The smoothing and forecasting of discrete time series that occur at random review intervals of time

Implicit in the classical techniques of smoothing and forecasting of discrete time series is the restriction that the data spans equal intervals of time. There exists a need to make forecasts at unequal time intervals for the transactio or even oriented business activity

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Data from: Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Objective: We explored genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely small sub-cortical BI (SSBI), in eighteen population-based cohorts (N=20,949) from five ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in seven population-based cohorts (N=6,862, 1,483 with BI, 630 with SBBI), and tested associations with related phenotypes including ischemic stroke and pathologically-defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, P=1.77×10-8 and LINC00539/ZDHHC20, P=5.82×10-9. Both have been associated with blood pressure (BP) related phenotypes, but did not replicate in the smaller follow-up sample nor show associations with related phenotypes. Age and sex-adjusted associations with BI and SSBI were observed for BP traits (P-value for BI, P[BI]=9.38×10-25; P[SSBI]=5.23×10-14 for hypertension), smoking (P[BI]=4.4×10-10; P[SSBI]=1.2×10-4), diabetes (P[BI]=1.7×10-8; P[SSBI]=2.8×10-3), previous cardiovascular disease (P[BI]=1.0×10-18; P[SSBI]=2.3×10-7), stroke (P[BI]=3.9×10-69; P[SSBI]=3.2×10-24), and MRI-defined white matter hyperintensity burden (P[BI]=1.43×10-157; P[SSBI]=3.16×10-106), but not with body-mass-index or cholesterol. GRS of BP traits were associated with BI and SSBI (P≤0.0022), without indication of directional pleiotropy. Conclusions: In this multi-ethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based study - Supplemental data

This file contains the supplemental data to the article entitled "Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based study". It contains additional methods paragraphs 1 to 4, supplemental tables 1 to 17, supplemental figures 1 to 7, and additional reference

SEIS: Insight’s Seismic Experiment for Internal Structure of Mars

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars’ surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking’s Mars seismic monitoring by a factor of ∼2500 at 1 Hz and ∼200000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars’ surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of ∼3 at 40∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points