Ultra-broadband photon pair preparation by spontaneous four wave mixing in dispersion-engineered optical fiber

We present a study of the spectral properties of photon pairs generated through the process of spontaneous four wave mixing (SFWM) in single mode fiber. Our analysis assumes narrowband pumps, which are allowed to be frequency-degenerate or non-degenerate. Based on this analysis, we derive conditions on the pump frequencies and on the fiber dispersion parameters which guarantee the generation of ultra-broadband photon pairs. Such photon pairs are characterized by: i) a very large degree of entanglement, and ii) a very high degree of temporal synchronization between the signal and idler photons. Through a numerical exercise, we find that the use of photonic crystal fiber (PCF) facilitates the fulfilment of the conditions for ultra-broadband photon pair generation; in particular, the spectral region in which emission occurs can be adjusted to particular needs through an appropriate choice of the PCF parameters. In addition, we present a novel quantum interference effect, resulting from indistinguishable pathways to the same outcome, which can occur when pumping a SFWM source with multiple spectral lines.Comment: 15 pages, 10 figures. To be published in Phys. Rev.

Epidermal Loss of Gag Confers a Migratory and Differentiation Defect in Keratinocytes

G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gaq and Ga-11, activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Ga-11 and Gaq from endothelial cells impairs the Rho -mediated formation of focal adherens junctions, suggesting that Gai vg signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells. Indeed, combined deletion of Ga-11 and Gaq confers a significant migratory defect in keratinocytes that delays cutaneous wound healing in an in vivo setting. This delay can be attributed to a defect during the reepithelialization phase due to significantly attenuated migratory capacity of Gaq-null keratinocytes under combined Ga-11 deficiency. In fact, cells lacking Gaivg demonstrate a severely reduced ability to respond to mitogenic and migratory signals in the microenvironment, leading to inappropriate and premature terminal differentiation. These results suggest that Gaivg signaling pathways may be critical for integrating mitogenic signals and cytoskeletal function to achieve normal physiological responses. Emergence of a malignant phenotype may therefore arise from both under- and overexpression of Gai vg signaling, implicating its upstream regulation as a potential therapeutic target in a host of pathologic conditions

Urinary incontinence related to perineal muscle strength in the first trimester of pregnancy: cross-sectional study

Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.
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Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism Pooled Analysis of Five Prospective General Population Cohorts

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from five community-based cohorts from Europe (HUNT2, PREVEND and Tromsø study) and United States (ARIC and CHS study) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria and CKD with objectively verified VTE. To estimate adjusted hazard ratios (HRs) for VTE, categorical and continuous spline models were fit using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1,178 VTE events occurred over 599,453 person-years follow-up. Relative to eGFR 100 mL/min/1.73m(2), HRs for VTE were 1.29 (95%CI, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for 60, 1.82 (1.27-2.60) for 45 and 1.95 (1.26-3.01) for 30 mL/min/1.73m(2). Compared with albumin-creatinine ratio (ACR) of 5.0 mg/g, the HRs for VTE were 1.34 (1.04-1.72) for 30 mg/g, 1.60 (1.08-2.36) for 300 mg/g and 1.92 (1.19-3.09) for 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted HR for CKD defined as eGFR <60 mL/min/1.73m(2) or albuminuria ≥30 mg/g (vs. no CKD) was 1.54 (95%CI, 1.15-2.06). Associations were consistent in subgroups according to age, gender, and comorbidities as well as for unprovoked versus provoked VTE. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges

The Sertindole Safety Survey: A retrospective analysis under a named patient use programme in Europe

<p>Abstract</p> <p>Background</p> <p>After sertindole's suspension, health authorities established a specific named-patient use (NPU) programme in order to supply sertindole to patients who did not respond to or did not tolerate alternative treatments. This programme provided the possibility of prospectively following an exhaustive cohort of patients treated with sertindole after its suspension. A survey was performed to assess sertindole's modalities of prescription, assess and document any serious adverse events (SAEs), and assess the mortality rate within the NPU cohort.</p> <p>Methods</p> <p>The study comprised a survey of sertindole-treated patients in eleven European countries. All patients treated with sertindole within the NPU programme were eligible for the study.</p> <p>Results</p> <p>1,432 patients were included in the study. The reason for sertindole prescription was lack of efficacy (approximately 50%) or adverse events (approximately 20%) of other antipsychotic treatments. The mean sertindole dose was 13.4 mg daily. Lack of efficacy and adverse events were reported as reasons for sertindole discontinuation.</p> <p>A total of 97 SAEs were recorded, including ten fatal outcomes, which occurred during the study period or within thirty days after sertindole discontinuation. The all-cause mortality rate was 0.51 per 100 Person-Years of Exposure (95% Poisson confidence interval: 0.23–0.97). QTc prolongation was reported in 15 patients (1.05% of total patients), being a rate of 0.85 per 100 Person-Years of Exposure [95% CI: 0.48–1.41].</p> <p>Conclusion</p> <p>Although prescribing and supplying sertindole were subject to administrative constraints, a significant number of patients were treated with sertindole, thus supporting the need for sertindole in specific cases.</p> <p>Trial registration number</p> <p>Not applicable.</p

IGHV-associated methylation signatures more accurately predict clinical outcomes of chronic lymphocytic leukemia patients than IGHV mutation load

Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P &lt; 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition