Improving indoor thermal comfort, air quality and the health of older adults through environmental policies in London

In this work we evaluate the potential of selected environmental strategies in reducing air pollution and summertime indoor overheating. Associated changes in mortality rates are also calculated for older adults in London. Reducing these risks for vulnerable groups is an immediate priority and given that seniors spend most of their time indoors, our focus is on strategies that prioritize the transformation of residential environments for indoor thermal comfort and air quality improvements. For each strategy, we develop specific scenarios related to building adaptations and test potential reductions on indoor overheating and pollutant exposures from outdoor sources (PM2.5), as well as on senior mortality through the CRAFT tool (Cities Rapid Assessment Framework for Transformation). We then pick the scenarios with highest impacts on mortality, aiming to formulate effective policy recommendations for Greater London. Preliminary results suggest that environmental policies related to the installation of shading could have the highest reduction in heat and pollution-related senior mortality, followed by moderate effects due to building insulation retrofits and the greening of roofs. With an increasing ageing population in the UK and beyond, our work highlights the need for city-level policies to address building modifications, considering the importance of indoor spaces for older adults

Chitosan as a rainfastness adjuvant for agrochemicals

Chitosan has been identified as an excellent rainfastness aid for a model agrochemical. We use fluorescent labelling and microscopy to show that chitosan deposits on Vicia faba leaves are able to resist wash off by rain, both in a lab-scale test and via simulated rain. Furthermore, via the same methods it has been demonstrated that the rainfastness of azoxystrobin, a common fungicide which is fluorescently active, can be improved by formulating with chitosan. These findings via fluorescent microscopy were in agreement with a quantitative LC-MS/MS method in which the exact quantity of active ingredient on a leaf surface was determined before and after a rain wash. The potential of chitosan as a rainfastness aid is further supported by positive comparison with a commercial tank-mix standard, with almost 100% retention of the model active ingredient achieved in both cases after 1 hour of washing with 10 mm h−1 intensity rain

Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis.

BackgroundAtopic dermatitis (AD) is a common skin disorder characterized by chronic inflammation, altered skin barrier function, and inflammatory cell skin infiltration that decreases health-related quality of life (HRQoL). The study objective was to understand the patient perspective of AD burden and determine suitable patient-reported outcome (PRO) measures.MethodsThis mixed methods study involved the collection of qualitative and quantitative information from adults (≥ 18 years old) and adolescents (12 - 17 years old) with clinician-confirmed AD regarding their experiences of AD symptoms and its impact on HRQoL. The first part of the study included three stages: in-person concept elicitation (CE) interviews, a 2-week daily electronic diary (eDiary) study, and in-person cognitive debriefing (CD) interviews. An Itch numeric rating scale (NRS) (v1.0) and a Skin Pain NRS (v1.0) evaluation during CD interviews required participants to think about their 'worst' itch and 'worst' skin pain in the past 24 h. Other PRO measures allowed for psychometric testing. The second part of the study involved telephone-depth interviews (TDIs) and qualitative feedback from participants who had not participated in the CD interviews. Qualitative data were thematically analyzed. Psychometric evaluation of NRS measures was performed using eDiary data.ResultsIn the CE interviews, itch and/or itching and skin pain were the most prevalent symptoms consistently discussed by participants. Both NRS measures demonstrated strong psychometric reliability and were applicable across ages with suitable concurrent validity. During the CD interviews, some participants focused their answers on their 'average' itch/itching in the past 24 h, rather than their 'worst' itch. Some participants answered the Skin Pain NRS thinking about general pain or other types of pain, rather than skin pain specifically. Consequently, modifications to both measures addressed these issues and re-tested as paper-and-pen versions in subsequent TDIs. Itch NRS (v2.0) modifications helped participants focus on their worst itching. Most participants preferred Skin Pain NRS v2.0b, which included skin pain descriptors.ConclusionsItching and skin pain are the most important and relevant AD symptoms. The Itch NRS (v2.0) and Skin Pain NRS (v2.0b) appear to be appropriate endpoints for the assessment of itching and skin pain severity for clinical trials with adults and adolescents with AD

Modelling population exposure to high indoor temperatures under changing climates, housing conditions, and urban environments in England

