Density Dependence of Transport Coefficients from Holographic Hydrodynamics

We study the transport coefficients of Quark-Gluon-Plasma in finite temperature and finite baryon density. We use AdS/QCD of charged AdS black hole background with bulk-filling branes identifying the U(1) charge as the baryon number. We calculate the diffusion constant, the shear viscosity and the thermal conductivity to plot their density and temperature dependences. Hydrodynamic relations between those are shown to hold exactly. The diffusion constant and the shear viscosity are decreasing as a function of density for fixed total energy. For fixed temperature, the fluid becomes less diffusible and more viscous for larger baryon density.Comment: LaTeX, 1+33 pages, 6 figures, references adde

Clinical update on the use of biomarkers of airway inflammation in the management of asthma

Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and create personalized treatment regimes. Asthma is a heterogeneous disease with several different phenotypes, generally triggered by multiple gene-environment interactions. Pulmonary function tests are most often used objectively to confirm the diagnosis. However, airflow obstruction can be variable and thus missed using spirometry. Furthermore, lung function measurements may not reflect the precise underlying pathological processes responsible for different phenotypes. Inhaled corticosteroids and β2-agonists have been the mainstay of asthma therapy for over 30 years, but the heterogeneity of the disease means not all asthmatics respond to the same treatment. High costs and undesired side effects of drugs also drive the need for better targeted treatment of asthma. Biomarkers have the potential to indicate an individual’s disease phenotype and thereby guide clinicians in their decisions regarding treatment. This review focuses on biomarkers of airway inflammation which may help us to identify, monitor, and guide treatment of asthmatics. We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine. We discuss the inherent limitations and benefits of using biomarkers in a heterogeneous disease such as asthma. We also discuss how we may modify our study designs to improve the identification and potential use of potential biomarkers in asthma

Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, therby promoting Th2- and Tr1-biased T-cell immunity

Although many advantageous roles of cisplatin (cis-diamminedichloroplatinum (II), CDDP) have been reported in cancer therapy, the immunomodulatory roles of cisplatin in the phenotypic and functional alterations of dendritic cells (DCs) are poorly understood. Here, we investigated the effect of cisplatin on the functionality of DCs and the changes in signaling pathways activated upon toll-like receptor (TLR) stimulation. Cisplatin-treated DCs down-regulated the expression of cell surface molecules (CD80, CD86, MHC class I and II) and up-regulated endocytic capacity in a dose-dependent manner. Upon stimulation with various TLR agonists, cisplatintreated DCs showed markedly increased IL-10 production through activation of the p38 MAPK and NF-κB signaling pathways without altering the levels of TNF-α and IL- 12p70, indicating the cisplatin-mediated induction of tolerogenic DCs. This effect was dependent on the production of IL-10 from DCs, as neither DCs isolated from IL-10- /- mice nor IL-10-neutralized DCs generated tolerogenic DCs. Interestingly, DCs that were co-treated with cisplatin and lipopolysaccharide (LPS) exhibited a decreased immunostimulatory capacity for inducing the proliferation of Th1- and Th17-type T cells; instead, these DCs contributed to Th2-type T cell immunity. Furthermore, in vitro and in vivo investigations revealed a unique T cell population, IL-10-producing CD3+CD4+LAG-3+CD49b+CD25-Foxp3- Tr1 cells, that was significantly increased without altering the Foxp3+ regulatory T cell population. Taken together, our results suggest that cisplatin induces immune-suppressive tolerogenic DCs in TLR agonistinduced inflammatory conditions via abundant IL-10 production, thereby skewing Th cell differentiation towards Th2 and Tr1 cells. This relationship may provide cancer cells with an opportunity to evade the immune system.1231sciescopu

Sound Modes in Holographic Hydrodynamics for Charged AdS Black Hole

In the previous paper we studied the transport coefficients of Quark-Gluon Plasma in finite temperature and finite density in vector and tensor modes. In this paper, we extend it to the scalar modes. We work out the decoupling problem and hydrodynamic analysis for the sound mode in charged AdS black hole and calculate the sound velocity, the charge susceptibility and the electrical conductivity. We find that Einstein relation among the conductivity, the diffusion constant and the susceptibility holds exactly.Comment: 1+33 pages, 4 figures, LaTeX; references added, improved section 4.

Service and treatment engagement of people with very late-onset schizophrenia-like psychosis

AIMS AND METHOD: Electronic patient records were used to investigate the level of engagement and treatment that patients with very late-onset schizophrenia-like psychosis (VLOSLP) had with mental health services. RESULTS: Of 131 patients assessed and diagnosed, 63 (48%) were taking antipsychotic treatment at 3 months, 46 (35%) at 6 months and 36 (27%) at 12 months. At discharge from mental health services, 54% of patients had failed to engage with services or became lost to follow-up, 18% had engaged with services but were not taking antipsychotic medication and only 28% were taking treatment. CLINICAL IMPLICATIONS: Results showed that less than half of the patients with VLOSLP were commenced on antipsychotic treatment and less than a third remained on treatment at 1 year or at point of discharge. This highlights the need for services to consider being more assertive in taking potentially effective treatment to this patient group. DECLARATION OF INTERESTS: R.H. is chief investigator and S.J.R. is a co-investigator on the NIHR-funded randomised clinical trial of Antipsychotic Treatment of very LAte-onset Schizophrenia-like psychosis (ATLAS)

On nonsupersymmetric \BC^4/\BZ_N, tachyons, terminal singularities and flips

We investigate nonsupersymmetric \BC^4/\BZ_N orbifold singularities using their description in terms of the string worldsheet conformal field theory and its close relation with the toric geometry description of these singularities and their possible resolutions. Analytic and numerical study strongly suggest the absence of nonsupersymmetric Type II terminal singularities (i.e. with no marginal or relevant blowup modes) so that there are always moduli or closed string tachyons that give rise to resolutions of these singularities, although supersymmetric and Type 0 terminal singularities do exist. Using gauged linear sigma models, we analyze the phase structure of these singularities, which often involves 4-dimensional flip transitions, occurring between resolution endpoints of distinct topology. We then discuss 4-dim analogs of unstable conifold-like singularities that exhibit flips, in particular their Type II GSO projection and the phase structure. We also briefly discuss aspects of M2-branes stacked at such singularities and nonsupersymmetric AdS_4\times S^7/\BZ_N backgrounds.Comment: Latex, 43pgs incl. appendices, 2 eps figs, v2. minor clarifications added, to appear in JHE

Systemic inflammation in chronic obstructive pulmonary disease: a population-based study

<p>Abstract</p> <p>Background</p> <p>Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution. The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.</p> <p>Methods</p> <p>This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age). Subjects with any other condition associated with an inflammatory process were excluded. COPD was defined as a post-bronchodilator FEV₁/FVC < 0.70. The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication. Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests. Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.</p> <p>Results</p> <p>We compared 324 COPD patients and 110 reference subjects. After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs. 0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs. 10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs. 3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs. 1.36 ± 0.02 log nmol/l; p = 0.048) than controls. In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.</p> <p>Conclusions</p> <p>Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects.</p

Relationship between cyclooxygenase 8473T>C polymorphism and the risk of lung cancer: a case-control study

BACKGROUND: Cyclooxygenase-2 (COX-2) plays an important role in the development of lung cancer. DNA sequence variations in the COX-2 gene may lead to altered COX-2 production and/or activity, and so they cause inter-individual differences in the susceptibility to lung cancer. To test this hypothesis, we investigated the association between the 8473T>C polymorphism in the 3'-untranslated region of the COX-2 gene and the risk of lung cancer in a Korean population. METHODS: The COX-2 genotypes were determined using PCR-based primer-introduced restriction analysis in 582 lung cancer patients and in 582 healthy controls that were frequency-matched for age and gender. RESULTS: The distribution of the COX-2 8473T>C genotypes was not significantly different between the overall lung cancer cases and the controls. However, when the cases were categorized by the tumor histology, the combined 8473 TC + CC genotype was associated with a significantly decreased risk of adenocarcinoma as compared with the 8473 TT genotype (adjusted OR = 0.64; 95% CI = 0.46–0.90, P = 0.01). On the stratification analysis, the protective effect of the combined 8473 TC + CC genotype against adenocarcinoma was statistically significant in the males, older individuals and ever-smokers (adjusted OR = 0.59; 95% CI = 0.39–0.91, P = 0.02; adjusted OR = 0.55; 95% CI = 0.33–0.93, P = 0.03; and adjusted OR = 0.57; 95% CI = 0.37–0.87, P = 0.01, respectively). CONCLUSION: These findings suggest that the COX-2 8473T>C polymorphism could be used as a marker for the genetic susceptibility to adenocarcinoma of the lung

Outcome measures in chronic obstructive pulmonary disease (COPD): strengths and limitations

Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires. The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality. Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology. Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD

Combining scores from different patient reported outcome measures in meta-analyses: when is it justified?

BACKGROUND: Combining outcomes and the use of standardized effect measures such as effect size and standardized response mean across instruments allows more comprehensive meta-analyses and should avoid selection bias. However, such analysis ideally requires that the instruments correlate strongly and that the underlying assumption of similar responsiveness is fulfilled. The aim of the study was to assess the correlation between two widely used health-related quality of life instruments for patients with chronic obstructive pulmonary disease and to compare the instruments' responsiveness on a study level. METHODS: We systematically identified all longitudinal studies that used both the Chronic Respiratory Questionnaire (CRQ) and the St. George's Respiratory Questionnaire (SGRQ) through electronic searches of MEDLINE, EMBASE, CENTRAL and PubMed. We assessed the correlation between CRQ (scale 1 – 7) and SGRQ (scale 1 – 100) change scores and compared responsiveness of the two instruments by comparing standardized response means (change scores divided by their standard deviation). RESULTS: We identified 15 studies with 23 patient groups. CRQ change scores ranged from -0.19 to 1.87 (median 0.35, IQR 0.14–0.68) and from -16.00 to 3.00 (median -3.00, IQR -4.73–0.25) for SGRQ change scores. The correlation between CRQ and SGRQ change scores was 0.88. Standardized response means of the CRQ (median 0.51, IQR 0.19–0.98) were significantly higher (p < 0.001) than for the SGRQ (median 0.26, IQR -0.03–0.40). CONCLUSION: Investigators should be cautious about pooling the results from different instruments in meta-analysis even if they appear to measure similar constructs. Despite high correlation in changes scores, responsiveness of instruments may differ substantially and could lead to important between-study heterogeneity and biased meta-analyses