Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy

Patients with diabetes type 2 have an increased risk for cardiovascular disease and commonly use combination therapy consisting of the anti-diabetic drug metformin and a cholesterol-lowering statin. However, both drugs act on glucose and lipid metabolism which could lead to adverse effects when used in combination as compared to monotherapy. In this review, the proposed molecular mechanisms of action of statin and metformin therapy in patients with diabetes and dyslipidemia are critically assessed, and a hypothesis for mechanisms underlying interactions between these drugs in combination therapy is developed

High practice variation in risk stratification, baseline oncological staging, and follow-up strategies for T1 colorectal cancers in the Netherlands

Background and study aims Based on pathology, locally resected T1 colorectal cancer (T1-CRC) can be classified as having low- or high-risk for irradicality and/or lymph node metastasis, the latter requiring adjuvant surgery. Reporting and application of pathological high-risk criteria is likely variable, with inherited variation regarding baseline oncological staging, treatment and surveillance. Methods We assessed practice variation using an online survey among gastroenterologists and surgeons participating in the Dutch T1-CRC Working Group. Results Of the 130 invited physicians, 53 % participated. Regardi

Experimental determination of the quasi-particle decay length ξSm\xi_{\text{Sm}} in a superconducting quantum well

We have investigated experimentally the electronic transport properties of a two-dimensional electron gas (2DEG) present in an AlSb/InAs/AlSb quantum well, where part of the toplayer has been replaced by a superconducting Nb strip, with an energy gap $\Delta_0$. By measuring the lateral electronic transport underneath the superconductor, and comparing the experimental results with a model based on the Bogoliubov-de Gennes equation and the Landauer-B\"uttiker formalism, we obtain a decay length $\xi_{\text{Sm}} \approx 100~\text{nm}$ for electrons. This decay length corresponds to an interface transparency $T_{\text{SIN}}=0.7$ between the Nb and InAs. Using this value, we infer an energy gap in the excitation spectrum of the SQW of $\Delta_{\text{eff}} = 0.97 \Delta_0 = 0.83~\text{meV}$.Comment: Revtex, 3 PostScript figure

Short Musculoskeletal Function Assessment:normative data of the Dutch population

The Short Musculoskeletal Function Assessment (SMFA) is widely used in both research and clinical practice. Despite its frequent use, normative data of the SMFA have remained limited. Aim of this study was to gather normative data for the Dutch SMFA (SMFA-NL). The SMFA-NL consists of two indices (function index and bother index) and four subscales (upper extremity dysfunction, lower extremity dysfunction, mental and emotional problems, and problems with daily activities). A total of 900 patients were invited to fill in the SMFA-NL. Six age groups (18-24, 25-34, 35-44, 45-54, 55-64, and 65-75 years) were constructed. Analysis of variance, t tests, and regression analyses were used to assess age and gender effects. The response rate was 97 %. There was a significant difference between men and women in scores on all indices and subscales (range p <0.001 to p = 0.002), except for the upper extremity dysfunction subscale (p = 0.06). A significant interaction effect was found between gender and age for the upper extremity dysfunction subscale; a larger decrease in score with increasing age was observed for women, compared with men. Significant differences were found between age groups for the bother index (p <0.001), lower extremity dysfunction subscale (p = 0.001), and the problems with daily activities subscale (p = 0.002). Significant differences in SMFA-NL scores were found between men and women and between different age groups. These SMFA-NL normative data provide an opportunity of benchmarking health status of participants with musculoskeletal disorders or injuries against their age- and gender-matched peers in the Dutch population

Nilpotent orbits and codimension-two defects of 6d N=(2,0) theories

We study the local properties of a class of codimension-2 defects of the 6d N=(2,0) theories of type J=A,D,E labeled by nilpotent orbits of a Lie algebra \mathfrak{g}, where \mathfrak{g} is determined by J and the outer-automorphism twist around the defect. This class is a natural generalisation of the defects of the 6d theory of type SU(N) labeled by a Young diagram with N boxes. For any of these defects, we determine its contribution to the dimension of the Higgs branch, to the Coulomb branch operators and their scaling dimensions, to the 4d central charges a and c, and to the flavour central charge k.Comment: 57 pages, LaTeX2

Crystalline Assemblies and Densest Packings of a Family of Truncated Tetrahedra and the Role of Directional Entropic Forces

Polyhedra and their arrangements have intrigued humankind since the ancient Greeks and are today important motifs in condensed matter, with application to many classes of liquids and solids. Yet, little is known about the thermodynamically stable phases of polyhedrally-shaped building blocks, such as faceted nanoparticles and colloids. Although hard particles are known to organize due to entropy alone, and some unusual phases are reported in the literature, the role of entropic forces in connection with polyhedral shape is not well understood. Here, we study thermodynamic self-assembly of a family of truncated tetrahedra and report several atomic crystal isostructures, including diamond, {\beta}-tin, and high- pressure lithium, as the polyhedron shape varies from tetrahedral to octahedral. We compare our findings with the densest packings of the truncated tetrahedron family obtained by numerical compression and report a new space filling polyhedron, which has been overlooked in previous searches. Interestingly, the self-assembled structures differ from the densest packings. We show that the self-assembled crystal structures can be understood as a tendency for polyhedra to maximize face-to-face alignment, which can be generalized as directional entropic forces.Comment: Article + supplementary information. 23 pages, 10 figures, 2 table

Oxygen Moment Formation and Canting in Li2CuO2

The possibilities of oxygen moment formation and canting in the quasi-1D cuprate Li2CuO2 are investigated using single crystal neutron diffraction at 2 K. The observed magnetic intensities could not be explained without the inclusion of a large ordered oxygen moment of 0.11(1) Bohr magnetons. Least-squares refinement of the magnetic structure of Li2CuO2 in combination with a spin-density Patterson analysis shows that the magnetization densities of the Cu and O atoms are highly aspherical, forming quasi-1D ribbons of localised Cu and O moments. Magnetic structure refinements and low-field magnetization measurements both suggest that the magnetic structure of Li2CuO2 at 2 K may be canted. A possible model for the canted configuration is proposed.Comment: 10 pages, 8 figures (screen resolution

Measurement of mechanical vibrations excited in aluminium resonators by 0.6 GeV electrons

We present measurements of mechanical vibrations induced by 0.6 GeV electrons impinging on cylindrical and spherical aluminium resonators. To monitor the amplitude of the resonator's vibrational modes we used piezoelectric ceramic sensors, calibrated by standard accelerometers. Calculations using the thermo-acoustic conversion model, agree well with the experimental data, as demonstrated by the specific variation of the excitation strengths with the absorbed energy, and with the traversing particles' track positions. For the first longitudinal mode of the cylindrical resonator we measured a conversion factor of 7.4 +- 1.4 nm/J, confirming the model value of 10 nm/J. Also, for the spherical resonator, we found the model values for the L=2 and L=1 mode amplitudes to be consistent with our measurement. We thus have confirmed the applicability of the model, and we note that calculations based on the model have shown that next generation resonant mass gravitational wave detectors can only be expected to reach their intended ultra high sensitivity if they will be shielded by an appreciable amount of rock, where a veto detector can reduce the background of remaining impinging cosmic rays effectively.Comment: Tex-Article with epsfile, 34 pages including 13 figures and 5 tables. To be published in Rev. Scient. Instr., May 200

Reply to Letter to the Editor HEP-20-0593

We sincerely thank Dr. Javitt for his interest in and perspective on our paper (1). He indicates that aspecific effects of Myrcludex B should be considered an explanation for increased biliary cholesterol and phospholipid secretion after Myrcludex B treatment as partial hepatectomy (PH) also leads to an increased contribution of pericentral hepatocytes to bile salt uptake and secretion but biliary cholesterol and phospholipid secretion are not affected. In our opinion, non-specific Myrcludex B-induced activation of canalicular or sinusoidal transporters seems unlikely given the absence of NTCP homology with these transporters and our data from experiments with SR-B1 or ABCG8 null mice. Myrcludex B is an NTCP-specific peptide showing minimal uptake by hepatocytes

Performance and efficacy of 320-row computed tomography coronary angiography in patients presenting with acute chest pain: results from a clinical registry

The purpose of this study was to evaluate the performance of 320-row computed tomography angiography (CTA) in the identification of significant coronary artery disease (CAD) in patients presenting with acute chest pain and to examine the relation to outcome during follow-up. A total of 106 patients with acute chest pain underwent CTA to evaluate presence of CAD. Each CTA was classified as: normal, non-significant CAD (<50% luminal narrowing) and significant CAD (≥50% luminal narrowing). CTA results were compared with quantitative coronary angiography. After discharge, the following cardiovascular events were recorded: cardiac death, non-fatal infarction, and unstable angina requiring revascularization. Among the 106 patients, 23 patients (22%) had a normal CTA, 19 patients (18%) had non-significant CAD on CTA, 59 patients (55%) had significant CAD on CTA, and 5 patients (5%) had non-diagnostic image quality. In total, 16 patients (15%) were immediately discharged after normal CTA and 90 patients (85%) underwent invasive coronary angiography. Sensitivity, specificity, and positive and negative predictive values to detect significant CAD on CTA were 100, 87, 93, and 100%, respectively. During mean follow-up of 13.7 months, no cardiovascular events occurred in patients with a normal CTA examination. In patients with non-significant CAD on CTA, no cardiac death or myocardial infarctions occurred and only 1 patient underwent revascularization due to unstable angina. In patients presenting with acute chest pain, an excellent clinical performance for the non-invasive assessment of significant CAD was demonstrated using CTA. Importantly, normal or non-significant CAD on CTA predicted a low rate of adverse cardiovascular events and favorable outcome during follow-up