An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention

The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant’s impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18–1.92], p = 0.00096), peripheral artery disease (1.69 [1.01–2.82], p = 0.046), and coronary operations (1.78 [1.21–2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations

Loss of sucrase-isomaltase function increases acetate levels and improves metabolic health in Greenlandic cohorts

Background & Aims The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. Methods The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. Results Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β [standard error], –2.0 [0.5] kg/m2; P = 3.1 × 10–5), body weight (–4.8 [1.4] kg; P = 5.1 × 10–4), fat percentage (–3.3% [1.0%]; P = 3.7 × 10–4), fasting triglyceride (–0.27 [0.07] mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 [0.03] mmol/L; P = 4.2 × 10–5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (β [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. Conclusions These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate

NA61/SHINE facility at the CERN SPS: beams and detector system

NA61/SHINE (SPS Heavy Ion and Neutrino Experiment) is a multi-purpose experimental facility to study hadron production in hadron-proton, hadron-nucleus and nucleus-nucleus collisions at the CERN Super Proton Synchrotron. It recorded the first physics data with hadron beams in 2009 and with ion beams (secondary 7Be beams) in 2011. NA61/SHINE has greatly profited from the long development of the CERN proton and ion sources and the accelerator chain as well as the H2 beamline of the CERN North Area. The latter has recently been modified to also serve as a fragment separator as needed to produce the Be beams for NA61/SHINE. Numerous components of the NA61/SHINE set-up were inherited from its predecessors, in particular, the last one, the NA49 experiment. Important new detectors and upgrades of the legacy equipment were introduced by the NA61/SHINE Collaboration. This paper describes the state of the NA61/SHINE facility - the beams and the detector system - before the CERN Long Shutdown I, which started in March 2013

String Theory on AdS Orbifolds

We consider worldsheet string theory on $Z_N$ orbifolds of $AdS_3$ associated with conical singularities. If the orbifold action includes a similar twist of $S^3$, supersymmetry is preserved, and there is a moduli space of vacua arising from blowup modes of the orbifold singularity. We exhibit the spectrum, including the properties of twisted sectors and states obtained by fractional spectral flow. A subalgebra of the spacetime superconformal symmetry remains intact after the $Z_N$ quotient, and serves as the spacetime symmetry algebra of the orbifold.Comment: 37 pages, 3 eps figures. v2: Substantial revision to section 7, on spacetime CFT interpretatio

Power spectrum analysis of ionospheric fluctuations with the Murchison Widefield Array

Low-frequency, wide field-of-view (FOV) radio telescopes such as the Murchison Widefield Array (MWA) enable the ionosphere to be sampled at high spatial completeness. We present the results of the first power spectrum analysis of ionospheric fluctuations in MWA data, where we examined the position offsets of radio sources appearing in two data sets. The refractive shifts in the positions of celestial sources are proportional to spatial gradients in the electron column density transverse to the line of sight. These can be used to probe plasma structures and waves in the ionosphere. The regional (10–100 km) scales probed by the MWA, determined by the size of its FOV and the spatial density of radio sources (typically thousands in a single FOV), complement the global (100–1000 km) scales of GPS studies and local (0.01–1 km) scales of radar scattering measurements. Our data exhibit a range of complex structures and waves. Some fluctuations have the characteristics of traveling ionospheric disturbances, while others take the form of narrow, slowly drifting bands aligned along the Earth's magnetic field

Hidden strangeness shines in NA61/SHINE

Preliminary results on the ϕ (1020) meson production in inelastic proton-proton collisions measured by the NA61/SHINE experiment at the CERN SPS are presented in these proceedings. The results include the first ever differential pT and y measurements at beam momenta of 40 and 80 GeV and the most ever detailed experimental data at 158GeV. The comparison of p + p to Pb + Pb results shows a non-trivial system size dependence of the widths of the rapidity distributions for ϕ mesons, contrasting with that of other hadrons. The results are furthermore compared to the world data on ϕ meson production, demonstrating the better accuracy achieved by the NA61/SHINE experiment, and to several models. None of the models is found to be able to describe simultaneously the shape of transverse momentum spectra, the shape of rapidity distribution and the total yield

NA61/SHINE measurements of anisotropic flow relative to the spectator plane in Pb+Pb collisions at 30A GeV/c

We present an analysis of the anisotropic flow harmonics in Pb+Pb collisions at beam momenta of 30A GeV/c collected by the NA61/SHINE experiment in the year 2016. Directed and elliptic flow coefficients are measured relative to the spectator plane estimated with the Projectile Spectators Detector (PSD). The flow coefficients are reported as a function of transverse momentum in different classes of collision centrality. The results are compared with a new analysis of the NA49 data for Pb+Pb collisions at 40A GeV using forward calorimeters (VCal and RCal) for event plane estimation

Search for the critical point by the NA61/SHINE experiment

NA61/SHINE is a fixed target experiment operating at CERN SPS. Its main goals are to search for the critical point of stronglyinteractingmatterandtostudytheonsetofdeconfinement. Forthesegoalsascanofthetwodimensionalphase diagram (T-μB) is being performed at the SPS by measurements of hadron production in proton-proton, proton-nucleus and nucleus-nucleus interactions as a function of collision energy. In this paper the status of the search for the critical point of strongly interacting matter by the NA61/SHINE Collaboration is presented including recent results on proton intermittency, strongly intensive fluctuation observables of multiplicity and transverse momentum fluctuations. These measurements are expected to be sensitive to the correlation length and, therefore, have the ability to reveal the existence of the critical point via possible non-monotonic behavior. The new NA61/SHINE results are compared to the model predictions

2019 ESC/EAS guidelines for the management of dyslipidaemias : Lipid modification to reduce cardiovascular risk

Correction: Volume: 292 Pages: 160-162 DOI: 10.1016/j.atherosclerosis.2019.11.020 Published: JAN 2020Peer reviewe

Two-particle correlations in azimuthal angle and pseudorapidity in inelastic p + p interactions at the CERN Super Proton Synchrotron

Results on two-particle ΔηΔϕ correlations in inelastic p + p interactions at 20, 31, 40, 80, and 158 GeV/c are presented. The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN Super Proton Synchrotron. The data show structures which can be attributed mainly to effects of resonance decays, momentum conservation, and quantum statistics. The results are compared with the Epos and UrQMD models.ISSN:1434-6044ISSN:1434-605