217 research outputs found

    The particle number in Galilean holography

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    Recently, gravity duals for certain Galilean-invariant conformal field theories have been constructed. In this paper, we point out that the spectrum of the particle number operator in the examples found so far is not a necessary consequence of the existence of a gravity dual. We record some progress towards more realistic spectra. In particular, we construct bulk systems with asymptotic Schrodinger symmetry and only one extra dimension. In examples, we find solutions which describe these Schrodinger-symmetric systems at finite density. A lift to M-theory is used to resolve a curvature singularity. As a happy byproduct of this analysis, we realize a state which could be called a holographic Mott insulator.Comment: 29 pages, 1 rudimentary figure; v2: typo in eqn (3.4), added comments and ref

    Adaptive Evolution of Escherichia coli to an α-Peptide/β-Peptoid Peptidomimetic Induces Stable Resistance.

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    Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved structures of bacterial cell envelopes and hence, development of resistance has been considered an unlikely event. However, recently bacterial resistance to AMPs has been observed, and the aim of the present study was to determine whether bacterial resistance may also evolve against synthetic AMP analogues, e.g. α-peptide/β-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10 lineages), or MilliQ water (4 lineages) in a re-inoculation culturing setup covering approx. 500 generations. All 10 lineages exposed to the peptidomimetic adapted to 32 × MIC while this occurred for 8 out of 10 of the polymyxin B-exposed lineages. All lineages exposed to 32 × MIC of either the peptidomimetic or polymyxin B had a significantly increased MIC (16-32 ×) to the selection agent. Five transfers (≈ 35 generations) in unsupplemented media did not abolish resistance indicating that resistance was heritable. Single isolates from peptidomimetic-exposed lineage populations displayed MICs against the peptidomimetic from wild-type MIC to 32 × MIC revealing heterogeneous populations. Resistant isolates showed no cross-resistance against a panel of membrane-active AMPs. These isolates were highly susceptible to blood plasma antibacterial activity and were killed when plasma concentrations exceeded ≈ 30%. Notably, MIC of the peptidomimetic against resistant isolates returned to wild-type level upon addition of 25% plasma. Whole-genome sequencing of twenty isolates from four resistant lineages revealed mutations, in murein transglycosylase D (mltD) and outer-membrane proteins, which were conserved within and between lineages. However, no common resistance-conferring mutation was identified. We hypothesise that alterations in cell envelope structure result in peptidomimetic resistance, and that this may occur via several distinct mechanisms. Interestingly, this type of resistance result in a concomitant high susceptibility towards plasma, and therefore the present study does not infer additional concern for peptidomimetics as future therapeutics

    Genome of the facultative scuticociliatosis pathogen Pseudocohnilembus persalinus provides insight into its virulence through horizontal gene transfer

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The attached file is the published version of the article

    Utilization and responsiveness of the asthma control test (ACT) at the initiation of therapy for patients with asthma: a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the responsiveness of the asthma control test (ACT) to detect changes at the initiation of therapy and its utilization in the initiation of asthma treatment.</p> <p>Methods</p> <p>This study was designed as a randomized clinical trial conducted in a primary care setting. The subjects were asthma patients who had not received controller therapy for at least two months. The patients were randomized into two groups: The Saudi Initiative for Asthma (SINA) group and the Global Initiative for Asthma (GINA) group. Treatment in the SINA group was initiated at step1 when the ACT scores ≥ 20, step 2 when the score between16-19, and step 3 when the score < 16 began at step 3. The GINA group patients were started on step 2 when they had persistent asthma symptoms or step 3 when they had severely uncontrolled disease.</p> <p>Results</p> <p>Forty-five patients were analyzed in each group. The improvement in ACT score after treatment initiation was significantly higher when the SINA approach was used (2.9 in the SINA group compared to 1.7 in the GINA group (<it>p </it>= 0.04)). The improvement in FEV<sub>1 </sub>was 5.8% in the SINA group compared to 3.4% in the GINA group (<it>p </it>= 0.46). The number of patients who achieved asthma control at the follow-up visit and required no treatment adjustment was 33 (73.3%) in the SINA group and 27 (60%) in the GINA group (<it>p </it>= 0.0125).</p> <p>Conclusion</p> <p>The ACT was responsive to change at the initiation of asthma treatment and was useful for the initiation of asthma treatment.</p> <p>Trial Registration number</p> <p><a href="http://www.controlled-trials.com/ISRCTN31998214">ISRCTN31998214</a></p

