Absolute efficiency estimation of photon-number-resolving detectors using twin beams

A nonclassical light source is used to demonstrate experimentally the absolute efficiency calibration of a photon-number-resolving detector. The photon-pair detector calibration method developed by Klyshko for single-photon detectors is generalized to take advantage of the higher dynamic range and additional information provided by photon-number-resolving detectors. This enables the use of brighter twin-beam sources including amplified pulse pumped sources, which increases the relevant signal and provides measurement redundancy, making the calibration more robust

Sex and Ethnic Differences in 47 Candidate Proteomic Markers of Cardiovascular Disease: The Mayo Clinic Proteomic Markers of Arteriosclerosis Study

Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites.Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis.Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment

Single-Nucleotide Polymorphisms in LPA Explain Most of the Ancestry-Specific Variation in Lp(a) Levels in African Americans

Lipoprotein(a) (Lp(a)) is an important causal cardiovascular risk factor, with serum Lp(a) levels predicting atherosclerotic heart disease and genetic determinants of Lp(a) levels showing association with myocardial infarction. Lp(a) levels vary widely between populations, with African-derived populations having nearly 2-fold higher Lp(a) levels than European Americans. We investigated the genetic basis of this difference in 4464 African Americans from the Jackson Heart Study (JHS) using a panel of up to 1447 ancestry informative markers, allowing us to accurately estimate the African ancestry proportion of each individual at each position in the genome. In an unbiased genome-wide admixture scan for frequency-differentiated genetic determinants of Lp(a) level, we found a convincing peak (LOD = 13.6) at 6q25.3, which spans the LPA locus. Dense fine-mapping of the LPA locus identified a number of strongly associated, common biallelic SNPs, a subset of which can account for up to 7% of the variation in Lp(a) level, as well as >70% of the African-European population differences in Lp(a) level. We replicated the association of the most strongly associated SNP, rs9457951 (p = 6×10−22, 27% change in Lp(a) per allele, ∼5% of Lp(a) variance explained in JHS), in 1,726 African Americans from the Dallas Heart Study and found an even stronger association after adjustment for the kringle(IV) repeat copy number. Despite the strong association with Lp(a) levels, we find no association of any LPA SNP with incident coronary heart disease in 3,225 African Americans from the Atherosclerosis Risk in Communities Study

High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing.

BACKGROUND: High sequence identity between segmental duplications (SDs) can facilitate copy number variants (CNVs) via non-allelic homologous recombination (NAHR). These CNVs are one of the fundamental causes of genomic disorders such as the 3q29 deletion syndrome (del3q29S). There are 21 protein-coding genes lost or gained as a result of such recurrent 1.6-Mbp deletions or duplications, respectively, in the 3q29 locus. While NAHR plays a role in CNV occurrence, the factors that increase the risk of NAHR at this particular locus are not well understood. METHODS: We employed an optical genome mapping technique to characterize the 3q29 locus in 161 unaffected individuals, 16 probands with del3q29S and their parents, and 2 probands with the 3q29 duplication syndrome (dup3q29S). Long-read sequencing-based haplotype resolved de novo assemblies from 44 unaffected individuals, and 1 trio was used for orthogonal validation of haplotypes and deletion breakpoints. RESULTS: In total, we discovered 34 haplotypes, of which 19 were novel haplotypes. Among these 19 novel haplotypes, 18 were detected in unaffected individuals, while 1 novel haplotype was detected on the parent-of-origin chromosome of a proband with the del3q29S. Phased assemblies from 44 unaffected individuals enabled the orthogonal validation of 20 haplotypes. In 89% (16/18) of the probands, breakpoints were confined to paralogous copies of a 20-kbp segment within the 3q29 SDs. In one del3q29S proband, the breakpoint was confined to a 374-bp region using long-read sequencing. Furthermore, we categorized del3q29S cases into three classes and dup3q29S cases into two classes based on breakpoints. Finally, we found no evidence of inversions in parent-of-origin chromosomes. CONCLUSIONS: We have generated the most comprehensive haplotype map for the 3q29 locus using unaffected individuals, probands with del3q29S or dup3q29S, and available parents, and also determined the deletion breakpoint to be within a 374-bp region in one proband with del3q29S. These results should provide a better understanding of the underlying genetic architecture that contributes to the etiology of del3q29S and dup3q29S

Quantum states made to measure

Recent progress in manipulating quantum states of light and matter brings quantum-enhanced measurements closer to prospective applications. The current challenge is to make quantum metrologic strategies robust against imperfections.Comment: 4 pages, 3 figures, Commentary for Nature Photonic

Unified View of Scaling Laws for River Networks

Scaling laws that describe the structure of river networks are shown to follow from three simple assumptions. These assumptions are: (1) river networks are structurally self-similar, (2) single channels are self-affine, and (3) overland flow into channels occurs over a characteristic distance (drainage density is uniform). We obtain a complete set of scaling relations connecting the exponents of these scaling laws and find that only two of these exponents are independent. We further demonstrate that the two predominant descriptions of network structure (Tokunaga's law and Horton's laws) are equivalent in the case of landscapes with uniform drainage density. The results are tested with data from both real landscapes and a special class of random networks.Comment: 14 pages, 9 figures, 4 tables (converted to Revtex4, PRE ref added

Hypertension in Pregnancy Is a Risk Factor for Microalbuminuria Later in Life

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99687/1/jch12116.pd

Covert Neurological Symptoms Associated With Silent Infarcts From Midlife to Older Age: The Atherosclerosis Risk in Communities Study

Unrecognized or unreported stroke-like symptoms, called covert symptoms, occur in persons free of clinical stroke. Whether covert symptoms are associated with subclinical brain infarcts (SBI) is unknown. This study examined the association between covert stroke-like symptoms and SBI/stroke in persons with no history of stroke or TIA

Metabolomics and Incident Hypertension Among Blacks: The Atherosclerosis Risk in Communities Study

Development of hypertension is influenced by genes, environmental effects and their interactions, and the human metabolome is a measurable manifestation of gene-environment interaction. We explored the metabolomic antecedents of developing incident hypertension in a sample of African Americans, a population with a high prevalence of hypertension and its comorbidities. We examined 896 (565 females, aged 45–64 years) African American normotensives from the Atherosclerosis Risk in Communities (ARIC) Study, whose metabolome was measured in serum collected at the baseline examination and analyzed by high throughput methods. The analyses presented here focus on 204 stably measured metabolites over a period of 4–6 weeks. Weibull parametric models considering interval censored data were used to assess the hazard ratio for incident hypertension. We used a modified Bonferroni correction accounting for the correlations among metabolites to define a threshold for statistical significance (p<3.9×10−4). During 10-years of follow-up, 38% of baseline normotensives developed hypertension (N=344). With adjustment for traditional risk factors and estimated glomerular filtration rate, each +1-standard deviation difference in baseline 4-hydroxyhippurate, a product of gut microbial fermentation, was associated with 17% higher risk of hypertension (p=2.5×10−4), which remained significant after adjusting for both baseline systolic and diastolic blood pressure (p=3.8×10−4). After principal component analyses, a sex steroids pattern was significantly associated with risk of incident hypertension (highest versus lowest quintile hazard ratio, 1.72; 95% CI, 1.05 to 2.82; p for trend=0.03), and stratified analyses suggested that this association was consistent in both genders. Metabolomic analyses identify novel pathways in the etiology of hypertension