Generation of Entangled N-Photon States in a Two-Mode Jaynes-Cummings Model

We describe a mathematical solution for the generation of entangled N-photon states in two field modes. A simple and compact solution is presented for a two-mode Jaynes-Cummings model by combining the two field modes in a way that only one of the two resulting quasi-modes enters in the interaction term. The formalism developed is then applied to calculate various generation probabilities analytically. We show that entanglement, starting from an initial field and an atom in one defined state may be obtained in a single step. We also show that entanglement may be built up in the case of an empty cavity and excited atoms whose final states are detected, as well as in the case when the final states of the initially excited atoms are not detected.Comment: v2: 5 pages, RevTeX4, minor text changes + 1 figure added, revised version to be published in PRA, May 200

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

Development and external validation of a deep learning algorithm for prognostication of cardiovascular outcomes

Background and Objectives: We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression. Methods: Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): A Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included. Results: Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886-0.907) in men and 0.921 (0.908-0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860-0.876) in men and 0.889 (0.876-0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824-0.897) in men and 0.867 (0.830-0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women). Conclusions: A DL algorithm exhibited greater discriminative accuracy than Cox model approaches

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries:23 million person-years of observation

Background:The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods:For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes.</p

Social health and change in cognitive capability among older adults:findings from four European longitudinal studies

Introduction: In this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. Methods: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. Results: Pooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (≥6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous. Conclusion: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any intervention

Quantum entanglement and disentanglement of multi-atom systems

We present a review of recent research on quantum entanglement, with special emphasis on entanglement between single atoms, processing of an encoded entanglement and its temporary evolution. Analysis based on the density matrix formalism are described. We give a simple description of the entangling procedure and explore the role of the environment in creation of entanglement and in disentanglement of atomic systems. A particular process we will focus on is spontaneous emission, usually recognized as an irreversible loss of information and entanglement encoded in the internal states of the system. We illustrate some certain circumstances where this irreversible process can in fact induce entanglement between separated systems. We also show how spontaneous emission reveals a competition between the Bell states of a two qubit system that leads to the recently discovered "sudden" features in the temporal evolution of entanglement. An another problem illustrated in details is a deterministic preparation of atoms and atomic ensembles in long-lived stationary squeezed states and entangled cluster states. We then determine how to trigger the evolution of the stable entanglement and also address the issue of a steered evolution of entanglement between desired pairs of qubits that can be achieved simply by varying the parameters of a given system.Comment: Review articl

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP-001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 7 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions

Admixture Mapping Scans Identify a Locus Affecting Retinal Vascular Caliber in Hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) Study

Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (ρ = 0.071, P = 0.003), but not CRAE (ρ = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = −0.73) or CRVE (genome-wide score = −0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 µm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension