Fibroblast growth factor 21 in heart failure

Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF

What can we learn from a race with one runner? A comment on Foreman-Peck and Zhou, ‘Late marriage as a contributor to the industrial revolution in England’

Foreman-Peck and Zhou’s claim that late marriage was a major contributor to the Industrial Revolution in England cannot be sustained. They consider neither other influences on English industrialisation nor other European economies where marriage age was high throughout the early modern period but industrialisation came much later. It is not possible to argue that late marriage age was a major contributor to English industrialisation without analysing other possible contributing factors. Any consideration of this question must assess marriage age alongside other causes of industrialisation and explain why other European economies with higher marriage age industrialised much later than England

Including debris cover effects in a distributed model of glacier ablation

Distributed glacier melt models generally assume that the glacier surface consists of bare exposed ice and snow. In reality, many glaciers are wholly or partially covered in layers of debris that tend to suppress ablation rates. In this paper, an existing physically based point model for the ablation of debris-covered ice is incorporated in a distributed melt model and applied to Haut Glacier d’Arolla, Switzerland, which has three large patches of debris cover on its surface. The model is based on a 10 m resolution digital elevation model (DEM) of the area; each glacier pixel in the DEM is defined as either bare or debris-covered ice, and may be covered in snow that must be melted off before ice ablation is assumed to occur. Each debris-covered pixel is assigned a debris thickness value using probability distributions based on over 1000 manual thickness measurements. Locally observed meteorological data are used to run energy balance calculations in every pixel, using an approach suitable for snow, bare ice or debris-covered ice as appropriate. The use of the debris model significantly reduces the total ablation in the debris-covered areas, however the precise reduction is sensitive to the temperature extrapolation used in the model distribution because air near the debris surface tends to be slightly warmer than over bare ice. Overall results suggest that the debris patches, which cover 10% of the glacierized area, reduce total runoff from the glacierized part of the basin by up to 7%

Leftovers:The presence of manufacture-derived aquatic lipids in Alaskan Pottery

Lipids preserved within the walls of ancient pottery vessels are routinely analysed to reveal their original contents. The provenience of aquatic lipids in pottery is generally connected to vessel function (e.g., for cooking or storing fish, shellfish and aquatic mammals). However, ethnographic reports from early historic Alaska mention the use of aquatic oils for waterproofing low-fired pottery. Results of lipid residue studies on Alaskan pottery reflect an exclusive function of pottery to process aquatic resources. However, can one be sure these residues are the product of vessel function and not a remnant of the manufacturing process? The study presents the results of an experiment where the preservation of aquatic lipids during the firing process at different temperatures was measured. It was found that nearly all lipids were removed at firing temperatures of ≥ 400°C. Petrographic analysis of Alaskan pottery samples indicates that firing temperatures were generally &gt; 550°C but &lt; 800°C. The contribution of pre-firing manufacture-derived lipids to samples fired at these temperatures may be regarded as negligible. While the possible presence of aquatic lipids from post-firing surface treatments cannot be excluded, such treatments appear unnecessary for well-fired pottery.</p

Quantum transport in ultracold atoms

Ultracold atoms confined by engineered magnetic or optical potentials are ideal systems for studying phenomena otherwise difficult to realize or probe in the solid state because their atomic interaction strength, number of species, density, and geometry can be independently controlled. This review focuses on quantum transport phenomena in atomic gases that mirror and oftentimes either better elucidate or show fundamental differences with those observed in mesoscopic and nanoscopic systems. We discuss significant progress in performing transport experiments in atomic gases, contrast similarities and differences between transport in cold atoms and in condensed matter systems, and survey inspiring theoretical predictions that are difficult to verify in conventional setups. These results further demonstrate the versatility offered by atomic systems in the study of nonequilibrium phenomena and their promise for novel applications.Comment: 24 pages, 7 figures. A revie

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer

Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Outcomes included quality of life (QoL), function (fitness and upper body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5 weeks PS], mid-intervention [6 months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60) groups. There were significant (p < 0.05) interaction effects on QoL, fitness and fatigue with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side effects between groups. This translational intervention trial, delivered either FtF or Tel, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Screening a phage-display single-chain antibody library for binding to the breast cancer cell line PM-1 an antibody, scFv173, recognising activated leukocyte cell adhesion molecule (ALCAM, CD166) was isolated and its binding profile was characterized. Positive ALCAM immunohistochemical staining of frozen human tumour sections was observed. No ALCAM staining was observed in the majority of tested normal human tissues (nine of ten). Flow cytometry analyses revealed binding to 22 of 26 cancer cell lines of various origins and no binding to normal blood and bone marrow cells. Antibody binding inhibited invasion of the breast cancer cell line MDA-MB-231 by 50% in an in vitro Matrigel-coated membrane invasion assay. Reduced growth of tumours in nude mice was observed in an in vivo model in which the mice were injected subcutaneously with colorectal carcinoma HCT 116 cells and treated with scFv173 when compared to control. In summary, we have characterized a novel fully human scFv antibody recognising ALCAM on cancer cells and in tumour tissues that reduces cancer cell invasion and tumour growth in accordance with the hypothesised role for ALCAM in cell growth and migration control

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente