Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy

Cost of Fire in Highrise Building

The recent Grenfell tower fire disaster in 2017 and Hackitt Review heightened the need to address the issues of fire safety regulations. However, increasing pressure to reduce building costs and to complete construction projects on time remains a major challenge. This study examines the cost of fire in high rise building projects and the implications for the professional development of quantity surveyors (QS). The methodology adopted is a case study approach drawing on the recent experience of the Grenfell tower fire disaster of 2017, an analysis of data collected on fire provision in high rise buildings using the BCIS database and a review of the RICS New Rules of Measurement (NRM). Given the significant cost of fire in high rise buildings, there is a need for adequate provision in fire protection by investing in costs in anticipation of fire during cost planning stages to significantly reduce the costs associated with the consequence and responses after a fire incident estimated to be extremely high in the case of Grenfell. The QS need to move away from ad hoc approaches adopted in pricing items specific to fire protection as part of a team of professionals and developing the required competencies will significantly reduce the risk of not pricing adequately for fire provision in the cost plan

Improved sensitivity at synchrotrons using edge illumination X-ray phase-contrast imaging

The application of the X-ray phase-contrast ‘edge illumination’ principle to the highly coherent beams available at synchrotron radiation facilities is presented here. We show that, in this configuration, the technique allows achieving unprecedented angular sensitivity, of the order of few nanoradians. The results are obtained at beamlines of two different synchrotron radiation facilities, using various experimental conditions. In particular, different detectors and X-ray energies (12 keV and 85 keV) were employed, proving the flexibility of the method and the broad range of conditions over which it can be applied. Furthermore, the quantitative separation of absorption and refraction information, and the application of the edge illumination principle in combination with computed tomography, are also demonstrated. Thanks to its extremely high phase sensitivity and its flexible applicability, this technique will both improve the image quality achievable with X-ray phase contrast imaging and allow tackling areas of application which remain unexplored until now

Phase-contrast microscopy at high x-ray energy with a laboratory setup

We report on the design and realization of an x-ray imaging system for quantitative phase-contrast microscopy at high x-ray energy with laboratory-scale instrumentation. Phase and amplitudewere separated quantitatively at x-ray energies up to 80 keV with micrometric spatial resolution. The accuracy of the results was tested against numerical simulations, and the spatial resolution was experimentally quantified by measuring a Siemens star phase object. This simple setup should find broad application in those areas of x-ray imaging where high energy and spatial resolution are simultaneously required and in those difficult cases where the sample contains materials with similar x-ray absorption

Impact of Garden-Based Youth Nutrition Intervention Programs: A Review

ABSTRACT Garden-based nutrition-education programs for youth are gaining in popularity and are viewed by many as a promising strategy for increasing preferences and improving dietary intake of fruits and vegetables. This review examines the scientific literature on garden-based youth nutrition intervention programs and the impact on nutrition-related outcomes. Studies published between 1990 and 2007 were identified through a library search of databases and an examination of reference lists of relevant publications. Studies were included if they involved children and adolescents in the United States and examined the impact of garden-based nutrition education on fruit and/or vegetable intake, willingness to taste fruits and vegetables, preferences for fruits and vegetables, or other nutrition-related outcomes. Only articles published in peer-reviewed journals in English were included in the review. Eleven studies were reviewed. Five studies took place on school grounds and were integrated into the school curriculum, three studies were conducted as part of an afterschool program, and three studies were conducted within the community. Studies included youth ranging in age from 5 to 15 years. Findings from this review suggest that garden-based nutrition intervention programs may have the potential to promote increased fruit and vegetable intake among youth and increased willingness to taste fruits and vegetables among younger children; however, empirical evidence in this area is relatively scant. Therefore, there is a need for well-designed, evidenced-based, peer-reviewed studies to determine program effectiveness and impact. Suggestions for future research directions, including intervention planning, study design, evaluation, and sustainability are provided

Genome-wide variant calling in reanalysis of exome sequencing data uncovered a pathogenic TUBB3 variant.

