The influence of large predators on the feeding ecology of two African mesocarnivores: the black-backed jackal and the brown hyaena

Interactions between apex and mesopredators and their impacts on prey populations have been well documented, while the influence of apex predators such as lions on carrion availability and the subsequent impacts at lower trophic levels are not fully understood. Here we assess dietary overlap between two sympatric carnivores (brown hyaena, Parahyaena brunnea, and black-backed jackal, Canis mesomelas) in neighbouring reserves with and without apex predators (lions, Panthera leo,and wild dog, Lycaon pictus). We investigate whether apex predators facilitate niche partitioning between mesocarnivores by creating additional scavenging opportunities through predatory activity. We found that brown hyaena density was higher in the area with apex predators, while black-backed jackal density was higher in the area without apex predators. Black-backed jackal scats contained broadly similar dietary items at both sites, while large mammal remains occurred significantly more frequently in brown hyaena scats collected inthe presence of apex predators. In the absence of apex predators there was a markedly higher degree of overlap between brown hyaena and jackal diets, suggesting increased levels of inter-specific competition. Our results suggest that apex predators potentially reduce levels of inter-specific competition for food between mesocarnivores by providing additional scavenging opportunities for specialist scavengers such as brown hyaena

A live vaccine against Neospora caninum abortions in cattle

CommentaryMichael P. Reichel, Dadín P. Moore, Andrew Hemphill, Luis M. Ortega-Mora, J.P. Dubey, John T. Elli

The gravitino coupling to broken gauge theories applied to the MSSM

We consider gravitino couplings in theories with broken gauge symmetries. In particular, we compute the single gravitino production cross section in W+ W- fusion processes. Despite recent claims to the contrary, we show that this process is always subdominant to gluon fusion processes in the high energy limit. The full calculation is performed numerically; however, we give analytic expressions for the cross section in the supersymmetric and electroweak limits. We also confirm these results with the use of the effective theory of goldstino interactions.Comment: 26 pages, 4 figure

Time to go global: a consultation on global health competencies for postgraduate doctors

BACKGROUND: Globalisation is having profound impacts on health and healthcare. We solicited the views of a wide range of stakeholders in order to develop core global health competencies for postgraduate doctors. METHODS: Published literature and existing curricula informed writing of seven global health competencies for consultation. A modified policy Delphi involved an online survey and face-to-face and telephone interviews over three rounds. RESULTS: Over 250 stakeholders participated, including doctors, other health professionals, policymakers and members of the public from all continents of the world. Participants indicated that global health competence is essential for postgraduate doctors and other health professionals. Concerns were expressed about overburdening curricula and identifying what is 'essential' for whom. Conflicting perspectives emerged about the importance and relevance of different global health topics. Five core competencies were developed: (1) diversity, human rights and ethics; (2) environmental, social and economic determinants of health; (3) global epidemiology; (4) global health governance; and (5) health systems and health professionals. CONCLUSIONS: Global health can bring important perspectives to postgraduate curricula, enhancing the ability of doctors to provide quality care. These global health competencies require tailoring to meet different trainees' needs and facilitate their incorporation into curricula. Healthcare and global health are ever-changing; therefore, the competencies will need to be regularly reviewed and updated

Fine Tuning in General Gauge Mediation

We study the fine-tuning problem in the context of general gauge mediation. Numerical analyses toward for relaxing fine-tuning are presented. We analyse the problem in typical three cases of the messenger scale, that is, GUT ($2\times10^{16}$ GeV), intermediate ($10^{10}$ GeV), and relatively low energy ($10^6$ GeV) scales. In each messenger scale, the parameter space reducing the degree of tuning as around 10% is found. Certain ratios among gluino mass, wino mass and soft scalar masses are favorable. It is shown that the favorable region becomes narrow as the messenger scale becomes lower, and tachyonic initial conditions of stop masses at the messenger scale are favored to relax the fine-tuning problem for the relatively low energy messenger scale. Our spectra would also be important from the viewpoint of the $\mu-B$ problem.Comment: 22 pages, 16 figures, comment adde

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end joining (NHEJ) pathway required for the repair of DNA double strand breaks. DNA-PKcs may be involved in breast cancer pathogenesis. Methods: We evaluated clinicopathological significance of DNA-PKcs protein expression in 1161 tumours and DNA-PKcs mRNA expression in 1950 tumours. We correlated DNA-PKcs to other markers of aggressive phenotypes, DNA repair, apoptosis and cell cycle regulation. Results: Low DNA-PKcs protein expression was associated with higher tumour grade, higher mitotic index, tumour de-differentiation and tumour type (ps<0.05). Absence of BRCA1, low XRCC1/SMUG1/APE1/Polβ were also more likely in low DNA-PKcs expressing tumours (ps<0.05). Low DNA-PKcs protein expression was significantly associated with worse breast cancer specific survival (BCCS) in univariate and multivariate analysis (ps<0.01). At the mRNA level, low DNA-PKcs was associated with PAM50.Her2 and PAM50.LumA molecular phenotypes (ps<0.01) and poor BCSS. In patients with ER positive tumours who received endocrine therapy, low DNA-PKcs (protein and mRNA) was associated with poor survival. In ER negative patients, low DNA-PKcs mRNA remains significantly associated with adverse outcome. Conclusions: Our study suggests that low DNA-PKcs expression may have prognostic and predictive significance in breast cancers

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. &lt;p/&gt;Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. &lt;p/&gt;Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Diagnostic dilemma: application of real-time PCR assays for the detection of Dientamoeba fragilis in medical and veterinary specimens.

BACKGROUND: Real-time PCR (qPCR) diagnostics developed for use in human clinical settings have been implemented to identify new animal hosts of the gastrointestinal protozoan Dientamoeba fragilis. The gut microbiome varies between species; unrecognised cross-reactivity could occur when applying these assays to new animal hosts. The use of qPCR diagnostics was assessed for the identification of new animal hosts of the gastrointestinal protozoan Dientamoeba fragilis. METHODS: Forty-nine cattle, 84 dogs, 39 cats and 254 humans were screened for D. fragilis using two qPCR assays: EasyScreen (Genetic Signatures) and a laboratory-based assay commonly used in Europe. The reliability of the identifications made by these assays were assessed using melt curve analysis of qPCR products, conventional PCR targeting the SSU rDNA sequencing and NGS amplicon sequencing of qPCR product. RESULTS: PCR products from the D. fragilis identified in cattle had a 9 °C cooler melt curve than when detected in humans. This melt curve discrepancy, indicative of cross-reactivity with an unknown organism, was investigated further. DNA sequencing determined that Simplicimonas sp. was the genera responsible for this cross-reactivity in cattle specimens. Dientamoeba fragilis was not detected in either dogs or cats. There was a discrepancy in the number of positive samples detected using the two qPCR assays when applied to human samples. The EasyScreen assay detected 24 positive samples; the laboratory-based assay detected an additional 34 positive samples. Of the discrepant samples, 5 returned sequence data for D. fragilis, and 29 were unsupported (false) positive samples. CONCLUSIONS: Analysis of the melt curve after the qPCR reaction is a valuable technique to help differentiate samples containing D. fragilis compared to cross-reactions with non-target organisms. The identification of new animal hosts requires further evidence from either microscopy or DNA sequencing to confirm the presence of D. fragilis. Additionally, to reduce the risk of false-positive results due to non-specific amplification, we recommend reducing the number of PCR cycles to less than 40. Based on these results, we consider the ramifications of this identified cross-reactivity to the known host species distribution of D. fragilis

On the nature of the fourth generation neutrino and its implications

We consider the neutrino sector of a Standard Model with four generations. While the three light neutrinos can obtain their masses from a variety of mechanisms with or without new neutral fermions, fourth-generation neutrinos need at least one new relatively light right-handed neutrino. If lepton number is not conserved this neutrino must have a Majorana mass term whose size depends on the underlying mechanism for lepton number violation. Majorana masses for the fourth generation neutrinos induce relative large two-loop contributions to the light neutrino masses which could be even larger than the cosmological bounds. This sets strong limits on the mass parameters and mixings of the fourth generation neutrinos.Comment: To be published. Few typos corrected, references update