This study presents experimental testing of samples from two uni-directional carbon fibre composite (CFC) manufactured panels to determine the factors that influence the electrical properties of CFCs ...and to also determine the temperature coefficient of resistance. The CFC panels were manufactured by two different techniques to compare the impact of the manufacturing process on the electrical properties. Various electrical conductivity measurement methods were evaluated to determine the most consistent and accurate technique. The influence of sample geometry on the measured electrical conductivity was also investigated. Thermal imaging was used to image resistive losses and illustrate the current paths through the fibres within the CFC test samples. Finally, the effects of increasing temperature on the CFC samples are presented, illustrating that CFCs have a negative temperature coefficient.
Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 ...within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB–COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 95% CI 0.8‒1.4). Among TB–COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB–COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. ...Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.
Single-cell sequencing of environmental microorganisms is an essential component of the microbial ecology toolkit. However, large-scale targeted single-cell sequencing for the whole-genome recovery ...of uncultivated eukaryotes is lagging. The key challenges are low abundance in environmental communities, large complex genomes, and cell walls that are difficult to break. We describe a pipeline composed of state-of-the art single-cell genomics tools and protocols optimized for poorly studied and uncultivated eukaryotic microorganisms that are found at low abundance. This pipeline consists of seven distinct steps, beginning with sample collection and ending with genome annotation, each equipped with quality review steps to ensure high genome quality at low cost. We tested and evaluated each step on environmental samples and cultures of early-diverging lineages of fungi and Chromista/SAR. We show that genomes produced using this pipeline are almost as good as complete reference genomes for functional and comparative genomics for environmental microbial eukaryotes.
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•We optimized single-cell methodology using a broad sample range, for EME•We combined bioinformatic and bench protocols into a concise workflow•We benchmarked the pipeline and used it on environmental samples•We selected a set of QC criteria for best genome quality prediction
Genomics ; Geomicrobiology ; Microbiology
Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used ...biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.
Objectives
To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference.
Methods
...Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated.
Results
A total of 138 patients (mean age 65, 61% male, lung
n
= 72, colorectal
n
= 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 lung, 0.66 colorectal) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway.
Conclusions
Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number.
Key Points
• WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis.
• For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar.
• Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.
Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention.
We investigated the association of 2002 ...genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using cis-pQTL Mendelian randomisation (MR) and colocalisation. Findings for proteins with support from both MR, after correction for multiple-testing, and colocalisation were replicated using two independent cancer GWAS, one of European and one of African ancestry. Proteins with evidence of prostate-specific tissue expression were additionally investigated using spatial transcriptomic data in prostate tumour tissue to assess their role in tumour aggressiveness. Finally, we mapped risk proteins to drug and ongoing clinical trials targets.
We identified 20 proteins genetically linked to prostate cancer risk (14 for overall 8 specific, 7 for aggressive 3 specific, and 8 for early onset disease 2 specific), of which the majority replicated where data were available. Among these were proteins associated with aggressive disease, such as PPA2 Odds Ratio (OR) per 1 SD increment = 2.13, 95% CI: 1.54–2.93, PYY OR = 1.87, 95% CI: 1.43–2.44 and PRSS3 OR = 0.80, 95% CI: 0.73–0.89, and those associated with early onset disease, including EHPB1 OR = 2.89, 95% CI: 1.99–4.21, POGLUT3 OR = 0.76, 95% CI: 0.67–0.86 and TPM3 OR = 0.47, 95% CI: 0.34–0.64. We confirmed an inverse association of MSMB with prostate cancer overall OR = 0.81, 95% CI: 0.80–0.82, and also found an inverse association with both aggressive OR = 0.84, 95% CI: 0.82–0.86 and early onset disease OR = 0.71, 95% CI: 0.68–0.74. Using spatial transcriptomics data, we identified MSMB as the genome-wide top-most predictive gene to distinguish benign regions from high grade cancer regions that comparatively had five-fold lower MSMB expression. Additionally, ten proteins that were associated with prostate cancer risk also mapped to existing therapeutic interventions.
Our findings emphasise the importance of proteomics for improving our understanding of prostate cancer aetiology and of opportunities for novel therapeutic interventions. Additionally, we demonstrate the added benefit of in-depth functional analyses to triangulate the role of risk proteins in the clinical aggressiveness of prostate tumours. Using these integrated methods, we identify a subset of risk proteins associated with aggressive and early onset disease as priorities for investigation for the future prevention and treatment of prostate cancer.
This work was supported by Cancer Research UK (grant no. C8221/A29017).
Abstract
Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at ...large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.
1 A unified scheme to assign pollen samples to vegetation types was used to reconstruct vegetation patterns north of 55degreesN at the last glacial maximum (LGM) and mid-Holocene (6000 years B. P.). ...The pollen data set assembled for this purpose represents a comprehensive compilation based on the work of many projects and research groups. Five tundra types (cushion forb tundra, graminoid and forb tundra, prostrate dwarf-shrub tundra, erect dwarf-shrub tundra, and low- and high-shrub tundra) were distinguished and mapped on the basis of modern pollen surface samples. The tundra-forest boundary and the distributions of boreal and temperate forest types today were realistically reconstructed. During the mid-Holocene the tundra-forest boundary was north of its present position in some regions, but the pattern of this shift was strongly asymmetrical around the pole, with the largest northward shift in central Siberia (similar to200 km), little change in Beringia, and a southward shift in Keewatin and Labrador (similar to200 km). Low- and high-shrub tundra extended farther north than today. At the LGM, forests were absent from high latitudes. Graminoid and forb tundra abutted on temperate steppe in northwestern Eurasia while prostrate dwarf-shrub, erect dwarf-shrub, and graminoid and forb tundra formed a mosaic in Beringia. Graminoid and forb tundra is restricted today and does not form a large continuous biome, but the pollen data show that it was far more extensive at the LGM, while low- and high-shrub tundra were greatly reduced, illustrating the potential for climate change to dramatically alter the relative areas occupied by different vegetation types.
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