Frequency dependence of speckle in continuous-wave ultrasound with implications for blood perfusion measurements.

Speckle in continuous wave (CW) Doppler has previously been found to cause large variations in detected Doppler power in blood perfusion measurements, where a large number of blood vessels are present in the sample volume. This artifact can be suppressed by using a number of simultaneously transmitted frequencies and averaging the detected signals. To optimize the strategy, statistical properties of speckle in CW ultrasound need to be known. This paper presents analysis of the frequency separation necessary to obtain independent values of the received power for CW ultrasound using a simplified mathematical model for insonation of a static, lossless, statistically homogeneous, weakly scattering medium. Specifically, the autocovariance function for received power is derived, which functionally is the square of the (deterministic) autocorrelation function of the effective sample volumes produced by the transducer pair for varying frequencies, at least if a delta correlated medium is assumed. A marginal broadening of the modeled autocovariance functions is expected for insonation of blood. The theory is applicable to any transducer aperture, but has been experimentally verified here with 5-MHz, 6.35-mm circular transducers using an agar phantom containing small, randomly dispersed glass particles. A similar experimental verification of a transducer used in multiple-frequency blood perfusion measurements shows that the model proposed in this paper is plausible for explaining the decorrelation between different channels in such a measurement

A new non-invasive ultrasonic method for simultaneous measurements of longitudinal and radial arterial wall movements: first in vivo trial.

During recent years, the radial movement of the arterial wall has been extensively studied, and measurements of the radial movement are now an important tool in cardiovascular research for characterizing the mechanical properties of the arterial wall. In contrast, the longitudinal movement of vessels has gained little or no attention as it has been presumed that this movement is negligible. With modern high-resolution ultrasound, it can, however, be seen that the intima-media complex of the arterial wall moves not only in the radial direction, but also in the longitudinal direction during pulse-wave propagation. This paper describes a new non-invasive ultrasonic method that is able to measure simultaneously two dimensionally arterial vessel wall movements. The method is demonstrated in a limited in vivo trial. Results from the in vivo trial show that, apart from the well-known radial movement, there is a distinct longitudinal movement in the human common carotid artery with, in this case, the intima-media complex moving substantially as compared with the region of the tunica adventitia. Two-dimensional evaluation of the vessel-wall movements, taking not only the radial movement, but also the longitudinal movement into account, may provide novel information of importance in the evaluation of vessel-wall function

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Weather and flying briefing aspects

This course deals with Met Service and aeronautical meteorology aimed at already operational and qualified meteorologists. The objective is not only to give a comprehensive picture of what the pilot or ground service need, but also why. The last part will bring us to the border of and outside of the meteorological field. The compendium contains a base for the above and a starting point for more detailed discussions, adopted to local conditions. Actual and complementary material will be added during the lessons, especially examples where the weather was the major part in accidents/incidents. Thus the main thread through all lessons will be air safety

Weather and flying briefing aspects

This course deals with Met Service and aeronautical meteorology aimed at already operational and qualified meteorologists. The objective is not only to give a comprehensive picture of what the pilot or ground service need, but also why. The last part will bring us to the border of and outside of the meteorological field. The compendium contains a base for the above and a starting point for more detailed discussions, adopted to local conditions. Actual and complementary material will be added during the lessons, especially examples where the weather was the major part in accidents/incidents. Thus the main thread through all lessons will be air safety