Combination interventions to prevent HCV transmission among people who inject drugs: modelling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy

BackgroundInterventions such as opiate substitution therapy (OST) and high-coverage needle and syringe programs (HCNSP) cannot substantially reduce hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV antiviral treatment may prevent onward transmission. We project the impact of combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among PWID.MethodsAn HCV transmission model among PWID was used to project the combinations of OST, HCNSP, and antiviral treatment required to achieve different prevalence and incidence reductions within 10 years for 3 chronic prevalence scenarios and the impact of HCV treatment if only delivered through OST programs. Multivariate and univariate sensitivity analyses were performed.ResultsLarge reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral treatment. Scaling up OST and HCNSP substantially reduces the treatment rate required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage were increased to 40% each (no coverage at baseline), then annually treating 10, 23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60% baseline chronic HCV prevalences, respectively. Approximately 30% fewer treatments are necessary with new direct-acting antivirals. If coverage of OST and HCNSP is 50% at baseline, similar prevalence reductions require higher treatment rates for the same OST and HCNSP coverage.ConclusionsCombining antiviral treatment with OST with HCNSP is critical for achieving substantial reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are required on how best to scale up antiviral treatment and combine treatment with other interventions

Imaging characteristics of H3 K27M histone-mutant diffuse midline glioma in teenagers and adults

Background: To assess anatomical and quantitative diffusion-weighted MR imaging features in a recently classified lethal neoplasm, H3 K27M histone-mutant diffuse midline glioma [World Health Organization (WHO) IV]. / Methods: Fifteen untreated gliomas in teenagers and adults (median age 19, range, 14–64) with confirmed H3 K27M histone-mutant genotype were analysed at a national referral centre. Morphological characteristics including tumour epicentre(s), T2/FLAIR and Gadolinium enhancement patterns, calcification, haemorrhage and cyst formation were recorded. Multiple apparent diffusion coefficient (ADCmin, ADCmean) regions of interest were sited in solid tumour and normal appearing white matter (ADCNAWM) using post-processing software (Olea Sphere v2.3, Olea Medical). ADC histogram data (2nd, 5th, 10th percentile, median, mean, kurtosis, skewness) were calculated from volumetric tumour segmentations and tested against the regions of interest (ROI) data (Wilcoxon signed rank test). / Results: The median interval from imaging to tissue diagnosis was 9 (range, 0–74) days. The structural MR imaging findings varied between individuals and within tumours, often featuring signal heterogeneity on all MR sequences. All gliomas demonstrated contact with the brain midline, and 67% exhibited rim-enhancing necrosis. The mean ROI ADCmin value was 0.84 (±0.15 standard deviation, SD) ×10−3 mm2/s. In the largest tumour cross-section (excluding necrosis), an average ADCmean value of 1.12 (±0.25)×10−3 mm2/s was observed. The mean ADCmin/NAWM ratio was 1.097 (±0.149), and the mean ADCmean/NAWM ratio measured 1.466 (±0.299). With the exception of the 2nd centile, no statistical difference was observed between the regional and histogram derived ADC results. / Conclusions: H3 K27M-mutant gliomas demonstrate variable morphology and diffusivity, commonly featuring moderately low ADC values in solid tumour. Regional ADC measurements appeared representative of volumetric histogram data in this study

A novel route for volume manufacturing of hollow braided composite beam structures

This work investigates the application of a rapid variothermal moulding process for direct processing of a braided thermoplastic commingled yarn. The process uses locally controllable, responsive tooling which provides opportunities for optimum part quality and significantly reduced cycle times compared with conventional processes. The proposed process was used to directly manufacture hollow beam structures from dry commingled braided preforms. It was demonstrated that the cycle time using the rapid process was reduced by more than 90% as compared to a conventional bladder moulding process, resulting in a total cycle time of 14 min. Additionally, initial three point flexure test results indicated an improvement in the mechanical performance of the resultant parts as compared to the benchmark

Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle

Muscarinic receptors are a functionally important family of G-protein-coupled receptors. Using a combination of rapid amplification of 5′ cDNA ends and reporter gene assays, we characterized the 5′ untranslated region of the CHRM2 gene as expressed in human airway smooth muscle (HASM) cells. A splice site is present 46 bp upstream from the ATG start codon. Five exons with alternative splicing patterns are present upstream of this splice site, separated by introns ranging from 87 bp to > 145 kb. There is evidence for the gene being under the control of a TATA-less promoter with Sp1, GATA, and activator protein-2 binding sites. Multiple transcription start sites (TSSs) were identified. We identified a novel 0.5-kb hypervariable region located 648 bp upstream of the most 5′ TSS, a multiallelic (CA) tandem repeat 96 bp downstream of the most 5′ TSS, and a common C→A SNP located 136 bp upstream of the most 5′ TSS. Functional studies in primary HASM cells and the BEAS-2B cell line demonstrated highest promoter activity to be upstream of the most 3′ TSS, with potential repressor elements operating in a cell type-dependent manner, located upstream of the most 5′ TSS. We present functional data to show that the CA repeat may influence the transcription of the gene in HASM and BEAS-2B cells.peer-reviewe

Evaluation of different methods of determining the angle of attack on wind turbine blades under yawed inflow conditions

As part of the AVATAR and Mexnext projects, this study compares several methods used to derive lifting line variables from CFD simulations of the MEXICO rotor in yawed inflow. The results from six partners within the AVATAR/Mexnext consortium using five different methods of extraction were compared. Overall comparison of the induced velocities at the mid and tip parts of blade shows fairly good agreement between the tested methods, where the derived angle of attack differs within 1°, within the linear range this accounts to ˂ 10% uncertainty on the aerodynamic forces. The presented comparison shows inadequate agreement between the methods for application towards the root

Future socio-political scenarios for aquatic resources in Europe: An operationalized framework for aquaculture projections

Climate-driven changes in aquatic environments have already started to affect the European aquaculture sector’s most commercially important finfish and shellfish species. In addition to changes in water quality and temperature that can directly influence fish production by altering health status, growth performance and/or feed conversion, the aquaculture sector also faces an uncertain future in terms of production costs and returns. For example, the availability of key ingredients for fish feeds (proteins, omega-3 fatty acids) will not only depend on future changes in climate, but also on social and political factors, thereby influencing feed costs. The future cost of energy, another main expenditure for fish farms, will also depend on various factors. Finally, marketing options and subsidies will have major impacts on future aquaculture profitability. Based on the framework of four socio-political scenarios developed in the EU H2020 project climate change and European aquatic resources (CERES), we defined how these key factors for the aquaculture sector could change in the future. We then apply these scenarios to make projections of how climate change and societal and economic trends influence the mid-century (2050) profitability of European aquaculture. We used an established benchmarking approach to contrast present-day and future economic performance of “typical farms” in selected European production regions under each of the scenarios termed “World Markets,” “National Enterprise,” “Global Sustainability” and “Local Stewardship.” These scenarios were based partly on the IPCC Special Report on Emissions Scenarios framework and their representative concentration pathways (RCPs) and the widely used shared socio-economic pathways (SSPs). Together, these scenarios contrast local versus international emphasis on decision making, more versus less severe environmental change, and different consequences for producers due to future commodity prices, cash returns, and costs. The mid-century profitability of the typical farms was most sensitive to the future development of feed costs, price trends of returns, and marketing options as opposed to the direct effect of climate-driven changes in the environment. These results can inform adaptation planning by the European aquaculture sector. Moreover, applying consistent scenarios including societal and economic dimensions, facilitates regional to global comparisons of adaptation advice both within and across Blue Growth sectors

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

Pre-training Data Quality and Quantity for a Low-Resource Language: New Corpus and BERT Models for Maltese

Multilingual language models such as mBERT have seen impressive cross-lingual transfer to a variety of languages, but many languages remain excluded from these models. In this paper, we analyse the effect of pre-training with monolingual data for a low-resource language that is not included in mBERT – Maltese – with a range of pre-training set ups. We conduct evaluations with the newly pre-trained models on three morphosyntactic tasks – dependency parsing, part-of-speech tagging, and named-entity recognition – and one semantic classification task – sentiment analysis. We also present a newly created corpus for Maltese, and determine the effect that the pre-training data size and domain have on the downstream performance. Our results show that using a mixture of pre-training domains is often superior to using Wikipedia text only. We also find that a fraction of this corpus is enough to make significant leaps in performance over Wikipedia-trained models. We pre-train and compare two models on the new corpus: a monolingual BERT model trained from scratch (BERTu), and a further pretrained multilingual BERT (mBERTu). The models achieve state-of-the-art performance on these tasks, despite the new corpus being considerably smaller than typically used corpora for high-resourced languages. On average, BERTu outperforms or performs competitively with mBERTu, and the largest gains are observed for higher-level tasks