The impact of obesity and fitness on endothelial function in polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a highly prevalent heterogeneous syndrome associated with abdominal obesity, insulin resistance and the metabolic syndrome. This clustering of risk factors could translate into an adverse cardiovascular disease (CVD) risk profile. Endothelial dysfunction, an early barometer of CVD, has been exhibited by women with PCOS; however, it remains unclear whether endothelial dysfunction is independent of CVD risk factors in this population. Exercise training has been found to enhance conduit artery and cutaneous microvessel endothelial function in various populations. Nevertheless, limited research exists regarding the cardiovascular effects of exercise in PCOS, and its impact on endothelial function in conduit arteries and cutaneous microvessels, has not been explored. The primary aim of this thesis was to examine nitric oxide (NO)-mediated endothelial function at different levels of the vascular tree in women with PCOS and to establish whether supervised exercise training induces a therapeutic effect on endothelial function. A systematic review of published studies comparing FMD in PCOS and control women was conducted. Twenty-one published studies were identified for inclusion (pCOS n=908; controls n=566). Differences in FMD between PCOS and controls were synthesised and meta-regressed against BMI and age. The pooled mean FMD was 3.5% lower (95% CI=3.4, 3.7%;

Simulation of Light Antinucleus-Nucleus Interactions

Creations of light anti-nuclei (anti-deuterium, anti-tritium, anti-He3 and anti-He4) are observed by collaborations at the LHC and RHIC accelerators. Some cosmic ray experiments are aimed to find the anti-nuclei in cosmic rays. To support the experimental studies of the anti-nuclei a Monte Carlo simulation of anti-nuclei interactions with matter is implemented in the Geant4 toolkit. The implementation combines practically all known theoretical approaches to the problem of antinucleon-nucleon interactions.Comment: 8 pages, 5 figure

Dysregulation of translation factors EIF2S1, EIF5A and EIF6 in intestinal-type adenocarcinoma (ITAC)

Intestinal-type adenocarcinoma (ITAC) is a rare cancer of the nasal cavity and paranasal sinuses that occurs sporadically or secondary to exposure to occupational hazards, such as wood dust and leather. Eukaryotic translation initiation factors have been described as promising targets for novel cancer treatments in many cancers, but hardly anything is known about these factors in ITAC. Here we performed in silico analyses, evaluated the protein levels of EIF2S1, EIF5A and EIF6 in tumour samples and non-neoplastic tissue controls obtained from 145 patients, and correlated these results with clinical outcome data, including tumour site, stage, adjuvant radiotherapy and survival. In silico analyses revealed significant upregulation of the translation factors EIF6 (ITGB4BP), EIF5, EIF2S1 and EIF2S2 (p < 0.05) with a higher arithmetic mean expression in ITAC compared to non-neoplastic tissue (NNT). Immunohistochemical analyses using antibodies against EIF2S1 and EIF6 confirmed a significantly different expression at the protein level (p < 0.05). In conclusion, this work identifies the eukaryotic translation initiation factors EIF2S1 and EIF6 to be significantly upregulated in ITAC. As these factors have been described as promising therapeutic targets in other cancers, this work identifies candidate therapeutic targets in this rare but often deadly cancer

Hadronic Vacuum Polarization and the Lamb Shift

Recent improvements in the determination of the running of the fine-structure constant also allow an update of the hadronic vacuum-polarization contribution to the Lamb shift. We find a shift of -3.40(7) kHz to the 1S level of hydrogen. We also comment on the contribution of this effect to the determination by elastic electron scattering of the r.m.s. radii of nuclei.Comment: 7 pages, latex, 1 figure -- Submitted to Phys. Rev. A -- epsfig.sty require

Revealing three-dimensional structure of individual colloidal crystal grain by coherent x-ray diffractive imaging

