At-risk serum cholesterol profile at both ends of the nutrition spectrum in West African adults? The Benin study

Low HDL-cholesterol (HDL-C), using as cut-offs 1.03 mmol/L in men and 1.29 mmol/L in women, was observed in more than 25% apparently healthy adults (n = 541) in a cross-sectional study on nutrition transition and cardiometabolic risk factors (CMRF) in Benin, West Africa. Both overweight/obesity (35.3%) and underweight (11.3%) were present, displaying the double burden of malnutrition. We examined in more depth the association of low HDL-C with nutrition and with other CMRF. Metabolic syndrome components were assessed, plus the ratio of total cholesterol (TC)/HDL-C and serum homocysteine. Insulin resistance was based on Homeostasis Model Assessment. We also measured BMI and body composition by bio-impedance. Dietary quality was appraised with two non-consecutive 24 h recalls. Low HDL-C was associated with much higher TC/HDL-C and more abdominal obesity in men and women and with more insulin resistance in women. The rate of low HDL-C was highest (41.9%) among the overweight/obese subjects (BMI ≥ 25), but it also reached 31.1% among the underweight (BMI < 18.5), compared with 17.3% among normal-weight subjects (p < 0.001). Lower dietary micronutrient adequacy, in particular, in vitamins A, B3, B12, zinc and calcium, was associated with low HDL-C when controlling for several confounders. This suggests that at-risk lipoprotein cholesterol may be associated with either underweight or overweight/obesity and with poor micronutrient intake

Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264

Pressure induced structural and dynamical changes in liquid Si. An ab-initio study

The static and dynamic properties of liquid Si at high-pressure have been studied using the orbital free ab-initio molecular dynamics method. Four thermodynamic states at pressures 4, 8, 14 and 23 GPa are considered. The calculated static structure shows qualitative agreement with the available experimental data. We analize the remarkable structural changes occurring between 8 and 14 GPa along with its effect on several dynamic properties.Comment: 10 pages, 11 figures. Accepted for publication in Journal of Physics: Condensed Matte

Unbiasing the density of TTV-characterised sub-Neptunes: Update of the mass-radius relationship of 34 Kepler planets

Transit Timing Variations (TTVs) can provide useful information on compact multi-planetary systems observed by transits, by putting constraints on the masses and eccentricities of the observed planets. This is especially helpful when the host star is not bright enough for radial velocity follow-up. However, in the past decades, numerous works have shown that TTV-characterised planets tend to have a lower densities than RV-characterised planets. Re-analysing 34 Kepler planets in the super-Earth to sub-Neptunes range using the RIVERS approach, we show that at least part of these discrepancies was due to the way transit timings were extracted from the light curve, which had a tendency to under-estimate the TTV amplitudes. We recover robust mass estimates (i.e. low prior dependency) for 23 of the planets. We compare these planets the RV-characterised population. A large fraction of these previously had a surprisingly low density now occupy a place of the mass-radius diagram much closer to the bulk of the known planets, although a slight shift toward lower densities remains, which could indicate that the compact multi-planetary systems characterised by TTVs are indeed composed of planets which are different from the bulk of the RV-characterised population. These results are especially important for obtaining an unbiased view of the compact multi-planetary systems detected by Kepler, TESS, and the upcoming PLATO mission

Nematicity as a route to a magnetic field-induced spin density wave order; application to the high temperature cuprates

The electronic nematic order characterized by broken rotational symmetry has been suggested to play an important role in the phase diagram of the high temperature cuprates. We study the interplay between the electronic nematic order and a spin density wave order in the presence of a magnetic field. We show that a cooperation of the nematicity and the magnetic field induces a finite coupling between the spin density wave and spin-triplet staggered flux orders. As a consequence of such a coupling, the magnon gap decreases as the magnetic field increases, and it eventually condenses beyond a critical magnetic field leading to a field-induced spin density wave order. Both commensurate and incommensurate orders are studied, and the experimental implications of our findings are discussed.Comment: 5 pages, 3 figure

Systematic review: Defining, diagnosing and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound

Background: Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross-sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri-enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims: To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods: We searched four databases up to 6 January 2024. Two-stage screening was done in duplicate. We assessed risk of bias using QUADAS-2. Results: There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions: This systematic review is the first step for a structured program to develop a stricture IUS index for CD

The Reform of Employee Compensation in China’s Industrial Enterprises

Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise

Using primary sources to produce a microhistory of translation and translators: theoretical and methodological concerns

In descriptive studies, where the source and target texts are the main primary sources (‘primary text products’), ‘extra-textual’ sources are looked at with ‘circumspection’. However, in historical research methodologies they are central. This article examines the use and value of archives, manuscripts and, especially, translator papers, post-hoc accounts and interviews in producing a history of translation and translators. Rather than informing a ‘traditional’ Rankean history of facts and major personalities, the article underlines the potential value of such material in creating a ‘microhistory’, reclaiming the details of the everyday lives and working processes of sometimes little-known or forgotten translators and contextualising them to construct a social and cultural history of translation and translators. Sometimes these sources are housed in collections where translation may not be very visible, which creates problems of location. Examples are given from the autobiography of A. Birse and research on the working papers of Sam Hileman, Andrew Hurley, Bernard Miall and Margaret Sayers Peden