Almost half of all individuals affected by intellectual disability (ID) remain undiagnosed. In the Solve-RD project, exome sequencing (ES) datasets from unresolved individuals with (syndromic) ID (n = 1,472 probands) are systematically reanalyzed, starting from raw sequencing files, followed by genome-wide variant calling and new data interpretation. This strategy led to the identification of a disease-causing de novo missense variant in TUBB3 in a girl with severe developmental delay, secondary microcephaly, brain imaging abnormalities, high hypermetropia, strabismus and short stature. Interestingly, the TUBB3 variant could only be identified through reanalysis of ES data using a genome-wide variant calling approach, despite being located in protein coding sequence. More detailed analysis revealed that the position of the variant within exon 5 of TUBB3 was not targeted by the enrichment kit, although consistent high-quality coverage was obtained at this position, resulting from nearby targets that provide off-target coverage. In the initial analysis, variant calling was restricted to the exon targets ± 200 bases, allowing the variant to escape detection by the variant calling algorithm. This phenomenon may potentially occur more often, as we determined that 36 established ID genes have robust off-target coverage in coding sequence. Moreover, within these regions, for 17 genes (likely) pathogenic variants have been identified before. Therefore, this clinical report highlights that, although compute-intensive, performing genome-wide variant calling instead of target-based calling may lead to the detection of diagnostically relevant variants that would otherwise remain unnoticed

Nitrogen addition alters composition, diversity, and functioning of microbial communities in mangrove soils : an incubation experiment

Mangrove ecosystems are important for carbon storage due to their high productivity and low decomposition rates. Waterways have experienced increased nutrient loads as a result of anthropogenic activities and it is unclear how this may affect carbon and nutrient cycles in downstream mangroves that receive these nutrient-rich waters. Using a laboratory-based incubation experiment, this study aimed to assess the effects of nutrient addition on the diversity and structure of mangrove soil bacterial communities, as well as biomass and activity of the soil microbial community, under different oxygen conditions. Bacterial community diversity and composition was characterised using 16S rRNA gene sequencing and microbial activity was examined through the measurement of microbial respiration and the activities of enzymes associated with organic matter decomposition. Nitrogen addition caused clear shifts in bacterial community composition, with decreases in bacterial diversity and the abundance of sulfate-reducing bacteria. Microbial biomass also decreased with nitrogen addition under reduced oxygen incubations. Changes in bacterial community structure were accompanied by changes in the activity of some enzymes involved in carbon, nitrogen and phosphorus cycling. Under reduced oxygen conditions, nitrogen addition resulted in a significant increase in the microbial metabolic quotient but no accompanying change in microbial respiration, which was explained by a decrease in microbial biomass. The findings of this study indicate that nitrogen loading has potential implications for microbial communities and carbon and nutrient cycling in mangrove environments that warrant further investigation under field conditions

On the accuracy of language trees

Historical linguistics aims at inferring the most likely language phylogenetic tree starting from information concerning the evolutionary relatedness of languages. The available information are typically lists of homologous (lexical, phonological, syntactic) features or characters for many different languages. From this perspective the reconstruction of language trees is an example of inverse problems: starting from present, incomplete and often noisy, information, one aims at inferring the most likely past evolutionary history. A fundamental issue in inverse problems is the evaluation of the inference made. A standard way of dealing with this question is to generate data with artificial models in order to have full access to the evolutionary process one is going to infer. This procedure presents an intrinsic limitation: when dealing with real data sets, one typically does not know which model of evolution is the most suitable for them. A possible way out is to compare algorithmic inference with expert classifications. This is the point of view we take here by conducting a thorough survey of the accuracy of reconstruction methods as compared with the Ethnologue expert classifications. We focus in particular on state-of-the-art distance-based methods for phylogeny reconstruction using worldwide linguistic databases. In order to assess the accuracy of the inferred trees we introduce and characterize two generalizations of standard definitions of distances between trees. Based on these scores we quantify the relative performances of the distance-based algorithms considered. Further we quantify how the completeness and the coverage of the available databases affect the accuracy of the reconstruction. Finally we draw some conclusions about where the accuracy of the reconstructions in historical linguistics stands and about the leading directions to improve it.Comment: 36 pages, 14 figure

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans