Measuring between-farm variation in Culicoides (Diptera: Ceratopogonidae) density, the vectors of bluetongue virus

Culicoides midges are ubiquitous on farms in the UK, but little research has explored their abundance, an important determinant of disease risk. Models to explain and predict variation in their abundance are needed for effective targeting of control methods against bluetongue (BT) and other Culicoides-borne diseases. Midge abundances were estimated using light traps on 35 farms in north Wales. Culicoides catches were combined with remotely-sensed ecological correlates, and on-farm host and environmental data, within a general linear model. Local-scale variation in abundance exhibited an almost 500-fold difference between farms in maximum Obsoletus Group catches. The variance explained was consistently high for the BT vector species (81% for Obsoletus Group; 80% for Pulicaris Group, 73% for C. pulicaris, 74% for C. punctatus). The abundance of all vector species increased with the number of sheep on farms, but this relationship was missing from any of the non-vector models. At a large spatial scale, there is significant variation in Culicoides Obsoletus Group abundance, which undermines attempts to record their nationwide distribution in larger scale models. A prior survey should be undertaken for farms with high Culicoides catches within a sampling area and stability in catch size should be checked between seasons and years. (Résumé d'auteur

Modelling the spatial distribution of Culicoides biting midges at the local scale. [237]

Purpose: The Culicoides midge vectors of bluetongue (BT) are ubiquitous on farms in the UK, but little research has explored their spatial abundance, an important determinant of disease risk. Models to explain and predict variation in their abundance are needed for effective targeting of BT control methods. Although epidemiological models are commonplace at the national scale, no investigations have taken place at a finer spatial scale. Our aim is to identify determinants of midge abundance at a local 1 km scale. Methods: Midge abundances were estimated using light traps on 35 farms in north Wales. Culicoides catches were combined with remotely-sensed ecological correlates, and on-farm host and environmental data, within a general linear model. Drivers of local scale variation were determined at the 1 km resolution. Results: Local-scale variation in Obsoletus Group abundance exhibited an almost 500-fold difference (74 to 33,720) between farms, but the Obsoletus Group model explained 81% of this variance. The variance explained was consistently high for the Pulicaris Group, C. pulicaris and C. punctatus (80%, 73%, and 74%), the other possible BTV vector species in the UK. The abundance of all vector species increased with the number of sheep on farms, but this relationship was missing from any of the non-vector models. Performance of the non-vector models was also high (65-87% variance explained), but species differed in their associations with satellite variables. Conclusions: At a large spatial scale, there is significant variation in Culicoides Obsoletus Group abundance, undermining attempts to record their nationwide distribution in larger scale models, which have historically explained the abundance of these vectors poorly. Satellite data can be used to explain a high proportion of this variation and may produce effective predictive models of disease vector abundance. Relevance: This work highlights how novel local-scale modelling of disease vectors can explain a large degree of spatial variation that national-scale models fail to explain. This should be of note to policy makers when deciding upon guidelines for entomological surveys before, during and after disease outbreaks. (Texte intégral

Spontaneous Transformation of Murine Oviductal Epithelial Cells: A Model System to Investigate the Onset of Fallopian-Derived Tumors

High-grade serous carcinoma (HGSC) is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs) are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described. Apart from a subpopulation of genetically predisposed women, most women develop ovarian cancer spontaneously, which is associated with aging and lifetime ovulations. A murine oviductal cell line (MOELOW) was developed and continuously passaged in culture to mimic cellular aging (MOEHIGH). The MOEHIGH cellular model exhibited a loss of acetylated tubulin consistent with an outgrowth of secretory epithelial cells in culture. MOEHIGH cells proliferated significantly faster than MOELOW, and the MOEHIGH cells produced more 2D foci and 3D soft agar colonies as compared to MOELOW. MOEHIGH were xenografted into athymic female nude mice both in the subcutaneous and the intraperiteonal compartments. Only the subcutaneous grafts formed tumors that were negative for cytokeratin, but positive for oviductal markers such as oviductal glycoprotein 1 and Pax8. These tumors were considered to be poorly differentiated carcinoma. The differential molecular profiles between MOEHIGH and MOELOW were determined using RNA-Seq and confirmed by protein expression to uncover pathways important in transformation, like the p53 pathway, the FOXM1 pathway, WNT signaling, and splicing. MOEHIGH had enhanced protein expression of c-myc, Cyclin E, p53 and FOXM1 with reduced expression of p21. MOEHIGH were also less sensitive to cisplatin and DMBA, which induce lesions typically repaired by base-excision repair. A model of spontaneous tumorogenesis was generated starting with normal oviductal cells. Their transition to cancer involved alterations in pathways associated with high-grade serous cancer in humans

Residents’ Perceptions of Tourism Development in Appalachian Forest Heritage Area

The Appalachian Forest Heritage Area (AFHA) is made up of 18 counties which are located in the central Appalachia, a region rich in natural, historic and heritage resources with great potentials for tourism development. In order to know more about tourism development in the area, a study to understand AFHA community residents’ perceptions of tourism opportunities, issues, and potentials was conducted with funding from West Virginia University Extension Service. Results indicated that participants considered people, natural resources, and historical/heritage resources as the most valued assets that their communities can use for tourism development. They were also very positive about the environmental, social, economic, impacts of tourism on their communities. The study recommended that top priorities should be placed on strengthening community leadership; increasing financial investment; and promoting marketing for tourism development in the AFHA communities

A dose ranging trial to optimize the dose of Rifampin in the treatment of tuberculosis

