Properties of Trapped Electrons

The current experimental evidence relating to absorption spectra, spontaneous decay and photo-bleaching of electrons trapped in non-ionic media is reviewed and the present state of the trapped electron theories which have been applied to these systems is discussed. Localised molecular orbital studies are performed on the hydrogen bonding interaction and the results are discussed in relation to present semicontinuum theories. The relevance of photoionisation spectra to trapped electron absorption in ice is investigated by considering the sensitivity of spectral features to well parameters for some simple potentials. The spontaneous short term decay of electrons at low temperature is investigated by means of a tunneling model which incorporates electron-scaven-ger distribution features. Electron-parent cation distributions are also considered and the results discussed in relation to the 'spur' model. A general photobleaching scheme is presented and quantum efficiencies are evaluated for ice and two organic media. In the former the wavelength dependence is reproduced by means of a mobile electron capture model whilst in the latter, bleaching by means of tunneling from long lived excited states is considered

A roadmap to achieve pharmacological precision medicine in diabetes

Current pharmacological treatment of diabetes is largely algorithmic. Other than for cardiovascular disease or renal disease, where sodium–glucose cotransporter 2 inhibitors and/or glucagon-like peptide-1 receptor agonists are indicated, the choice of treatment is based upon overall risks of harm or side effect and cost, and not on probable benefit. Here we argue that a more precise approach to treatment choice is necessary to maximise benefit and minimise harm from existing diabetes therapies. We propose a roadmap to achieve precision medicine as standard of care, to discuss current progress in relation to monogenic diabetes and type 2 diabetes, and to determine what additional work is required. The first step is to identify robust and reliable genetic predictors of response, recognising that genotype is static over time and provides the skeleton upon which modifiers such as clinical phenotype and metabolic biomarkers can be overlaid. The second step is to identify these metabolic biomarkers (e.g. beta cell function, insulin sensitivity, BMI, liver fat, metabolite profile), which capture the metabolic state at the point of prescribing and may have a large impact on drug response. Third, we need to show that predictions that utilise these genetic and metabolic biomarkers improve therapeutic outcomes for patients, and fourth, that this is cost-effective. Finally, these biomarkers and prediction models need to be embedded in clinical care systems to enable effective and equitable clinical implementation. Whilst this roadmap is largely complete for monogenic diabetes, we still have considerable work to do to implement this for type 2 diabetes. Increasing collaborations, including with industry, and access to clinical trial data should enable progress to implementation of precision treatment in type 2 diabetes in the near future. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains a slideset of the figures for download, which is available at 10.1007/s00125-022-05732-3

Effect of reheating on predictions following multiple-field inflation

We study the sensitivity of cosmological observables to the reheating phase following inflation driven by many scalar fields. We describe a method which allows semi-analytic treatment of the impact of perturbative reheating on cosmological perturbations using the sudden decay approximation. Focusing on $\mathcal{N}$-quadratic inflation, we show how the scalar spectral index and tensor-to-scalar ratio are affected by the rates at which the scalar fields decay into radiation. We find that for certain choices of decay rates, reheating following multiple-field inflation can have a significant impact on the prediction of cosmological observables.Comment: Published in PRD. 4 figures, 10 page

Impact of Dietary Energy Source on the Responses of Pigs to an Acute Level of Antigen Exposure

Two trials were conducted to determine the response of pigs experiencing a low or high level of acute antigen exposure to three dietary energy regimens: a low-fat basal diet, basal diet plus 6% added choice white grease (low linoleic acid), and basal diet plus 6% added corn oil (high linoleic acid). All pigs were reared via a segregated early weaning scheme to minimize the pigs’ exposure to environmental antigens and thus level of immune system activation. Three littermate pigs in each of 24 litters were allotted at 21 days to one of the three dietary energy regimens for 37 days. Onehalf of the pigs in each trial were administered lipopolysaccharide (LPS), an acute stimulant of the immune system, on day 21 of the trial and again eight days later. LPS administration resulted in a short-term acute depression in pig performance in both trials. The magnitude and duration of the pigs’ response to LPS differed between trials and thus results are reported separately. Prior to antigen (LPS) administration, dietary fat additions resulted in faster daily gains in trial 1 and greater efficiency of dietary energy (metabolizable energy, ME) utilization in trials 1 and 2. Responses to the two fat sources were similar in both trials. During the period of acute antigen exposure (day 0 to 4 post-LPS), daily weight gain and gain:ME ratios were similar among the three dietary regimens in both AE groups. Following partial antigen clearance from the body (day 4 to 8 post-LPS), dietary additions of either fat source again resulted in faster daily gains in trial 1 and improved gain:ME ratios in trial 2 in both AE groups. Based on these data, dietary additions of fat (both low and high in linoleic acid content) result in greater growth rates and efficiency of dietary ME utilization in pigs both prior to and following a period of acute antigen exposure

Impact of Level of Antigen Exposure on Response of Pigs to Dietary Energy Sources

Two levels of chronic antigen exposure (moderate and high) were created by rearing pigs via a segregated-earlyweaning and a conventional rearing scheme, respectively. In each antigen exposure group, three littermate pigs in each of nine litters were fed one of three energy sources from 13 to 60 pounds body weight. Fifteen percent of the metabolizable energy (ME) content of the diets was provided by corn starch (CS), choice white grease (CWG), or corn oil (CO). Moderate AE pigs consumed more ME per day and grew faster than high AE pigs. The dietary inclusion of fat calories (CWG, CO) for starch calories resulted in greater daily body weight gains and gain:ME ratios in both moderate and high AE pigs. The magnitude of growth responses to the two fat calorie sources was similar in both AE groups. Based on these data, dietary fat calories support greater growth rate and efficiency of dietary ME utilization than starch calories in pigs experiencing either moderate or high levels of antigen exposure

A practical guide for the study of human and murine sebaceous glands in situ

The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid-producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno-)histomorphometric methods for standardised SG evaluation