National Guidelines for the prevention of mother-to-child transmission of HIV across Europe - how do countries differ?

Objectives: The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these. Methods: A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries. Results: Twenty-two (96%) countries supported a policy to recommend antenatal HIV screening for all pregnant women (15: opt-out strategy; 8: opt-in strategy). For HIV-positive women in whom the only indication for antiretroviral therapy (ART) was PMTCT, the recommended gestational age for commencing ART varied from 12 to 28 weeks: initiation before 19 weeks gestation was recommended in guidelines from nine countries; in France, the UK and the Netherlands, there was a wide range, from 14 to 24 weeks, whereas the Swiss and Ukrainian guidelines recommended starting at 24-28 weeks and the German/Austrian and Lithuanian at 28 weeks. Six national guidelines recommended inclusion of Zidovudine in antenatal ART regimens, and seven (37%) allowed continuation of Efavirenz for women conceiving on this drug. According to nine guidelines, zidovudine should always be used intrapartum. Eighteen national guidelines stated that HIV-positive women on successful ART can have a vaginal delivery. Viral load thresholds for vaginal delivery were <1000 copies/ml in 5 countries, <400 copies/ml in 3 and <50 copies/ml in 11 countries. Conclusion: There are important differences across Europe in national PMTCT guidelines, with most variation seen where the evidence-base remains limited. Such differences should be considered when interpreting research and surveillance finding

3OD – Once-daily (OD) TDF-containing HAART in HIV-1-infected former IVDU-patients receiving opiate substitution : efficacy, tolerability and adherence

Purpose of the study: There is a clinical need for antiretroviral therapy (ART) regimens that simplify dosing and make adherence easier for specific patient groups such as former intravenous drug users (IVDU) receiving opiate substitution. Availability of tenofovir DF (TDF) and other once-daily (OD) agents could offer a viable OD regimen. The 3OD study was designed to evaluate the use of OD HAART in IVDU patients. Methods: 3OD was a single-arm, multicentre, 48-weeks trial to assess efficacy, tolerability and adherence to a OD TDF-containing HAART regimen in former IVDU patients receiving opiate substitution. Of 67 patients enrolled, 27 were antiretroviral treatment naïve, 10 were virologically suppressed (<400 copies/mL), and 30 were re-starting HAART without prior virological failure. Opiate substitution was adjusted according to subject symptoms of opiate overdosing or withdrawal. Various methods were used to assess adherence: besides pill count, patients were asked to fill in a MASRI (Medication Adherence Self-Report Inventory) questionnaire and an electronic log pad diary. Calculation of adherence by pill count assumed that unreturned pills had been taken by the subjects. Summary of results: Overall, 55% (n = 37, ITT, M = F) of patients had viral load 100% using pill count. MASRI showed adherence rates of 80–100% in 83–85% of patients; however, 15 patients never entered any data. Diary data were entered by 57 patients; diary data were entered for fewer days than patients received treatment (mean difference 113 days, calculated from treatment start and stop dates). Conclusion: TDF in combination with other OD antiretrovirals in former IVDU patients showed comparable efficacy to that seen in the average HIV-1 infected population. However, measurement of adherence to self-administered HAART via pill count, MASRI or diary may be misleading in this population

Removal of adult cyathostomins alters faecal microbiota and promotes an inflammatory phenotype in horses

peer-reviewedThe interactions between parasitic helminths and gut microbiota are considered to be an important, although as yet incompletely understood, factor in the regulation of immunity, inflammation and a range of diseases. Infection with intestinal helminths is ubiquitous in grazing horses, with cyathostomins (about 50 species of which are recorded) predominating. Consequences of infection include both chronic effects, and an acute inflammatory syndrome, acute larval cyathostominosis, which sometimes follows removal of adult helminths by administration of anthelmintic drugs. The presence of cyathostomins as a resident helminth population of the equine gut (the “helminthome”) provides an opportunity to investigate the effect helminth infection, and its perturbation, has on both the immune system and bacterial microbiome of the gut, as well as to determine the specific mechanisms of pathophysiology involved in equine acute larval cyathostominosis. We studied changes in the faecal microbiota of two groups of horses following treatment with anthelmintics (fenbendazole or moxidectin). We found decreases in both alpha diversity and beta diversity of the faecal microbiota at Day 7 post-treatment, which were reversed by Day 14. These changes were accompanied by increases in inflammatory biomarkers. The general pattern of faecal microbiota detected was similar to that seen in the relatively few equine gut microbiome studies reported to date. We conclude that interplay between resident cyathostomin populations and the bacterial microbiota of the equine large intestine is important in maintaining homeostasis and that disturbance of this ecology can lead to gut dysbiosis and play a role in the aetiology of inflammatory conditions in the horse, including acute larval cyathostominosis

