Narrowband frequency tunable light source of continuous quadrature entanglement

We report the observation of non-classical quantum correlations of continuous light variables from a novel type of source. It is a frequency non-degenerate optical parametric oscillator below threshold, where signal and idler fields are separated by 740MHz corresponding to two free spectrum ranges of the parametric oscillator cavity. The degree of entanglement observed, - 3.8 dB, is the highest to-date for a narrowband tunable source suitable for atomic quantum memory and other applications in atomic physics. Finally we use the latter to visualize the Einstein-Podolsky-Rosen paradox.Comment: 11 pages, 9 figures, LaTe

Heart failure associated with imported malaria:a nationwide Danish cohort study

Abstract Aims Despite adequate treatment, recent studies have hypothesized that malaria may affect long‐term cardiovascular function. We aimed to investigate the long‐term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark. Methods Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all‐cause death (1 January 1994 to 1 January 2017). The population was age‐ and sex‐matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion. Results We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow‐up was 9.8 years (interquartile range 3.9–16.4 years). Event rates per 1000 person‐years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all‐cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21–2.09], P = 0.001), but not MI (HR: 1.00 [0.72–1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74–1.35], P = 0.98) or all‐cause death (HR 1.11 [0.94–1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14–2.36], P = 0.008). Conclusion Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF

Mannose-binding lectin deficiency with eosinophilic meningoencephalitis due to Angiostrongylus cantonensis in children: a case series

<p>Abstract</p> <p>Introduction</p> <p>Eosinophilic meningitis, a potentially fatal disease caused by <it>Angiostrongylus cantonensis</it>, is considered an emerging infectious disease.</p> <p>Case presentation</p> <p>Three Caucasian boys (aged five-years-old, 10-years-old and six-years-old) with a diagnosis of eosinophilic meningoencephalitis caused by <it>Angiostrongylus cantonensis </it>were studied. Serum immunoglobulin A (IgA), IgM, IgG, and complements C3c and C4 levels were quantified by using an immunodiffusion technique. Immunoglobulin E in serum was quantified by nephelometry and mannose-binding lectin by time-resolved fluorometry. Mannose-binding lectin deficiency was observed in the three patients. The first patient showed a reduction in the levels of IgA and IgM and an increase in the values of IgE and C4. The second patient showed a reduction in mannose-binding lectin level with increased IgG, C4 and IgE levels, and the third patient showed a decrease in mannose-binding lectin level and increased levels of IgM and complement C3c as well as a low level of C4.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of mannose-binding lectin deficiency associated with <it>Angiostrongylus cantonensis </it>meningoencephalitis in children, and it may contribute to the understanding of the participation of this component of the lectin pathway in the development of the disease.</p

Integrated care for older multimorbid heart failure patients:protocol for the ESCAPE randomized trial and cohort study

ESCAPE Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multimorbid elderly patients. Therapeutic Area Healthcare interventions for the management of older patients with multiple morbidities. Aims Multi-morbidity treatment is an increasing challenge for healthcare systems in ageing societies. This comprehensive cohort study with embedded randomized controlled trial tests an integrated biopsychosocial care model for multimorbid elderly patients. Hypothesis A holistic, patient-centred pro-active 9-month intervention based on the blended collaborative care (BCC) approach and enhanced by information and communication technologies can improve health-related quality of life (HRQoL) and disease outcomes as compared with usual care at 9 months. Methods Across six European countries, ESCAPE is recruiting patients with heart failure, mental distress/disorder plus ≥2 medical co-morbidities into an observational cohort study. Within the cohort study, 300 patients will be included in a randomized controlled assessor-blinded two-arm parallel group interventional clinical trial (RCT). In the intervention, trained care managers (CMs) regularly support patients and informal carers in managing their multiple health problems. Supervised by a clinical specialist team, CMs remotely support patients in implementing the treatment plan—customized to the patients' individual needs and preferences—into their daily lives and liaise with patients' healthcare providers. An eHealth platform with an integrated patient registry guides the intervention and helps to empower patients and informal carers. HRQoL measured with the EQ-5D-5L as primary endpoint, and secondary outcomes, that is, medical and patient-reported outcomes, healthcare costs, cost-effectiveness, and informal carer burden, will be assessed at 9 and ≥18 months. Conclusions If proven effective, the ESCAPE BCC intervention can be implemented in routine care for older patients with multiple morbidities across the participating countries and beyond

Hippocampal pyramidal cells: the reemergence of cortical lamination

The increasing resolution of tract-tracing studies has led to the definition of segments along the transverse axis of the hippocampal pyramidal cell layer, which may represent functionally defined elements. This review will summarize evidence for a morphological and functional differentiation of pyramidal cells along the radial (deep to superficial) axis of the cell layer. In many species, deep and superficial sublayers can be identified histologically throughout large parts of the septotemporal extent of the hippocampus. Neurons in these sublayers are generated during different periods of development. During development, deep and superficial cells express genes (Sox5, SatB2) that also specify the phenotypes of superficial and deep cells in the neocortex. Deep and superficial cells differ neurochemically (e.g. calbindin and zinc) and in their adult gene expression patterns. These markers also distinguish sublayers in the septal hippocampus, where they are not readily apparent histologically in rat or mouse. Deep and superficial pyramidal cells differ in septal, striatal, and neocortical efferent connections. Distributions of deep and superficial pyramidal cell dendrites and studies in reeler or sparsely GFP-expressing mice indicate that this also applies to afferent pathways. Histological, neurochemical, and connective differences between deep and superficial neurons may correlate with (patho-) physiological phenomena specific to pyramidal cells at different radial locations. We feel that an appreciation of radial subdivisions in the pyramidal cell layer reminiscent of lamination in other cortical areas may be critical in the interpretation of studies of hippocampal anatomy and function

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.Peer reviewe

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg-0.22, P =5.5x10-13), T2D (rg-0.27, P =1.1x10-6) and coronary artery disease (rg-0.30, P =6.5x10-9) and, in large cohort data sets, demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated