Evaluating the potential for the environmentally sustainable control of foot and mouth disease in Sub-Saharan Africa

Strategies to control transboundary diseases have in the past generated unintended negative consequences for both the environment and local human populations. Integrating perspectives from across disciplines, including livestock, veterinary and conservation sectors, is necessary for identifying disease control strategies that optimise environmental goods and services at the wildlife-livestock interface. Prompted by the recent development of a global strategy for the control and elimination of foot-and-mouth disease (FMD), this paper seeks insight into the consequences of, and rational options for potential FMD control measures in relation to environmental, conservation and human poverty considerations in Africa. We suggest a more environmentally nuanced process of FMD control that safe-guards the integrity of wild populations and the ecosystem dynamics on which human livelihoods depend while simultaneously improving socio-economic conditions of rural people. In particular, we outline five major issues that need to be considered: 1) improved understanding of the different FMD viral strains and how they circulate between domestic and wildlife populations; 2) an appreciation for the economic value of wildlife for many African countries whose presence might preclude the country from ever achieving an FMD-free status; 3) exploring ways in which livestock production can be improved without compromising wildlife such as implementing commodity-based trading schemes; 4) introducing a participatory approach involving local farmers and the national veterinary services in the control of FMD; and 5) finally the possibility that transfrontier conservation might offer new hope of integrating decision-making at the wildlife-livestock interface

Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms

Local recurrence after surgery for non–small cell lung cancer: A recursive partitioning analysis of multi-institutional data

OBJECTIVE: To define subgroups at high risk of local recurrence (LR) after surgery for non-small cell lung cancer using a recursive partitioning analysis (RPA). METHODS: This Institutional Review Board-approved study included patients who underwent upfront surgery for I-IIIA non-small cell lung cancer at Duke Cancer Institute (primary set) or at other participating institutions (validation set). The 2 data sets were analyzed separately and identically. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered an LR. Recursive partitioning was used to build regression trees for the prediction of local recurrence-free survival (LRFS) from standard clinical and pathological factors. LRFS distributions were estimated with the Kaplan-Meier method. RESULTS: The 1411 patients in the primary set had a 5-year LRFS rate of 77% (95% confidence interval [CI], 0.74-0.81), and the 889 patients in the validation set had a 5-year LRFS rate of 76% (95% CI, 0.72-0.80). The RPA of the primary data set identified 3 terminal nodes based on stage and histology. These nodes and their 5-year LRFS rates were as follows: (1) stage I/adenocarcinoma, 87% (95% CI, 0.83-0.90); (2) stage I/squamous or large cell, 72% (95% CI, 0.65-0.79); and (3) stage II-IIIA, 62% (95% CI, 0.55-0.69). The validation RPA identified 3 terminal nodes based on lymphovascular invasion (LVI) and stage: (1) no LVI/stage IA, 82% (95% CI, 0.76-0.88); (2) no LVI/stage IB-IIIA, 73% (95% CI, 0.69-0.80); and (3) LVI, 58% (95% CI, 0.47-0.69). CONCLUSIONS: The risk of LR was similar in the primary and validation patient data sets. There was discordance between the 2 data sets regarding the clinical factors that best segregate patients into risk groups

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs

PCA3 molecular urine assay for prostate cancer: association with pathologic features and impact of collection protocols

IntroductionPCA3 is a non-coding mRNA molecule that is overexpressed in prostate cancer. The purpose of this study is to evaluate the utility of the PCA3 molecular urine test scores to predict adverse pathologic features and catheterized specimen collection.MethodsHundred men with clinically localized prostate cancer scheduled to undergo robotic prostatectomy were enrolled in the study following a standard consent process. The study protocol consisted of providing four urine samples. Voided urine obtained following digital rectal examination (DRE) pre-operatively (Vl), catheterized urine without DRE (V2), and l0-day and 6-week postoperative voided (V3 and V4) urine samples were collected and analyzed. These four urine specimens underwent target capture, transcription-mediated amplification, and hybridization in order to quantify both PCA3 and PSA mRNA. The PCA3 score was calculated as the ratio of PCA3 to PSA.ResultsInformative rates (sufficient mRNA for analysis) for VI, V2, V3 and V4 were 91, 85, 0 and 2%, respectively. There was no significant associations with pathological stage, Gleason score >6. Higher PCA3 scores at V1 correlated with increased risk for perineural invasion (P = 0.0479).ConclusionsInformative PCA3 scores can be obtained from post-DRE voided urine as well as catheterized urine without a DRE. The PCA3 test does not seem to predict adverse pathologic features, though, may have an association with perineural invasion. The ability of PCA3 score to predict clinical outcome remains to be determined

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Spirituality and end-of-life care in disadvantaged men dying of prostate cancer

Despite the positive influence of spiritual coping on the acceptance of a cancer diagnosis, higher spirituality is associated with receipt of more high intensity care at the end of life. The purpose of our study was to assess the association between spirituality and type of end-of-life care received by disadvantaged men with prostate cancer. We studied low-income, uninsured men in IMPACT, a state-funded public assistance program, who had died since its inception in 2001. Of the 60 men who died, we included the 35 who completed a spirituality questionnaire at program enrollment. We abstracted sociodemographic and clinical information as well as treatment within IMPACT, including zolendroic acid, chemotherapy, hospice use, and palliative radiation therapy. We measured spirituality with the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being questionnaire (FACIT-Sp) and compared end-of-life care received between subjects with low and high FACIT-Sp scores using chi-squared analyses. A higher proportion of men with high (33%) versus low (13%) spirituality scores enrolled in hospice, although our analysis was not adequately powered to demonstrate statistical significance. Likewise, we saw a trend toward increased receipt of palliative radiation among those with higher spirituality (37% vs. 25%, P = 0.69). The differences in end-of-life care received among those with low and high spirituality varied little by the FACIT-Sp peace and faith subscales. End-of-life care was similar between men with lower and higher spirituality. Men with higher spirituality trended toward greater hospice use, suggesting that they redirected the focus of their care from curative to palliative goals

Unmanned aircraft systems as a new source of disturbance for wildlife: A systematic review.

The use of small Unmanned Aircraft Systems (UAS; also known as "drones") for professional and personal-leisure use is increasing enormously. UAS operate at low altitudes (<500 m) and in any terrain, thus they are susceptible to interact with local fauna, generating a new type of anthropogenic disturbance that has not been systematically evaluated. To address this gap, we performed a review of the existent literature about animals' responses to UAS flights and conducted a pooled analysis of the data to determine the probability and intensity of the disturbance, and to identify the factors influencing animals' reactions towards the small aircraft. We found that wildlife reactions depended on both the UAS attributes (flight pattern, engine type and size of aircraft) and the characteristics of animals themselves (type of animal, life-history stage and level of aggregation). Target-oriented flight patterns, larger UAS sizes, and fuel-powered (noisier) engines evoked the strongest reactions in wildlife. Animals during the non-breeding period and in large groups were more likely to show behavioral reactions to UAS, and birds are more prone to react than other taxa. We discuss the implications of these results in the context of wildlife disturbance and suggest guidelines for conservationists, users and manufacturers to minimize the impact of UAS. In addition, we propose that the legal framework needs to be adapted so that appropriate actions can be undertaken when wildlife is negatively affected by these emergent practices