A Multiomic Approach to Investigate the Effects of a Weight Loss Program on the Intestinal Health of Overweight Horses

Obesity is endemic in human populations in the western society, and with mounting evidence that the intestinal ecological environment plays a major role in its pathogenesis, identification of therapies based on intestinal microbiota modulation are gaining attention. Obesity in companion animals is also a common clinical problem. We set out using a multidimensional approach, to determine the effectiveness and safety of a weight loss program for horses incorporating diet restriction and exercise. In addition, we aimed to investigate the effect of this program on the overall intestinal health of overweight sedentary horses. The investigation comprised of a randomized, controlled, 6-week study of 14 overweight sedentary horses and ponies who were blocked for age, gender, and breed (controls n = 7, treatment n = 7). The treatment group were fed a restricted diet (1.4% of body weight dry matter intake) and the control group a maintenance diet (2% of body weight as dry matter intake) over the study period. The treatment group were subjected to a prescribed exercise regime, while the control group were exercised to mimic foraging conditions. Several clinical measurements were taken at the start and end of the study, including morphological parameters, ultrasound measurements of subcutaneous fat, and blood pressure. Fecal microbiota analysis was performed using 16S rRNA gene sequence analysis, and fecal metabolome was analyzed using NMR spectroscopy, on samples taken at weeks 1, 3, and 6 of the study. All horses completed the study period successfully. However, two of the treatment group had to have modified exercise regimes. The treatment group showed significant weight loss (p &lt; 0.00001) and an associated decrease in waste circumference (p &lt; 0.0001) when compared with the control group. The alpha-diversity of the fecal microbiota in the treatment group showed a significant increase from the start to the end of the study period (p &lt; 0.05); however, there was no significant difference between groups at any sampling point. There were significant changes (p &lt; 0.05) in the metabolome in both groups between the start and end of the study, but not between groups at any sampling point. Finally, the resting blood pressure of all horses was significantly lower by the end of the study

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Ovarian cancer has a poor overall survival which is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naïve cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitise cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV crosstalk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients

Implementation of U.K. Earth system models for CMIP6

We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere-land-ocean-sea ice model HadGEM3-GC3.1 and the Earth system model UKESM1 which adds a carbon-nitrogen cycle and atmospheric chemistry to HadGEM3-GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions.We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3-GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation.We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility

Enhanced Molecular Typing of Treponema pallidum : Geographical Distribution of Strain Types and Association with Neurosyphilis

Strain typing is a tool for determining diversity and epidemiology of infections

Comparison of particle number size distribution trends in ground measurements and climate models

Despite a large number of studies, out of all drivers of radiative forcing, the effect of aerosols has the largest uncertainty in global climate model radiative forcing estimates. There have been studies of aerosol optical properties in climate models, but the effects of particle number size distribution need a more thorough inspection. We investigated the trends and seasonality of particle number concentrations in nucleation, Aitken, and accumulation modes at 21 measurement sites in Europe and the Arctic. For 13 of those sites, with longer measurement time series, we compared the field observations with the results from five climate models, namely EC-Earth3, ECHAM-M7, ECHAM-SALSA, NorESM1.2, and UKESM1. This is the first extensive comparison of detailed aerosol size distribution trends between in situ observations from Europe and five earth system models (ESMs). We found that the trends of particle number concentrations were mostly consistent and decreasing in both measurements and models. However, for many sites, climate models showed weaker decreasing trends than the measurements. Seasonal variability in measured number concentrations, quantified by the ratio between maximum and minimum monthly number concentration, was typically stronger at northern measurement sites compared to other locations. Models had large differences in their seasonal representation, and they can be roughly divided into two categories: for EC-Earth and NorESM, the seasonal cycle was relatively similar for all sites, and for other models the pattern of seasonality varied between northern and southern sites. In addition, the variability in concentrations across sites varied between models, some having relatively similar concentrations for all sites, whereas others showed clear differences in concentrations between remote and urban sites. To conclude, although all of the model simulations had identical input data to describe anthropogenic mass emissions, trends in differently sized particles vary among the models due to assumptions in emission sizes and differences in how models treat size-dependent aerosol processes. The inter-model variability was largest in the accumulation mode, i.e. sizes which have implications for aerosol-cloud interactions. Our analysis also indicates that between models there is a large variation in efficiency of long-range transportation of aerosols to remote locations. The differences in model results are most likely due to the more complex effect of different processes instead of one specific feature (e.g. the representation of aerosol or emission size distributions). Hence, a more detailed characterization of microphysical processes and deposition processes affecting the long-range transport is needed to understand the model variability