Dark Radiation and Dark Matter in Large Volume Compactifications

We argue that dark radiation is naturally generated from the decay of the overall volume modulus in the LARGE volume scenario. We consider both sequestered and non-sequestered cases, and find that the axionic superpartner of the modulus is produced by the modulus decay and it can account for the dark radiation suggested by observations, while the modulus decay through the Giudice-Masiero term gives the dominant contribution to the total decay rate. In the sequestered case, the lightest supersymmetric particles produced by the modulus decay can naturally account for the observed dark matter density. In the non-sequestered case, on the other hand, the supersymmetric particles are not produced by the modulus decay, since the soft masses are of order the heavy gravitino mass. The QCD axion will then be a plausible dark matter candidate.Comment: 27 pages, 4 figures; version 3: version published in JHE

Massive Abelian Gauge Symmetries and Fluxes in F-theory

F-theory compactified on a Calabi-Yau fourfold naturally describes non-Abelian gauge symmetries through the singularity structure of the elliptic fibration. In contrast Abelian symmetries are more difficult to study because of their inherently global nature. We argue that in general F-theory compactifications there are massive Abelian symmetries, such as the uplift of the Abelian part of the U(N) gauge group on D7-branes, that arise from non-Kahler resolutions of the dual M-theory setup. The four-dimensional F-theory vacuum with vanishing expectation values for the gauge fields corresponds to the Calabi-Yau limit. We propose that fluxes that are turned on along these U(1)s are uplifted to non-harmonic four-form fluxes. We derive the effective four-dimensional gauged supergravity resulting from F-theory compactifications in the presence of the Abelian gauge factors including the effects of possible fluxes on the gauging, tadpoles and matter spectrum.Comment: 49 page

The Conformal Sector of F-theory GUTs

D3-brane probes of exceptional Yukawa points in F-theory GUTs are natural hidden sectors for particle phenomenology. We find that coupling the probe to the MSSM yields a new class of N = 1 conformal fixed points with computable infrared R-charges. Quite surprisingly, we find that the MSSM only weakly mixes with the strongly coupled sector in the sense that the MSSM fields pick up small exactly computable anomalous dimensions. Additionally, we find that although the states of the probe sector transform as complete GUT multiplets, their coupling to Standard Model fields leads to a calculable threshold correction to the running of the visible sector gauge couplings which improves precision unification. We also briefly consider scenarios in which SUSY is broken in the hidden sector. This leads to a gauge mediated spectrum for the gauginos and first two superpartner generations, with additional contributions to the third generation superpartners and Higgs sector.Comment: v2: 51 pages, 2 figures, remark added, typos correcte

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

<p>Abstract</p> <p>Background</p> <p>Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters.</p> <p>Methods</p> <p>In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05.</p> <p>Results</p> <p>Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour.</p> <p>Conclusion</p> <p>Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss exceeded 5% there was a significantly reduced resection rate to detect, but the changes were significantly more substantial if weight loss was 10% or more. We propose that a weight loss of 10% be defined as significant in pancreatic cancer.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genomic Targets of Brachyury (T) in Differentiating Mouse Embryonic Stem Cells

The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species

Evaluation of DNA ploidy in relation with established prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Most patients with ductal pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to evaluate the prognostic significance of DNA ploidy in relation with established clinical and laboratory variables in such patients.</p> <p>Methods</p> <p>Two hundred and twenty six patients were studied retrospectively. Twenty two potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined.</p> <p>Results</p> <p>Mean survival time was 38.41 weeks (95% c.i.: 33.17–43.65), median survival 27.00 weeks (95% c.i.: 23.18–30.82). On multivariate analysis, 10 factors had an independent effect on survival: performance status, local extension of tumor, distant metastases, ploidy score, anemia under epoetin therapy, weight loss, pain, steatorrhoea, CEA, and palliative surgery and chemotherapy. Patients managed with palliative surgery and chemotherapy had 6.7 times lower probability of death in comparison with patients without any treatment. Patients with ploidy score > 3.6 had 5.0 times higher probability of death in comparison with patients with ploidy score < 2.2 and these with ploidy score 2.2–3.6 had 6.3 times higher probability of death in comparison with patients with ploidy score < 2.2.</p> <p>Conclusion</p> <p>According to the significance of the examined factor, survival was improved mainly by the combination of surgery and chemotherapy, and the presence of low DNA ploidy score.</p

Snake Cathelicidin from Bungarus fasciatus Is a Potent Peptide Antibiotics

Background: Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules of innate immunity, which are firstly found in mammalians. Recently, several cathelicidins have also been found from chickens and fishes. No cathelicidins from other non-mammalian vertebrates have been reported. Principal Findings: In this work, a cathelicidin-like antimicrobial peptide named cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and its cDNA sequence was cloned from the cDNA library, which confirm the presence of cathelicidin in reptiles. As other cathelicidins, the precursor of cathelicidin-BF has cathelin-like domain at the N terminus and carry the mature cathelicidin-BF at the C terminus, but it has an atypical acidic fragment insertion between the cathelin-like domain and the C-terminus. The acidic fragment is similar to acidic domains of amphibian antimicrobial precursors. Phylogenetic analysis revealed that the snake cathelicidin had the nearest evolution relationship with platypus cathelicidin. The secondary structure of cathelicidin-BF investigated by CD and NMR spectroscopy in the presence of the helicogenic solvent TFE is an amphipathic α-helical conformation as many other cathelicidins. The antimicrobial activities of cathelicidin BF against forty strains of microorganisms were tested. Cathelicidin-BF efficiently killed bacteria and some fungal species including clinically isolated drug-resistance microorganisms. It was especially active against Gram-negative bacteria. Furthermore, it could exert antimicrobial activity against some saprophytic fungus. No hemolytic and cytotoxic activity was observed at the dose of up to 400 µg/ml. Cathelicidin-BF could exist stably in the mice plasma for at least 2.5 hours. Conclusion: Discovery of snake cathelicidin with atypical structural and functional characterization offers new insights on the evolution of cathelicidins. Potent, broad spectrum, salt-independent antimicrobial activities make cathelicidin-BF an excellent candidate for clinical or agricultural antibiotics