The study was funded by the EDCTP (European & Developing Countries Clinical Trials Partnership), NACCAP (Netherlands-African partnership for Capacity development and Clinical interventions Against Poverty-related diseases) and the Bill & Melinda Gates Foundation.Rationale: Rifampin at a dose of 10 mg/kg was introduced in 1971 based on pharmacokinetic, toxicity and cost considerations. Available data in mice and humans showed that an increase in dose may shorten the duration of tuberculosis treatment. Objectives: To evaluate the safety and tolerability, the pharmacokinetics and the extended early bactericidal activity of increasing doses of rifampin. Methods: Patients with drug-susceptible tuberculosis were enrolled into a control group of 8 patients receiving the standard dose of 10 mg/kg rifampin, followed by consecutive experimental groups with 15 patients each receiving rifampin 20 mg/kg, 25 mg/kg, 30 mg/kg and 35 mg/kg, respectively, for 14 days. In all patients isoniazid, pyrazinamide and ethambutol were added in standard doses for the second 7 days of treatment. Safety, pharmacokinetics of rifampin, and fall in bacterial load were assessed. Measurements and Main Results: Grade 1 and 2 adverse events were equally distributed between the five dose groups; there were 5 grade 3 events of which 1 was a possibly related hepatotoxicity. Areas under the time-concentration curves and peak serum concentrations of rifampin showed a more than proportional increase with dose. The daily fall in bacterial load over 14 days was 0.176, 0.168, 0.167, 0.265, and 0.261 log10CFU/ml sputum in the 10, 20, 25, 30 and 35 mg/kg groups respectively. Conclusions: Two weeks of rifampin up to 35 mg/kg was safe and well tolerated. There was a non-linear increase in exposure to rifampin without an apparent ceiling effect and a greater estimated fall in bacterial load in the higher dosing groups. Clinical trial registration available at www.clinicaltrials.gove, ID NCT01392911.PostprintPeer reviewe

Long-Range Correlations in Rectal Temperature Fluctuations of Healthy Infants during Maturation

BACKGROUND. Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (Trec) patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS. We measured Trec fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, a using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that Trec fluctuations exhibit fractal long-range correlations with a mean (SD) a of 1.51 (0.11), indicating that Trec is regulated in a highly correlated and hence deterministic manner. A significant increase in a with age from 1.42 (0.07) at 4 weeks to 1.58 (0.04) at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. a was not associated with mean room temperature or influenced by immunization CONCLUSIONS. This study shows that the quantification of long-range correlations using a derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time Trec pattern in young infants, reflective of maturation of the autonomic system. Detrended fluctuation analysis may prove useful for characterizing thermoregulation in premature and other infants at risk for life-threatening events.British Society of the Protection of Infants Life; Swiss National Science Foundation (32-68025.02); ERS Long-Term Research Fellowship; National Science Foundation (BES 0114538); Swiss National Science Foundation (3200-B0-112099); Swiss Federal Office of Public Health (Anti-Tobacco Fund

Segregated neural explants exhibit co-oriented, asymmetric, neurite outgrowth

Explants of embryonic chick sympathetic and sensory ganglia were found to exhibit asymmetric radial outgrowth of neurites under standard culture conditions with or without exogenous Nerve Growth Factor [NGF]. Opposing sides of an explant exhibited: a) differences in neurite length and, b) differences in neurite morphology. Strikingly, this asymmetry exhibited co-orientation among segregated, neighboring explants. The underlying mechanism(s) of the asymmetry and its co-orientation are not known but appear to depend on cell clustering because dissociated sympathetic neurons do not exhibit co-orientation whereas re-aggregated clusters of cells do. This emergent behavior may be similar to the community effect described in other cell types. If a similar phenomenon exists in the embryo, or in maturity, it may contribute to the establishment of proper orientation of neurite outgrowth during development and/or injury-induced neuronal plasticity

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Surface Inorganic Iodine Speciation in the Indian and Southern Oceans From 12°N to 70°S

Marine iodine speciation has emerged as a potential tracer of primary productivity, sedimentary inputs, and ocean oxygenation. The reaction of iodide with ozone at the sea surface has also been identified as the largest deposition sink for tropospheric ozone and the dominant source of iodine to the atmosphere. Accurate incorporation of these processes into atmospheric models requires improved understanding of iodide concentrations at the air-sea interface. Observations of sea surface iodide are relatively sparse and are particularly lacking in the Indian Ocean basin. Here we examine 127 new sea surface (≤10 m depth) iodide and iodate observations made during three cruises in the Indian Ocean and the Indian sector of the Southern Ocean. The observations span latitudes from ∼12°N to ∼70°S, and include three distinct hydrographic regimes: the South Indian subtropical gyre, the Southern Ocean and the northern Indian Ocean including the southern Bay of Bengal. Concentrations and spatial distribution of sea surface iodide follow the same general trends as in other ocean basins, with iodide concentrations tending to decrease with increasing latitude (and decreasing sea surface temperature). However, the gradient of this relationship was steeper in subtropical waters of the Indian Ocean than in the Atlantic or Pacific, suggesting that it might not be accurately represented by widely used parameterizations based on sea surface temperature. This difference in gradients between basins may arise from differences in phytoplankton community composition and/or iodide production rates. Iodide concentrations in the tropical northern Indian Ocean were higher and more variable than elsewhere. Two extremely high iodide concentrations (1241 and 949 nM) were encountered in the Bay of Bengal and are thought to be associated with sedimentary inputs under low oxygen conditions. Excluding these outliers, sea surface iodide concentrations ranged from 20 to 250 nM, with a median of 61 nM. Controls on sea surface iodide concentrations in the Indian Ocean were investigated using a state-of-the-art iodine cycling model. Multiple interacting factors were found to drive the iodide distribution. Dilution via vertical mixing and mixed layer depth shoaling are key controls, and both also modulate the impact of biogeochemical iodide formation and loss processes