    Hospital admissions and deaths relating to deliberate self-harm and accidents within 5 years of a cancer diagnosis: a national study in Scotland, UK

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    The risk of suicide in cancer patients has been reported as elevated in several countries. These patients are exposed to many medicines that may confuse or provide a means for harm, potentially also increasing their risk from accidents. Ratios of observed/expected numbers of hospital admission and death events relating to deliberate self-harm (DSH) and accidents were calculated in the 5 years from a cancer diagnosis in Scotland 1981–1995, compared to the matched general population. The relative risk (RR) of suicide was 1.51 (95% confidence interval (CI): 1.29–1.76). The RR of hospital admissions for DSH was not significantly increased, suggesting a strong suicidal intent in DSH acts in cancer patients. Accidental poisonings and all other accidents were both increased (RR death=3.69, 95% CI: 2.10–6.00; and 1.58, 95% CI: 1.48–1.69, respectively) (RR hospital admissions=1.32, 95% CI: 1.19–1.47; and 1.55, 95% CI: 1.53–1.57, respectively). The association of only certain tumour types (e.g. respiratory) with suicide and accidental poisoning, and a broad range of tumour types with an elevated risk of all other accidents, suggests accidental poisoning categories may be a common destination for code shifting of some DSH events. A previous history of DSH or accidents, significantly increased the RR of suicide or fatal accidents, respectively (RR suicide=14.86 (95% CI: 4.69–34.97) vs 1.16 (95% CI: 0.84–1.55)) (RR accidental death=3.37 (95% CI: 2.53–4.41) vs 1.29 (95% CI: 1.12–1.49)). Within 5 years of a cancer diagnosis, Scottish patients are at increased RR of suicide and fatal accidents, and increased RR of hospital admissions for accidents. Some of these accidents, particularly accidental poisonings, may contain hidden deliberate acts. Previous DSH or accidents are potential markers for those most at risk, in whom to target interventional techniques

    Increased production of IL-4 and IL-12p40 from bronchoalveolar lavage cells are biomarkers of Mycobacterium tuberculosis in the sputum

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    BACKGROUND: Tuberculosis (TB) causes 1.45 million deaths annually world wide, the majority of which occur in the developing world. Active TB disease represents immune failure to control latent infection from airborne spread. Acid-fast bacillus (AFB) seen on sputum smear is a biomarker for contagiousness. METHODS: We enrolled 73 tuberculosis patients with extensive infiltrates into a research study using bronchoalveolar lavage (BAL) to sample lung immune cells and assay BAL cell cytokine production. All patients had sputum culture demonstrating Mycobacterium tuberculosis and 59/73 (81%) had AFB identified by microscopy of the sputum. Compared with smear negative patients, smear positive patients at presentation had a higher proportion with smoking history, a higher proportion with temperature >38.5 0 C, higher BAL cells/ml, lower percent lymphocytes in BAL, higher IL-4 and IL-12p40 in BAL cell supernatants. There was no correlation between AFB smear and other BAL or serum cytokines. Increasing IL-4 was associated with BAL PMN and negatively associated with BAL lymphocytes. Each 10-fold increase in BAL IL-4 and IL-12p40 increased the odds of AFB smear positivity by 7.4 and 2.2-fold, respectively, in a multi-variable logistic model. CONCLUSION: Increasing IL-4 and IL-12p40 production by BAL cells are biomarkers for AFB in sputum of patients who present with radiographically advanced TB. They likely reflect less effective immune control of pathways for controlling TB, leading to patients with increased infectiousness
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