We present results of a coherent x-ray diffractive imaging experiment performed on a single colloidal crystal grain. The full three-dimensional (3D) reciprocal space map measured by an azimuthal rotational scan contained several orders of Bragg reflections together with the coherent interference signal between them. Applying the iterative phase retrieval approach, the 3D structure of the crystal grain was reconstructed and positions of individual colloidal particles were resolved. As a result, an exact stacking sequence of hexagonal close-packed layers including planar and linear defects were identified.Comment: 8 pages, 5 figure

Tomography of a Cryo-immobilized Yeast Cell Using Ptychographic Coherent X-Ray Diffractive Imaging

The structural investigation of noncrystalline, soft biological matter using x-rays is of rapidly increasing interest. Large-scale x-ray sources, such as synchrotrons and x-ray free electron lasers, are becoming ever brighter and make the study of such weakly scattering materials more feasible. Variants of coherent diffractive imaging (CDI) are particularly attractive, as the absence of an objective lens between sample and detector ensures that no x-ray photons scattered by a sample are lost in a limited-efficiency imaging system. Furthermore, the reconstructed complex image contains quantitative density information, most directly accessible through its phase, which is proportional to the projected electron density of the sample. If applied in three dimensions, CDI can thus recover the sample's electron density distribution. As the extension to three dimensions is accompanied by a considerable dose applied to the sample, cryogenic cooling is necessary to optimize the structural preservation of a unique sample in the beam. This, however, imposes considerable technical challenges on the experimental realization. Here, we show a route toward the solution of these challenges using ptychographic CDI (PCDI), a scanning variant of coherent imaging. We present an experimental demonstration of the combination of three-dimensional structure determination through PCDI with a cryogenically cooled biological sample—a budding yeast cell (Saccharomyces cerevisiae)—using hard (7.9 keV) synchrotron x-rays. This proof-of-principle demonstration in particular illustrates the potential of PCDI for highly sensitive, quantitative three-dimensional density determination of cryogenically cooled, hydrated, and unstained biological matter and paves the way to future studies of unique, nonreproducible biological cells at higher resolution

Correlation Between the Deuteron Characteristics and the Low-energy Triplet np Scattering Parameters

The correlation relationship between the deuteron asymptotic normalization constant, $A_{S}$, and the triplet np scattering length, $a_{t}$, is investigated. It is found that 99.7% of the asymptotic constant $A_{S}$ is determined by the scattering length $a_{t}$. It is shown that the linear correlation relationship between the quantities $A_{S}^{-2}$ and $1/a_{t}$ provides a good test of correctness of various models of nucleon-nucleon interaction. It is revealed that, for the normalization constant $A_{S}$ and for the root-mean-square deuteron radius $r_{d}$, the results obtained with the experimental value recommended at present for the triplet scattering length $a_{t}$ are exaggerated with respect to their experimental counterparts. By using the latest experimental phase shifts of Arndt et al., we obtain, for the low-energy scattering parameters ($a_{t}$, $r_{t}$, $P_{t}$) and for the deuteron characteristics ($A_{S}$, $r_{d}$), results that comply well with experimental data.Comment: 19 pages, 1 figure, To be published in Physics of Atomic Nucle

Multi-channel analog of the effective-range expansion

Similarly to the standard effective range expansion that is done near the threshold energy, we obtain a generalized power-series expansion of the multi-channel Jost-matrix that can be done near an arbitrary point on the Riemann surface of the energy within the domain of its analyticity. In order to do this, we analytically factorize its momentum dependencies at all the branching points on the Riemann surface. The remaining single-valued matrix functions of the energy are then expanded in the power-series near an arbitrary point in the domain of the complex energy plane where it is analytic. A systematic and accurate procedure has been developed for calculating the expansion coefficients. This means that near an arbitrary point in the domain of physically interesting complex energies it is possible to obtain a semi-analytic expression for the Jost-matrix (and therefore for the S-matrix) and use it, for example, to locate the spectral points (bound and resonant states) as the S-matrix poles.Comment: 33 pages, 10 figure

Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI).

INTRODUCTION: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. METHODS AND ANALYSIS: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function. ETHICAL APPROVAL: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. TRIAL REGISTRATION NUMBERS: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677