Ewens measures on compact groups and hypergeometric kernels

On unitary compact groups the decomposition of a generic element into product of reflections induces a decomposition of the characteristic polynomial into a product of factors. When the group is equipped with the Haar probability measure, these factors become independent random variables with explicit distributions. Beyond the known results on the orthogonal and unitary groups (O(n) and U(n)), we treat the symplectic case. In U(n), this induces a family of probability changes analogous to the biassing in the Ewens sampling formula known for the symmetric group. Then we study the spectral properties of these measures, connected to the pure Fisher-Hartvig symbol on the unit circle. The associated orthogonal polynomials give rise, as $n$ tends to infinity to a limit kernel at the singularity.Comment: New version of the previous paper "Hua-Pickrell measures on general compact groups". The article has been completely re-written (the presentation has changed and some proofs have been simplified). New references added

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Appropriate disclosure of a diagnosis of dementia : identifying the key behaviours of 'best practice'

Background: Despite growing evidence that many people with dementia want to know their diagnosis, there is wide variation in attitudes of professionals towards disclosure. The disclosure of the diagnosis of dementia is increasingly recognised as being a process rather than a one-off behaviour. However, the different behaviours that contribute to this process have not been comprehensively defined. No intervention studies to improve diagnostic disclosure in dementia have been reported to date. As part of a larger study to develop an intervention to promote appropriate disclosure, we sought to identify important disclosure behaviours and explore whether supplementing a literature review with other methods would result in the identification of new behaviours. Methods: To identify a comprehensive list of behaviours in disclosure we conducted a literature review, interviewed people with dementia and informal carers, and used a consensus process involving health and social care professionals. Content analysis of the full list of behaviours was carried out. Results: Interviews were conducted with four people with dementia and six informal carers. Eight health and social care professionals took part in the consensus panel. From the interviews, consensus panel and literature review 220 behaviours were elicited, with 109 behaviours over-lapping. The interviews and consensus panel elicited 27 behaviours supplementary to the review. Those from the interviews appeared to be self-evident but highlighted deficiencies in current practice and from the panel focused largely on balancing the needs of people with dementia and family members. Behaviours were grouped into eight categories: preparing for disclosure; integrating family members; exploring the patient's perspective; disclosing the diagnosis; responding to patient reactions; focusing on quality of life and well-being; planning for the future; and communicating effectively. Conclusion: This exercise has highlighted the complexity of the process of disclosing a diagnosis of dementia in an appropriate manner. It confirms that many of the behaviours identified in the literature (often based on professional opinion rather than empirical evidence) also resonate with people with dementia and informal carers. The presence of contradictory behaviours emphasises the need to tailor the process of disclosure to individual patients and carers. Our combined methods may be relevant to other efforts to identify and define complex clinical practices for further study.This project is funded by UK Medical Research Council, Grant reference number G0300999

The recording and characteristics of pulmonary rehabilitation in patients with COPD using The Health Information Network (THIN) primary care database

Pulmonary rehabilitation is recommended for patients with COPD to improve physical function, breathlessness and quality of life. Using The Health Information Network (THIN) primary care database in UK, we compared the demographic and clinical parameters of patients with COPD in relation to coding of pulmonary rehabilitation, and to investigate whether there is a survival benefit from pulmonary rehabilitation. We identified patients with COPD, diagnosed from 2004 and extracted information on demographics, pulmonary rehabilitation and clinical parameters using the relevant Read codes. Thirty six thousand one hundred and eighty nine patients diagnosed with COPD were included with a mean (SD) age of 67 (11) years, 53% were male and only 9.8% had a code related to either being assessed, referred, or completing pulmonary rehabilitation ever. Younger age at diagnosis, better socioeconomic status, worse dyspnoea score, current smoking, and higher comorbidities level are more likely to have a record of pulmonary rehabilitation. Of those with a recorded MRC of 3 or worse, only 2057 (21%) had a code of pulmonary rehabilitation. Survival analysis revealed that patients with coding for pulmonary rehabilitation were 22% (95% CI 0.69–0.88) less likely to die than those who had no coding. In UK THIN records, a substantial proportion of eligible patients with COPD have not had a coded pulmonary rehabilitation record. Survival was improved in those with PR record but coding for other COPD treatments were also better in this group. GP practices need to improve the coding for PR to highlight any unmet need locally

R2P from Below: Does the British Public View Humanitarian Interventions as Ethical and Effective?

One of the major barriers to the implementation of the Responsibility to Protect principle is the lack of a political will. Public attitudes towards intervention will have a crucial impact on elite willingness to prevent mass atrocities, yet we have little understanding of the factors that influence those attitudes. This article provides the first examination of UK public perceptions about the moral justifiability and effectiveness of humanitarian interventions. The article shows that decisions about justifiability and effectiveness are very different. Attitudes towards justification were more easily explained suggesting that judgements about effectiveness are more contextual and less easily accounted for by individuals’ background characteristics and attitudes. Experiences with both Iraq and Afghanistan have contaminated public perceptions of both the ethics and effectiveness of humanitarian interventions. Although the public is broadly supportive about the justifiability of humanitarian interventions they are extremely sceptical about the likelihood that those interventions will be successful

Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone. In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08). This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.\ud \u

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

Glutamate mediated metabolic neutralization mitigates propionate toxicity in intracellular Mycobacterium tuberculosis

Metabolic networks in biological systems are interconnected, such that malfunctioning parts can be corrected by other parts within the network, a process termed adaptive metabolism. Unlike Bacillus Calmette-Guérin (BCG), Mycobacterium tuberculosis (Mtb) better manages its intracellular lifestyle by executing adaptive metabolism. Here, we used metabolomics and identified glutamate synthase (GltB/D) that converts glutamine to glutamate (Q → E) as a metabolic effort used to neutralize cytoplasmic pH that is acidified while consuming host propionate carbon through the methylcitrate cycle (MCC). Methylisocitrate lyase, the last step of the MCC, is intrinsically downregulated in BCG, leading to obstruction of carbon flux toward central carbon metabolism, accumulation of MCC intermediates, and interference with GltB/D mediated neutralizing activity against propionate toxicity. Indeed, vitamin B12 mediated bypass MCC and additional supplement of glutamate led to selectively correct the phenotypic attenuation in BCG and restore the adaptive capacity of BCG to the similar level of Mtb phenotype. Collectively, a defective crosstalk between MCC and Q → E contributes to attenuation of intracellular BCG. Furthermore, GltB/D inhibition enhances the level of propionate toxicity in Mtb. Thus, these findings revealed a new adaptive metabolism and propose GltB/D as a synergistic target to improve the antimicrobial outcomes of MCC inhibition in Mtb