Remotely identifying potential vector habitat in areas of refugee and displaced person populations due to the Syrian civil war

Historically leishmaniasis is most prevalent in established urban centres but this research shows that refugees and, most significantly, internally displaced persons are now commonly in areas characterized by the presence of fly habitats potentially leading to higher prominence of Leishmania infection. Areas engulfed by the Syrian civil war has thus caused the dispersal of humans into previously unpopulated areas amid habitats of the sand fly Phlebotomus papatasi that hosts the parasite Leishmania. The addition of new places of exposure to this disease add to difficulties with respect to diagnosis as well as provision of care and treatment. We used geospatial methodology adapting it to remotely identifying and analyzing sand fly habitats with the aim of measuring how common it is. Our methodology helps avoid the issue of resolution in satellite imagery by measuring likelihood rather than strictly known locations. We followed up this information with spatial analysis identifying which civilian populations are most prone to sand fly exposure, and therefore leishmaniasis, due to their geographical situation. Our results suggest that those most likely to be exposed to Leishmania are internally displaced persons, those camps less likely to receive medical relief and typically having temporary residents migrating elsewhere

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

TOI-5205b: A Jupiter transiting an M dwarf near the Convective Boundary

We present the discovery of TOI-5205b, a transiting Jovian planet orbiting a solar metallicity M4V star, which was discovered using TESS photometry and then confirmed using a combination of precise radial velocities, ground-based photometry, spectra and speckle imaging. The host star TOI-5205 sits near the eponymous `Jao gap', which is the transition region between partially and fully-convective M dwarfs. TOI-5205b has one of the highest mass ratio for M dwarf planets with a mass ratio of almost 0.3$\%$, as it orbits a host star that is just $0.392 \pm 0.015$ $M_{\odot}$. Its planetary radius is $1.03 \pm 0.03~R_J$, while the mass is $1.08 \pm 0.06~M_J$. Additionally, the large size of the planet orbiting a small star results in a transit depth of $\sim 7\%$, making it one of the deepest transits of a confirmed exoplanet orbiting a main-sequence star. The large transit depth makes TOI-5205b a compelling target to probe its atmospheric properties, as a means of tracing the potential formation pathways. While there have been radial velocity-only discoveries of giant planets around mid M dwarfs, this is the first transiting Jupiter with a mass measurement discovered around such a low-mass host star. The high mass of TOI-5205b stretches conventional theories of planet formation and disk scaling relations that cannot easily recreate the conditions required to form such planets.Comment: Submitted to ApJ. Comments are welcome. arXiv admin note: text overlap with arXiv:2203.0717

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Perceived stressors of climate vulnerability across scales in the Savannah zone of Ghana: a participatory approach

Smallholder farmers in sub-Saharan Africa are confronted with climatic and non-climatic stressors. Research attention has focused on climatic stressors, such as rainfall variability, with few empirical studies exploring non-climatic stressors and how these interact with climatic stressors at multiple scales to affect food security and livelihoods. This focus on climatic factors restricts understanding of the combinations of stressors that exacerbate the vulnerability of farming households and hampers the development of holistic climate change adaptation policies. This study addresses this particular research gap by adopting a multi-scale approach to understand how climatic and non-climatic stressors vary, and interact, across three spatial scales (household, community and district levels) to influence livelihood vulnerability of smallholder farming households in the Savannah zone of northern Ghana. This study across three case study villages utilises a series of participatory tools including semi-structured interviews, key informant interviews and focus group discussions. The incidence, importance, severity and overall risk indices for stressors are calculated at the household, community, and district levels. Results show that climatic and non-climatic stressors were perceived differently; yet, there were a number of common stressors including lack of money, high cost of farm inputs, erratic rainfall, cattle destruction of crops, limited access to markets and lack of agricultural equipment that crossed all scales. Results indicate that the gender of respondents influenced the perception and severity assessment of stressors on rural livelihoods at the community level. Findings suggest a mismatch between local and district level priorities that have implications for policy and development of agricultural and related livelihoods in rural communities. Ghana’s climate change adaptation policies need to take a more holistic approach that integrates both climatic and non-climatic factors to ensure policy coherence between national climate adaptation plans and District development plans

Transcriptomic profile of host response in Japanese encephalitis virus infection

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) is one of the leading causes of acute encephalopathy with the highest mortality rate of 30-50%. The purpose of this study was to understand complex biological processes of host response during the progression of the disease. Virus was subcutaneously administered in mice and brain was used for whole genome expression profiling by cDNA microarray.</p> <p>Results</p> <p>The comparison between viral replication efficiency and disease progression confirms the active role of host response in immunopathology and disease severity. The histopathological analysis confirms the severe damage in the brain in a time dependent manner. Interestingly, the transcription profile reveals significant and differential expression of various pattern recognition receptors, chemotactic genes and the activation of inflammasome. The increased leukocyte infiltration and aggravated CNS inflammation may be the cause of disease severity.</p> <p>Conclusion</p> <p>This is the first report that provides a detailed picture of the host transcriptional response in a natural route of exposure and opens up new avenues for potential therapeutic and prophylactic strategies against Japanese encephalitis virus.</p

P2Y2 and P2Y6 receptor activation elicits intracellular calcium responses in human adipose-derived mesenchymal stromal cells

Adipose tissue contains self-renewing multipotent cells termed mesenchymal stromal cells. In situ, these cells serve to expand adipose tissue by adipogenesis, but their multipotency has gained interest for use in tissue regeneration. Little is known regarding the repertoire of receptors expressed by adipose-derived mesenchymal stromal cells (AD-MSCs). The purpose of this study was to undertake a comprehensive analysis of purinergic receptor expression. Mesenchymal stromal cells were isolated from human subcutaneous adipose tissue and confirmed by flow cytometry. The expression profile of purinergic receptors was determined by quantitative real-time PCR and immunocytochemistry. The molecular basis for adenine and uracil nucleotide-evoked intracellular calcium responses was determined using Fura-2 measurements. All the known subtypes of P2X and P2Y receptors, excluding P2X2, P2X3 and P2Y12 receptors, were detected at the mRNA and protein level. ATP, ADP and UTP elicited concentration-dependent calcium responses in mesenchymal cells (N = 7–9 donors), with a potency ranking ADP (EC50 1.3 ± 1.0 μM) > ATP (EC50 2.2 ± 1.1 μM) = UTP (3.2 ± 2.8 μM). Cells were unresponsive to UDP (< 30 μM) and UDP-glucose (< 30 μM). ATP responses were attenuated by selective P2Y2 receptor antagonism (AR-C118925XX; IC50 1.1 ± 0.8 μM, 73.0 ± 8.5% max inhibition; N = 7 donors), and UTP responses were abolished. ADP responses were attenuated by the selective P2Y6 receptor antagonist, MRS2587 (IC50 437 ± 133nM, 81.0 ± 8.4% max inhibition; N = 6 donors). These data demonstrate that adenine and uracil nucleotides elicit intracellular calcium responses in human AD-MSCs with a predominant role for P2Y2 and P2Y6 receptor activation. This study furthers understanding about how human adipose-derived mesenchymal stromal cells can respond to external signalling cues

CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis