Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy

Premature ovarian insufficiency (POI) – the loss of ovarian function before the age of 40 years, a decade before natural menopause – is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women’s decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI

Electromagnetic Actuated stirring in Microbioreactors enabling easier multiplexing & flexible device design

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The development of a novel electromagnetically (EM) actuated stirring method, for use in microbioreactors, is reported. Mixing in microbioreactors is critical to ensure even distribution of nutrients to microorganisms and cells. Magnetically driven stirrer bars or peristaltic mixing are the most commonly utilised mixing methods employed in completely liquid-filled microbioreactors. However the circular reactor shape required for mixing with a stirrer bar and frequently used for peristaltically mixed microbioreactors presents difficulties for bubble-free priming in a microfluidic bioreactor. Moreover the circular shape and the hardware required for both types of mixing reduces the potential packing density of multiplexed reactors. We present a new method of mixing, displaying design flexibility by demonstrating mixing in circular and diamond-shaped reactors and a duplex diamond reactor and fermentation of the gram-positive bacteria S. carnosus in a diamond-shaped microbioreactor system. The results of the optimisation of this mixing method for performing fermentations alongside both batch and continuous culture fermentations are presented

Engaging political histories of urban uprisings with young people: The Liverpool riots, 1981 and 2011

Based on a participatory research project which involved academics and young people at KCC Live, a community radio station in Merseyside, exploring the 1981 and 2011 riots in Liverpool, UK, this paper argues that co-produced research involving young people and radio provides an under-utilised avenue for research on historical and political geographies. Working together for a year in 2012–13, the academic and non-academic participants produced a radio documentary exploring how and why the 1981 riots in Liverpool occurred, and what we could learn from those historical events to help understand the more recent 2011 riots. Young people’s capacities to engage with past events that took place before they were born, in order to reflect on and understand the political present, are seldom explored in research. The research that this paper is based on therefore provides an original and significant contribution to debates on conducting research with young people, in particular developing approaches to thinking through how young people engage with, and make sense of, politics and political activity, especially disruptive or insurgent activities like riots/urban uprisings. As a result, the paper makes an important contribution to work being done on the political capacities of young people; collective histories and memories in young people’s understandings of politics, place, and space; and knowledges of urban uprisings. We argue that bringing children’s/youth geographies into dialogue with political and historical geographies such as those discussed here is a useful avenue for future research. © The Author(s) 2020

Computationally Modelling Cholesterol Metabolism and Atherosclerosis

Cardiovascular disease (CVD) is the leading cause of death globally. The underlying pathological driver of CVD is atherosclerosis. The primary risk factor for atherosclerosis is elevated low-density lipoprotein cholesterol (LDL-C). Dysregulation of cholesterol metabolism is synonymous with a rise in LDL-C. Due to the complexity of cholesterol metabolism and atherosclerosis mathematical models are routinely used to explore their non-trivial dynamics. Mathematical modelling has generated a wealth of useful biological insights, which have deepened our understanding of these processes. To date however, no model has been developed which fully captures how whole-body cholesterol metabolism intersects with atherosclerosis. The main reason for this is one of scale. Whole body cholesterol metabolism is defined by macroscale physiological processes, while atherosclerosis operates mainly at a microscale. This work describes how a model of cholesterol metabolism was combined with a model of atherosclerotic plaque formation. This new model is capable of reproducing the output from its parent models. Using the new model, we demonstrate how this system can be utilized to identify interventions that lower LDL-C and abrogate plaque formation

Further development of an in vitro model for studying the penetration of chemicals through compromised skin

A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24 h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired

Characterization traffic induced compaction in controlled traffic farming (CTF) and random traffic farming (RTF) - A multivariate approach

A field scale experiment was carried out in Pukekohe in 2020 under an annual grass crop season to characterize the subsoil compaction in controlled traffic farming (CTF) and random traffic farming systems (RTF). Soil penetration resistance (PR) measurements were taken in each field using a cone penetrometer fitted with a 100 mm2 60° top angle cone. Multivariate analysis was performed to identify penetration resistance by depth through cluster analysis and principal component analysis (PCA). Repeated measures ANOVA was performed on the penetration data using the mixed model procedure to determine the treatment effects. In RTF, the penetrometer values increased more rapidly with depth resulting in higher values being recorded from 20cm compared to CTF. In contrast, it was greater in CTF than in RTF at the subsurface (55-60cm). The differences in PR declined beyond 55cm depth at both sites. All depths showed that differences in soil PR were most apparent in the 5-40cm depth, with significant differences between CTF and RTF (P0.05) showing that the soil layers were homogeneous in both systems beyond 40cm depth. The propagation of subsurface compaction was identified at the deeper layer (40-60cm) in CTF systems whereas it was identified from shallower depths (25-55cm) in RTF system

Field-enhanced direct tunneling in ultrathin atomic-layer-deposition-grown Au-Al2O3-Cr metal-insulator-metal structures

Metal-insulator-metal structures based on ultrathin high-k dielectric films are underpinning a rapidly increasing number of devices and applications. Here, we report detailed electrical characterizations of asymmetric metal-insulator-metal devices featuring atomic layer deposited 2-nm-thick Al2O3 films. We find a high consistency in the current density as a function of applied electric field between devices with very different surface areas and significant asymmetries in the IV characteristics. We show by TEM that the thickness of the dielectric film and the quality of the metal-insulator interfaces are highly uniform and of high quality, respectively. In addition, we develop a model which accounts for the field enhancement due to the small sharp features on the electrode surface and show that this can very accurately describe the observed asymmetry in the current-voltage characteristic, which cannot be explained by the difference in work function alone

Seasonal Variation of the Hydro-Environmental Factors and Phytoplankton Community around Waters in Tincan Island, Lagos State, Nigeria

The phytoplankton diversity, pigment, abundance and distribution in relation to physico-chemical parameters were studied from four stations for a period of five months (May \u2013 September 2018) and were analysed using standard procedures. Rainfall was highest (329.5 mm) in September and lowest (142.7 mm) in July. The total suspended solid (TSS) had a mean value of 63.10\ub112.81 mg/L and the total dissolved solids (TDS) had the highest value of 15189 mg/L in May which was not significantly different around the sampling points {P > 0.05}. The pH and nitrate level recorded had a mean value of 7.25\ub10.33 and 3.11\ub11.33 mg/L respectively. Microscopic identification revealed a total of 129 species belonging to 62 genera, 22 families and five divisions in the following order of specie abundance: Bacillariophyceae (65 taxa) > Cyanophyceae (27 taxa) > Chlorophyta (20 taxa) > Dinophyceae (10 taxa) > Euglenophyceae (7 taxa). The high dominance of Microcystis aeruginosa observed was indicative of organic pollution. The range of community structure indices were as follows: Margalef Index (0.1406 \u2013 5.295) and Shannon \u2013 Weiner Index (0.02644 - 0.4979). The relatively high nutrient status favours the high abundance of phytoplankton which is understood to be deleterious to the ecosystem. Municipal wastes must be treated or recycled before discharge and a continuous environmental surveillance is required to maintain the biological integrity of this area