Blood thicker than water: Kinship, disease prevalence and group size drive divergent patterns of infection risk in a social mammal

The importance of social- and kin-structuring of populations for the transmission of wildlife disease is widely assumed but poorly described. Social structure can help dilute risks of transmission for group members, and is relatively easy to measure, but kin-association represents a further level of population sub-structure that is harder to measure, particularly when association behaviours happen underground. Here, using epidemiological and molecular genetic data from a wild, high-density population of the European badger (Meles meles), we quantify the risks of infection with Mycobacterium bovis (the causative agent of tuberculosis) in cubs. The risk declines with increasing size of its social group, but this net dilution effect conceals divergent patterns of infection risk. Cubs only enjoy reduced risk when social groups have a higher proportion of test-negative individuals. Cubs suffer higher infection risk in social groups containing resident infectious adults, and these risks are exaggerated when cubs and infectious adults are closely related. We further identify key differences in infection risk associated with resident infectious males and females. We link our results to parent– offspring interactions and other kin-biased association, but also consider the possibility that susceptibility to infection is heritable. These patterns of infection risk help to explain the observation of a herd immunity effect in badgers following low-intensity vaccination campaigns. They also reveal kinship and kin-association to be important, and often hidden, drivers of disease transmission in social mammals

Regular consumption of black tea increases circulating kynurenine concentrations: A randomized controlled trial

AbstractBackgroundCirculating neopterin and the ratio of kynurenine to tryptophan (KYN/TRP) concentrations are biomarkers of immune activation that have been linked to cardiovascular and total mortality. Several in vitro studies indicated that tea flavonoids and other antioxidants can modulate tryptophan breakdown rates and neopterin production in immune cells. We aimed to assess the effects of regular black tea consumption on tryptophan and neopterin metabolisms in vivo.MethodsParticipants were healthy individuals, with no major illnesses and having normal to mildly elevated systolic blood pressure. They were randomly assigned to consume 3cups/day of either powdered black tea solids (tea; n=45) or a flavonoid-free caffeine-matched beverage (control; n=49). Serum concentrations of tryptophan, kynurenine and neopterin were assessed at baseline and again at 3 and 6months after daily ingestion of the respective beverage.ResultsRegular consumption of tea over 6months, compared to control, did not significantly alter neopterin (p=0.13) or tryptophan (p=0.85) concentrations, but did result in significantly higher kynurenine (p=0.016) and KYN/TRP (p=0.012). Relative to the control group, in the tea group kynurenine and KYN/TRP increased during the treatment period by 0.28μmol/L (95% CI: −0.04, 0.60) and 3.2μmol/mmol (95% CI: −1.6, 8.0), respectively at 3months, and by 0.48μmol/L (95% CI: 0.16, 0.80) and 7.5μmol/mmol (95% CI: 2.5, 12.5), respectively at 6months.ConclusionsIncreased circulation of kynurenine and KYN/TRP following regular black tea consumption may indicate enhanced tryptophan breakdown, possibly due to immune activation-induced tryptophan degrading enzyme indoleamine 2,3-dioxygenase.General significanceThe influence of black tea consumption on biomarkers of immune system activation could relate to its general health benefits. Data suggests that the net effect strongly depends on the individual immune state, being stimulatory in healthy individuals, while acting more immune dampening in situations with an inflammatory background

A Boolean-based machine learning framework identifies predictive biomarkers of HSP90-targeted therapy response in prostate cancer

Precision medicine has emerged as an important paradigm in oncology, driven by the significant heterogeneity of individual patients' tumour. A key prerequisite for effective implementation of precision oncology is the development of companion biomarkers that can predict response to anti-cancer therapies and guide patient selection for clinical trials and/or treatment. However, reliable predictive biomarkers are currently lacking for many anti-cancer therapies, hampering their clinical application. Here, we developed a novel machine learning-based framework to derive predictive multi-gene biomarker panels and associated expression signatures that accurately predict cancer drug sensitivity. We demonstrated the power of the approach by applying it to identify response biomarker panels for an Hsp90-based therapy in prostate cancer, using proteomic data profiled from prostate cancer patient-derived explants. Our approach employs a rational feature section strategy to maximise model performance, and innovatively utilizes Boolean algebra methods to derive specific expression signatures of the marker proteins. Given suitable data for model training, the approach is also applicable to other cancer drug agents in different tumour settings.Sung-Young Shin, Margaret M. Centenera, Joshua T. Hodgson, Elizabeth V. Nguyen, Lisa M. Butler, Roger J. Daly and Lan K. Nguye

The Origin and 3D Architecture of a Km-Scale Deep-Water Scour-Fill: Example From the Skoorsteenberg Fm, Karoo Basin, South Africa

Scours, and scour fields, are common features on the modern seafloor of deep-marine systems, particularly downstream of submarine channels, and in channel-lobe-transition-zones. High-resolution images of the seafloor have improved the documentation of the large scale, coalescence, and distribution of these scours in deep-marine systems. However, their scale and high aspect ratio mean they can be challenging to identify in outcrop. Here, we document a large-scale, composite erosion surface from the exhumed deep-marine stratigraphy of Unit 5 from the Permian Karoo Basin succession in South Africa, which is interpreted to be present at the end of a submarine channel. This study utilizes 24 sedimentary logs, 2 cored boreholes, and extensive palaeocurrent and thickness data across a 126 km2 study area. Sedimentary facies analysis, thickness variations and correlation panels allowed identification of a lower heterolithic-dominated part (up to 70 m thick) and an upper sandstone-dominated part (10–40 m thick) separated by an extensive erosion surface. The lower part comprises heterolithics with abundant current and sinusoidal ripples, which due to palaeocurrents, thickness trends and adjacent depositional environments is interpreted as the aggradational lobe complex fringes. The base of the upper part comprises 2-3 medium-bedded sandstone beds interpreted as precursor lobes cut by a 3–4 km wide, 1–2 km long, and up to 28 m deep, high aspect ratio (1:100) composite scour surface. The abrupt change from heterolithics to thick-bedded sandstones marks the establishment of a new sediment delivery system, which may have been triggered by an updip channel avulsion. The composite scour and subsequent sandstone fill support a change from erosion- and bypass-dominated flows to depositional flows, which might reflect increasingly sand-rich flows as a new sediment route matured. This study provides a unique outcrop example with 3D stratigraphic control of the record of a new sediment conduit, and development and fill of a large-scale composite scour surface at a channel mouth transition zone, providing a rare insight into how scours imaged on seafloor data can be filled and preserved in the rock record

The scintillation and ionization yield of liquid xenon for nuclear recoils

XENON10 is an experiment designed to directly detect particle dark matter. It is a dual phase (liquid/gas) xenon time-projection chamber with 3D position imaging. Particle interactions generate a primary scintillation signal (S1) and ionization signal (S2), which are both functions of the deposited recoil energy and the incident particle type. We present a new precision measurement of the relative scintillation yield \leff and the absolute ionization yield Q_y, for nuclear recoils in xenon. A dark matter particle is expected to deposit energy by scattering from a xenon nucleus. Knowledge of \leff is therefore crucial for establishing the energy threshold of the experiment; this in turn determines the sensitivity to particle dark matter. Our \leff measurement is in agreement with recent theoretical predictions above 15 keV nuclear recoil energy, and the energy threshold of the measurement is 4 keV. A knowledge of the ionization yield \Qy is necessary to establish the trigger threshold of the experiment. The ionization yield \Qy is measured in two ways, both in agreement with previous measurements and with a factor of 10 lower energy threshold.Comment: 8 pages, 9 figures. To be published in Nucl. Instrum. Methods

Potential role of the posterior cruciate ligament synovio-entheseal complex in joint effusion in early osteoarthritis: a magnetic resonance imaging and histological evaluation of cadaveric tissue and data from the Osteoarthritis Initiative

Objective: This study explored posterior cruciate ligament (PCL) synovio-entheseal complex (SEC) microanatomy to determine whether it may participate in the early osteoarthritis (OA) disease process. Methods: SEC microanatomy and OA features were evaluated in 14 non-arthritic cadaveric knees (mean age = 69.9) using magnetic resonance imaging (MRI) and histology. MRI images of 49 subjects selected from the progression cohort of the Osteoarthritis Initiative (OAI) were evaluated by a musculoskeletal radiologist using an original semi-quantitative method for features associated with OA at the PCL tibial enthesis. Statistical analysis was performed using chi-square and Wilcoxon signed-rank tests to evaluate associations between SEC configuration and OA features. Results: The PCL formed a SEC-like structure encompassing bone- and ligament-lining intra-articular cartilages to which the posterior root of the medial meniscus contributed. Degenerative features at the PCL-SEC included: neovascularisation (44%), enthesis chondrocyte clustering (44%), collagen matrix fissuring at the enthesis (56%) and in the PCL itself (67%), tidemark duplication (44%), bone remodelling (44%) and microscopic inflammatory changes (33%). In the OAI cohort, SEC-related pathology included bone marrow lesions (BMLs) (69%) and osteophytosis (94%) at locations that corresponded to SEC-related cartilages. Posterior joint recess effusion (49%) was linked to MRI abnormalities at PCL-SEC cartilages (χ2 = 7.27, P = 0.007). Conclusions: The PCL has a prominent SEC configuration that is associated with microscopic OA changes in aged clinically non-diseased joints. MRI determined knee OA commonly exhibited pathological features at this site which was associated with adjacent joint effusion. Thus, the PCL-SEC could play a hitherto unappreciated role in the early OA disease process

Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection.

Background: The timing of infection is closely determined in controlled human malaria infection (CHMI) studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection. The first Kenyan Challenge Study (KCS) (Pan African Clinical Trial Registry: PACTR20121100033272) was performed in 2013 with the aim of establishing the CHMI model in Kenya. This study used aseptic, cryopreserved, attenuated Plasmodium falciparum sporozoites administered by needle and syringe (PfSPZ Challenge) and was the first to evaluate parasite dynamics post-CHMI in individuals with varying degrees of prior exposure to malaria. Methods: We describe detailed serological and functional immunological responses pre- and post-CHMI for participants in the KCS and compare these with those from malaria-naïve UK volunteers who also underwent CHMI (VAC049) (ClinicalTrials.gov NCT01465048) using PfSPZ Challenge. We assessed antibody responses to three key blood-stage merozoite antigens [merozoite surface protein 1 (MSP1), apical membrane protein 1 (AMA1), and reticulocyte-binding protein homolog 5 (RH5)] and functional activity using two candidate measures of anti-merozoite immunity; the growth inhibition activity (GIA) assay and the antibody-dependent respiratory burst activity (ADRB) assay. Results:Clear serological differences were observed pre- and post-CHMI by ELISA between malaria-naïve UK volunteers in VAC049, and Kenyan volunteers who had prior malaria exposure. Antibodies to AMA1 and schizont extract correlated with parasite multiplication rate (PMR) post-CHMI in KCS. Serum from volunteer 110 in KCS, who demonstrated a dramatically reduced PMR in vivo, had no in vitro GIA prior to CHMI but the highest level of ADRB activity. A significant difference in ADRB activity was seen between KCS volunteers with minimal and definite prior exposure to malaria and significant increases were seen in ADRB activity post-CHMI in Kenyan volunteers. Quinine and atovaquone/proguanil, previously assumed to be removed by IgG purification, were identified as likely giving rise to aberrantly high in vitro GIA results. Conclusions: The ADRB activity assay is a promising functional assay that warrants further investigation as a measure of prior exposure to malaria and predictor of control of parasite growth. The CHMI model can be used to evaluate potential measures of naturally-acquired immunity to malaria

Behandeling en stigmamanagement bij opzettelijke zelfverwonding: het smalle pad tussen te veel en te weinig interveniëren

Opzettelijke zelfverwonding wordt gedefinieerd als de intentionele directe beschadiging van het eigen lichaam, zonder bewuste suïcidale intentie. De behandeling varieert van gedwongen opname in een psychiatrische instelling (in het Britse Gemenebest), tot een permissieve aanpak zonder behandeling en uiteenlopende behandelingsmogelijkheden er tussenin. Eerst wordt de gepastheid van de mate van interveniëren besproken in functie van verschillende diagnosen. Het tweede gedeelte van het artikel bespreekt het advies dat door hulpverleners verstrekt wordt aangaande de omgang met wonden en littekens en aangaande de mogelijkheden voor een (gewezen) zelfverwonder om het stigma van een deviante identiteit te vermijden. Een rondvraag bij Belgische hulpverleners bracht aan het licht dat velen onder hen adviseren om littekens te verbergen, terwijl er anderzijds aanwijzingen zijn dat niet-verbergen een teken van herstel is. Aangezien verbergen en smoesjes verzinnen ook kunnen leiden tot de instandhouding van een deviante identiteit, wordt gewezen op meer gepaste vormen van stigmamanagement