación resultó en estimaciones constantemente precisas sin importar la masa corporal. Cuando relacionamos la masa corporal con el tamaño de la distribución local, detectamos que la corrección de la autocorrelación resultó en un exponente de escalamiento significativamente >1, lo que significa que el escalamiento de la relación cambió sustancialmente en el extremo superior del espectro de la masa corporal.

Non-local viscosity from the Green-Kubo formula.

We study through MD simulations the correlation matrix of the discrete transverse momentum density field in real space for an unconfined Lennard-Jones fluid at equilibrium. Mori theory predicts this correlation under the Markovian approximation from the knowledge of the non-local shear viscosity matrix, which is given in terms of a Green-Kubo formula. However, the running Green-Kubo integral for the non-local shear viscosity does not have a plateau. By using a recently proposed correction for the Green-Kubo formula that eliminates the plateau problem [Español et al., Phys. Rev. E 99, 022126 (2019)], we unambiguously obtain the actual non-local shear viscosity. The resulting Markovian equation, being local in time, is not valid for very short times. We observe that the Markovian equation with non-local viscosity gives excellent predictions for the correlation matrix from a time at which the correlation is around 80% of its initial value. A local in space approximation for the viscosity gives accurate results only after the correlation has decayed to 40% of its initial value.

Microscopic Slip Boundary Conditions in Unsteady Fluid Flows.

An algebraic tail in the Green-Kubo integral for the solid-fluid friction coefficient hampers its use in the determination of the slip length. A simple theory for discrete nonlocal hydrodynamics near parallel solid walls with extended friction forces is given. We explain the origin of the algebraic tail and give a solution of the plateau problem in the Green-Kubo expressions. We derive the slip boundary condition with a microscopic expression for the slip length and the hydrodynamic wall position, and assess it through simulations of an unsteady plug flow.

Population genetic structure and habitat connectivity for jaguar (Panthera onca) conservation in Central Belize.

BACKGROUND: Connectivity among jaguar (Panthera onca) populations will ensure natural gene flow and the long-term survival of the species throughout its range. Jaguar conservation efforts have focused primarily on connecting suitable habitat in a broad-scale. Accelerated habitat reduction, human-wildlife conflict, limited funding, and the complexity of jaguar behaviour have proven challenging to maintain connectivity between populations effectively. Here, we used non-invasive genetic sampling and individual-based conservation genetic analyses to assess genetic diversity and levels of genetic connectivity between individuals in the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We used expert knowledge and scientific literature to develop models of landscape permeability based on circuit theory with fine-scale landscape features as ecosystem types, distance to human settlements and roads to predict the most probable jaguar movement across central Belize. RESULTS: We used 12 highly polymorphic microsatellite loci to identify 50 individual jaguars. We detected high levels of genetic diversity across loci (HE = 0.61, HO = 0.55, and NA = 9.33). Using Bayesian clustering and multivariate models to assess gene flow and genetic structure, we identified one single group of jaguars (K = 1). We identified critical areas for jaguar movement that fall outside the boundaries of current protected areas in central Belize. We detected two main areas of high landscape permeability in a stretch of approximately 18 km between Sittee River Forest Reserve and Manatee Forest Reserve that may increase functional connectivity and facilitate jaguar dispersal from and to Cockscomb Basin Wildlife Sanctuary. Our analysis provides important insights on fine-scale genetic and landscape connectivity of jaguars in central Belize, an area of conservation concern. CONCLUSIONS: The results of our study demonstrate high levels of relatively recent gene flow for jaguars between two study sites in central Belize. Our landscape analysis detected corridors of expected jaguar movement between the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We highlight the importance of maintaining already established corridors and consolidating new areas that further promote jaguar movement across suitable habitat beyond the boundaries of currently protected areas. Continued conservation efforts within identified corridors will further maintain and increase genetic connectivity in central Belize.

Boundary conditions derived from a microscopic theory of hydrodynamics near solids.

The theory of nonlocal isothermal hydrodynamics near a solid object derived microscopically in the study by Camargo et al. [J. Chem. Phys. 148, 064107 (2018)] is considered under the conditions that the flow fields are of macroscopic character. We show that in the limit of macroscopic flows, a simple pillbox argument implies that the reversible and irreversible forces that the solid exerts on the fluid can be represented in terms of boundary conditions. In this way, boundary conditions are derived from the underlying microscopic dynamics of the fluid-solid system. These boundary conditions are the impenetrability condition and the Navier slip boundary condition. The Green-Kubo transport coefficients associated with the irreversible forces that the solid exert on the fluid appear naturally in the slip length. The microscopic expression for the slip length thus obtained is shown to coincide with the one provided originally by Bocquet and Barrat [Phys. Rev. E 49, 3079 (1994)].

Prediction and analysis of analytical ultracentrifugation experiments for heterogeneous macromolecules and nanoparticles based on Brownian dynamics simulation.

In the prediction of sedimentation profiles in analytical ultracentrifugation, the counterflow due to diffusion must be taken into account for a proper analysis of experimental data in the determination of molecular properties. This is usually achieved by numerical solution of the Lamm equation. This paper presents an alternative approach, in which the displacement of the solute in the cell, resulting from the opposite effects of ultracentrifugal force and diffusional drift, is described by Brownian dynamics simulation of the solute particles. The formalism is developed for heterogeneous solutes, composed of several species, and implemented in computational schemes and tools. The accuracy of the procedure is verified by comparison with other methods based on the Lamm equation, and its efficiency is illustrated. The possibilities offered by the Brownian dynamics methods in the determination of solute properties and sample composition are demonstrated.

Nanoscale hydrodynamics near solids.

Density Functional Theory (DFT) is a successful and well-established theory for the study of the structure of simple and complex fluids at equilibrium. The theory has been generalized to dynamical situations when the underlying dynamics is diffusive as in, for example, colloidal systems. However, there is no such a clear foundation for Dynamic DFT (DDFT) for the case of simple fluids in contact with solid walls. In this work, we derive DDFT for simple fluids by including not only the mass density field but also the momentum density field of the fluid. The standard projection operator method based on the Kawasaki-Gunton operator is used for deriving the equations for the average value of these fields. The solid is described as featureless under the assumption that all the internal degrees of freedom of the solid relax much faster than those of the fluid (solid elasticity is irrelevant). The fluid moves according to a set of non-local hydrodynamic equations that include explicitly the forces due to the solid. These forces are of two types, reversible forces emerging from the free energy density functional, and accounting for impenetrability of the solid, and irreversible forces that involve the velocity of both the fluid and the solid. These forces are localized in the vicinity of the solid surface. The resulting hydrodynamic equations should allow one to study dynamical regimes of simple fluids in contact with solid objects in isothermal situations.

Results of an early intervention programme for patients with bacteraemia: analysis of prognostic factors and mortality.

BACKGROUND: Bacteraemia is a common cause of morbidity and mortality in patients admitted to hospital. The aim of this study is to analyse the results of a two-year programme for the early optimisation of antibiotic treatment in patients admitted to the Costa del Sol Hospital (Marbella. Spain). METHODS: A prospective two-year cohort study was conducted, evaluating all episodes of bacteraemia at the Costa del Sol Hospital. Epidemiological and microbiological characteristics, any modification of the initial antibiotic treatment, prognostic risk stratification, early mortality related to the episode of bacteraemia, and mortality after the seventh day, were included in the analysis. RESULTS: Seven hundred seventy-three episodes of bacteraemia were treated, 61.6% males and 38.4% females. The mean age was 65.2 years. The condition was most commonly acquired in the community (41.4%). The bacteraemia was most frequently urological in nature (30.5%), and E coli was the microorganism most frequently isolated (31.6%). In 51.1% of the episodes, a modification was made to optimise the treatment. In the first week, 8.2% died from bacteraemia, and 4.5% had died when they were located. The highest rates of death were associated with older patients, nosocomial acquisition, no source, McCabe score rapidly fatal, Charlson index ≥3, Pitt index ≥3 and treatment remained unmodified. CONCLUSION: The existence of bacteraemia control programmes and teams composed of clinicians who are experienced in the treatment of infectious diseases, can improve the disease outcome by enabling more severe episodes of bacteraemia to be recognised and their empirical treatment optimised.

Equivalent seminal characteristics in human and stallion at first and second ejaculated fractions.

Sperm quality was assessed in normozoospermic human (n = 10) and Spanish breed stallion (n = 10) after sperm fractionation during ejaculation. The first ejaculated fraction was separated from the second. A third sample was reconstituted using equivalent proportion of both fractions (RAW). Fraction 1, Fraction 2 and RAW semen were incubated for 30 min at 37°C to homogenise the impact of iatrogenic damage between both species. Sperm concentration, motility and sperm DNA damage were assessed in each fraction and RAW semen. The results showed two important facts: (i) spermatozoa confined at Fraction 1 exhibit superior parameters than those included at Fraction 2 in both species, and (ii) there is a certain level of concordance between species in the proportion of benefit observed when Fraction 1 is compared to RAW semen. Altogether, these results call into question whether the standard practice of whole ejaculate collection can be considered the best strategy when using male gametes for artificial insemination. In fact, the reconstituted RAW semen exhibits poorer semen characteristics than those found in Fraction 1.

[Risk factors for fetal macrosomia in patients without gestational diabetes mellitus]. / Factores de riesgo de macrosomía fetal en pacientes sin diabetes mellitus gestacional.

BACKGROUND: Fetal macrosomia is birth weight of 4,000 grams or more, regardless of gestational age, in Mexico representing about 5.4%. Associated with multiple demographic, physiological, metabolic and genetic factors of each population. OBJECTIVE: Determine the risk factors associated with the development of fetal macrosomia in patients without gestational diabetes mellitus. METHODS: Retrospective, descriptive and comparative study of patients who came to delivery from January 2012 to June 2014, 88 patients, 23 patients with diagnosis of macrosomia, and 65 patients without macrosomia without gestational diabetes mellitus were included. RESULTS: An incidence of fetal macrosomia of 18.6%. Risk factors such as parity, history of fetal macrosomia, maternal age, maternal height more to 1.70 meters showed no difference, the percentage of overweight 105% showed 69% vs 52% on the control group and gestational diabetes screening altered that present 30.4 vs 20%. CONCLUSIONS: Increased incidence of macrosomia was demonstrated in patients with metabolic factors such as the percentage of overweight and screening altered gestational diabetes mellitus, as they showed higher prevalence in the study group, all modifiable with preconception nutritional management and during pregnancy, to reduce initial weight and weight gain, improved fasting and postprandial blood glucose in patients with positive screening and negative tolerance curve carbohydrates to maintain fetal growth curve with in the percentiles.

[Vulvar squamous cell carcinoma in young women with HPV negative]. / Carcinoma epidermoide de vulva en mujer joven con VPH negative.

BACKGROUND: The vulvar cancer is the fourth more frequent neoplasia after the endometrial, cervix and ovarian cancer. Normally, it has been related to old women of ages from 70 to 80 years old. Rarely, it has been detected cases in adult or young women. However, its incidence has been increased in the last years and in more early years. It is for this change in the incidence and its appearance in early years why a possible etiology has been looked for, opening different hypothesis that go from that related to the HPV to those that study an inflammatory chronic process as the basis for the carcinogenesis. CLINICAL CASE: In this article, it has been presented the case of a woman who is 34 years old with negative VPH that made her debut with epidermoid carcinoma of the vulva moderately different and on purpose of the case, we do a revision of the literature existent. CONCLUSIONS: Vulvar cancer diagnosed in young women as in older, but with different trends, risk factors and natural history. The case reported here escapes the theories studied so far so needed new lines of inquiry to investigate this form of presentation young woman, without HPV infection.

[Myomectomy and uterine desarterialization as conservative treatment for uterine fibroids: Review of clinic case]. / Miomectomía y desarterialización uterina como tratamiento conservador de la miomatosis de grandes elementos: reporte de un caso.

BACKGROUND: Uterine fibroids are the most common gynecological tumors; the prevalence increases with age. They can cause symptoms (20-50%). Myomectomy is an alternative for women who wish to preserve their fertility, increased risk of blood loss and longer operative time. Since 2000, a significant number of surgeons have performed occlusion of uterine arteries prior to myomectomy successfully. CASE REPORT: We report the case of a 24-year-old patient, with a history of premature birth; and starts her condition after obstetric event with abnormal uterine bleeding and postcoital bleeding, accompanied by intense, oppressive and stabbing abdominal pain and increased ab-dominal volume. At physical examination an enlarged abdominal wall by a tumor involving, abdominal pain on palpation, at the gynecological examination: frankly enlarged uterus, about 25 x 20 cm, painful and tenderness. Prior to myomectomy, uterine externalization takes place and proceeds to dearterialization of uterine arteries under the García-González technique, removing the tumor without complications, with an estimated 100 cc bleeding. The bilateral uterine artery ligation, is one of the methods used to re-duce intraoperative blood loss. It is a quick, simple technique, whose theoretical basis is that 90% of the irrigation of the uterus comes from the uterine arteries.

Human plasmacytoid dendritic cells sense lymphocytic choriomeningitis virus-infected cells in vitro.

We previously reported that exosomal transfer of hepatitis C virus (HCV) positive-strand RNA from human Huh-7 hepatoma cells to human plasmacytoid dendritic cells (pDCs) triggers pDC alpha/beta interferon (IFN-α/ß) production in a Toll-like receptor 7 (TLR7)-dependent, virus-independent manner. Here we show that human pDCs are also activated by a TLR7-dependent, virus-independent, exosomal RNA transfer mechanism by human and mouse hepatoma and nonhepatoma cells that replicate the negative-strand lymphocytic choriomeningitis virus (LCMV).

The impact of an antimicrobial stewardship programme on the use of antimicrobials and the evolution of drug resistance.

Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.

Finite element discretization of non-linear diffusion equations with thermal fluctuations.

We present a finite element discretization of a non-linear diffusion equation used in the field of critical phenomena and, more recently, in the context of dynamic density functional theory. The discretized equation preserves the structure of the continuum equation. Specifically, it conserves the total number of particles and fulfills an H-theorem as the original partial differential equation. The discretization proposed suggests a particular definition of the discrete hydrodynamic variables in microscopic terms. These variables are then used to obtain, with the theory of coarse-graining, their dynamic equations for both averages and fluctuations. The hydrodynamic variables defined in this way lead to microscopically derived hydrodynamic equations that have a natural interpretation in terms of discretization of continuum equations. Also, the theory of coarse-graining allows to discuss the introduction of thermal fluctuations in a physically sensible way. The methodology proposed for the introduction of thermal fluctuations in finite element methods is general and valid for both regular and irregular grids in arbitrary dimensions. We focus here on simulations of the Ginzburg-Landau free energy functional using both regular and irregular 1D grids. Convergence of the numerical results is obtained for the static and dynamic structure factors as the resolution of the grid is increased.

Wolbachia effects in natural populations of Chorthippus parallelus from the Pyrenean hybrid zone.

We evaluate for the first time the effect of Wolbachia infection, involving two different supergroups, on the structure and dynamics of the hybrid zone between two subspecies of Chorthippus parallelus (Orthoptera) in the Pyrenees. Wolbachia infection showed no effects on female fecundity or a slight increment in females infected by F supergroup, although in the last case it has to be well established. Cytoplasmic incompatibility (CI) is confirmed in crosses carried out in the field between individuals from a natural hybrid population. This CI, registered as the relative reduction in embryo production (sh ), was of sh = 0.355 and sh = 0.286 in unidirectional crosses involving B and F supergroups, respectively. CI also occurred in bidirectional crosses (sh = 0.147) but with a weaker intensity. The transmission rates of the two Wolbachia strains (B and F) were estimated by the optimization of a theoretical model to reach the infection frequencies observed in certain population. To fit this scenario, both supergroups should present transmission rates close to 1. Further, we have simulated the infection dynamics, and hence, the capacity of Wolbachia to structure the population of the host insects and to affect to reproduction and genetic introgression in the hybrid zone. This represents a first example of the influence of Wolbachia in an insect natural hybrid zone.

Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen.