Intestinal colonization due to Escherichia coli ST131: Risk factors and prevalence

Background Escherichia coli sequence type 131 (ST131) is a successful clonal group that has dramatically spread during the last decades and is considered an important driver for the rapid increase of quinolone resistance in E. coli. Methods Risk factors for rectal colonization by ST131 Escherichia coli (irrespective of ESBL production) were investigated in 64 household members (18 were colonized) and 54 hospital contacts (HC; 10 colonized) of 34 and 30 index patients with community and nosocomial infection due to these organisms, respectively, using multilevel analysis with a p limit of < 0.1. Result Colonization among household members was associated with the use of proton-pump inhibitors (PPI) by the household member (OR = 3.08; 95% CI: 0.88–10.8) and higher age of index patients (OR = 1.05; 95% CI; 1.01–1.10), and among HC, with being bed-ridden (OR = 21.1; 95% CI: 3.61–160.0) and having a urinary catheter (OR = 8.4; 95% CI: 0.87–76.9). Conclusion Use of PPI and variables associated with higher need of person-to-person contact are associated with increased risk of rectal colonization by ST131. These results should be considered for infection control purposes.Plan Nacional de I + D + i 2013-2016Ministerio de Economía y Competitividad (España)European Development Regional Fund REIPI RD12/0015/0010 REIPI RD16/0016/0001Instituto de Salud Carlos III 070190 AC16/000076-MODERN AC16/AC16/00072-ST131TSJunta de Andalucía CTS5259 CTS21

Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

<p>Abstract</p> <p>Background</p> <p>Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.</p> <p>Methods</p> <p>Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed.</p> <p>Results</p> <p>The mean loss of FEV₁was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV₁of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV₁and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV₁and FVC was demonstrated (3 months ΔFEV₁: 220 ± 82 ml, p = 0.024; 6 months ΔFEV₁: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy.</p> <p>Conclusions</p> <p>Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.</p

Quantum resource estimates for computing elliptic curve discrete logarithms

We give precise quantum resource estimates for Shor's algorithm to compute discrete logarithms on elliptic curves over prime fields. The estimates are derived from a simulation of a Toffoli gate network for controlled elliptic curve point addition, implemented within the framework of the quantum computing software tool suite LIQ$Ui|\rangle$. We determine circuit implementations for reversible modular arithmetic, including modular addition, multiplication and inversion, as well as reversible elliptic curve point addition. We conclude that elliptic curve discrete logarithms on an elliptic curve defined over an $n$-bit prime field can be computed on a quantum computer with at most $9n + 2\lceil\log_2(n)\rceil+10$ qubits using a quantum circuit of at most $448 n^3 \log_2(n) + 4090 n^3$ Toffoli gates. We are able to classically simulate the Toffoli networks corresponding to the controlled elliptic curve point addition as the core piece of Shor's algorithm for the NIST standard curves P-192, P-224, P-256, P-384 and P-521. Our approach allows gate-level comparisons to recent resource estimates for Shor's factoring algorithm. The results also support estimates given earlier by Proos and Zalka and indicate that, for current parameters at comparable classical security levels, the number of qubits required to tackle elliptic curves is less than for attacking RSA, suggesting that indeed ECC is an easier target than RSA.Comment: 24 pages, 2 tables, 11 figures. v2: typos fixed and reference added. ASIACRYPT 201

Effects of Thyroxine Exposure on Osteogenesis in Mouse Calvarial Pre-Osteoblasts

The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis. © 2013 Cray et al

Triplet-Singlet Spin Relaxation via Nuclei in a Double Quantum Dot

The spin of a confined electron, when oriented originally in some direction, will lose memory of that orientation after some time. Physical mechanisms leading to this relaxation of spin memory typically involve either coupling of the electron spin to its orbital motion or to nuclear spins. Relaxation of confined electron spin has been previously measured only for Zeeman or exchange split spin states, where spin-orbit effects dominate relaxation, while spin flips due to nuclei have been observed in optical spectroscopy studies. Using an isolated GaAs double quantum dot defined by electrostatic gates and direct time domain measurements, we investigate in detail spin relaxation for arbitrary splitting of spin states. Results demonstrate that electron spin flips are dominated by nuclear interactions and are slowed by several orders of magnitude when a magnetic field of a few millitesla is applied. These results have significant implications for spin-based information processing

An analysis of temporal and generational trends in the incidence of anal and other HPV-related cancers in Southeast England

Patients diagnosed in 1960–2004 with cancer of the cervix, anus, vulva, vagina or penis were identified from the Thames Cancer Registry database, and age-standardised period (temporal) incidence rates calculated by direct standardisation. Age-cohort modelling techniques were used to estimate age-specific incidence rates in the earlier and later cohorts, enabling the calculation of age-standardised cohort (generational) rates. Incidence of anal cancer increased for both men and women over the period studied, mainly in those born from 1940 onwards. Similar generational patterns were seen for cancers of the vulva and vagina, but those for penile cancer were different. For cervix cancer, the steep downward trend in cohort rates due to screening levelled off in women born from 1940 onwards. Our findings are compatible with the hypothesis that changes in sexual practices were a major contributor to the increases of these cancers. Programmes of vaccination against HPV, aimed at reducing the burden of cervical cancer, may also help to reduce the incidence of cancer at other anogenital sites

Sparse, continuous policy representations for uniform online bin packing via regression of interpolants

Online bin packing is a classic optimisation problem, widely tackled by heuristic methods. In addition to human-designed heuristic packing policies (e.g. first- or best- fit), there has been interest over the last decade in the automatic generation of policies. One of the main limitations of some previously-used policy representations is the trade-off between locality and granularity in the associated search space. In this article, we adopt an interpolation-based representation which has the jointly-desirable properties of being sparse and continuous (i.e. exhibits good genotype-to-phenotype locality). In contrast to previous approaches, the policy space is searchable via real-valued optimization methods. Packing policies using five different interpolation methods are comprehensively compared against a range of existing methods from the literature, and it is determined that the proposed method scales to larger instances than those in the literature

Copy-number variation in BMPR2 is not associated with the pathogenesis of pulmonary arterial hypertension

<p>Abstract</p> <p>Background</p> <p>Copy-number variations (CNVs) are structural variations in the genome involving 1 kb to 3 mb of DNA. CNV has been reported within intron 1 of the <it>BMPR2 </it>gene. We propose that CNV could affect phenotype in familial and/or sporadic pulmonary arterial hypertension (PAH) by altering gene expression.</p> <p>Methods</p> <p>97 human DNA samples were obtained which included 24 patients with familial PAH, 18 obligate carriers (<it>BMPR2 </it>mutation positive), 20 sporadic PAH patients, and 35 controls. Two sets of primers were designed within the CNV, and two sets of control primers were designed outside the CNV. Quantitative PCR was performed to quantify genomic copies of CNV and control sequences.</p> <p>Results</p> <p>A CNV in <it>BMPR2 </it>was present in one African American negative control subject.</p> <p>Conclusion</p> <p>We conclude that the CNV in intron 1 in <it>BMPR2 </it>is unlikely to play a role in the pathogenesis of either familial or sporadic PAH.</p> <p>Trial Registration</p> <p>NIH NCT00091546.</p

Older employees' declining attitudes over 20 years and across classes

British employers, under increasing competitive pressures, and applying new technology and work organization, have sought to reduce labour costs, resulting in work intensification and precarity. Older employees as a result are exposed to work demands that conflict with expectations of favourable treatment in late career. National survey data for Britain in the years 1992, 2001, 2006 and 2012 demonstrate a decline in overall job attitude among older employees following the changed conditions of the 1990s and across the major recession that began in 2008. To assess whether this decline is unequally distributed, decomposition by socio-economic class is carried out. This shows that older employees in the ‘service class’ of managerial and professional employees are affected at least as much as older employees in intermediate and less-skilled classes, thus underlining the age effect and showing that ‘service-class’ employees are not invulnerable to a changing economic environment