: The exposure of an individual to heat during hot weather depends on several factors including local outdoor temperatures and possible Urban Heat Island (UHI) effects, the thermal performance of the building they inhabit, and any actions that they are able to take in order to modify the indoor thermal conditions. There is an increasing body of research that seeks to understand how housing, UHI, and occupant profiles may alter the risk of mortality during hot weather. Housing overheating models have been of particular interest due to the amount of time spent indoors and the need to improve the energy efficiency of the UK housing stock. A number of housing overheating models have been created in order to understand how changes to the building stock and climate may alter heat exposure and risks of heatrelated mortality. We briefly describe the development of a metamodel – a model derived from the outputs of EnergyPlus dynamic thermal simulation models of building variants – and its application to a housing stock model representative of the West Midlands, UK. We model the stock under a ‘current’ scenario, as described by the 2010-2011 English Housing Survey, and then following a full energy-efficient building fabric retrofit or the installation of external window shutters. Initial results indicate a wide range of overheating risks inside dwelling variants in Birmingham, with flats and bungalows most vulnerable to overheating, and detached dwellings least vulnerable. Modelling of the full retrofit of buildings indicated that the stock would experience an overall increase in overheating, while external shutters were able to decrease overheating significantly

Exercise training in obese rats does not induce browning at thermoneutrality and induces a muscle-like signature in brown adipose tissue

Aim: Exercise training elicits diverse effects on brown (BAT) and white adipose tissue (WAT) physiology in rodents housed below their thermoneutral zone (i.e., 28–32°C). In these conditions, BAT is chronically hyperactive and, unlike human residence, closer to thermoneutrality. Therefore, we set out to determine the effects of exercise training in obese animals at 28°C (i.e., thermoneutrality) on BAT and WAT in its basal (i.e., inactive) state. Methods: Sprague-Dawley rats (n = 12) were housed at thermoneutrality from 3 weeks of age and fed a high-fat diet. At 12 weeks of age half these animals were randomized to 4-weeks of swim-training (1 h/day, 5 days per week). Following a metabolic assessment interscapular and perivascular BAT and inguinal (I)WAT were taken for analysis of thermogenic genes and the proteome. Results: Exercise attenuated weight gain but did not affect total fat mass or thermogenic gene expression. Proteomics revealed an impact of exercise training on 2-oxoglutarate metabolic process, mitochondrial respiratory chain complex IV, carbon metabolism, and oxidative phosphorylation. This was accompanied by an upregulation of multiple proteins involved in skeletal muscle physiology in BAT and an upregulation of muscle specific markers (i.e., Myod1, CkM, Mb, and MyoG). UCP1 mRNA was undetectable in IWAT with proteomics highlighting changes to DNA binding, the positive regulation of apoptosis, HIF-1 signaling and cytokine-cytokine receptor interaction. Conclusion: Exercise training reduced weight gain in obese animals at thermoneutrality and is accompanied by an oxidative signature in BAT which is accompanied by a muscle-like signature rather than induction of thermogenic genes. This may represent a new, UCP1-independent pathway through which BAT physiology is regulated by exercise training

Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32 °C instead of 37 °C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process

Developmental trajectories of emotional disengagement from schoolwork and their longitudinal associations in England

This study identified the varied ways in which emotional disengagement from schoolwork typically developed between 14 and 16 years of age, in the Longitudinal Study of Young People in England. Using growth mixture modelling we found eight main trajectories of (dis)engagement, with four trajectories of either increasing or stable emotional disengagement with schoolwork (41% of the sample). Using propensity score matching to create groups balanced on a wide range of covariates at Wave 1, we compared disengaged students to their engaged counterparts to identify the longitudinal effects of disengagement-trajectory membership on behavioural engagement, psychological wellbeing, substance use, career pathways and achievement. Using linear and binary logistic regressions, we established that students in disengagement trajectories developed lower achievement across compulsory secondary school, and participated less in education and more in employment at age 17 years. In young adulthood (age 19–20 years) they were less likely to attend university and more likely to be unemployed. During secondary schooling, they developed higher levels of substance use and poorer psychological wellbeing, which persisted in the year after compulsory school. However, in young adulthood, the differences in substance use dissipated and students in most of the disengagement trajectories had relatively similar life satisfaction to their counterparts. These findings suggest that students (except perhaps those who became unemployed) were able to develop healthily and happily after leaving the schoolwork environments from which they were emotionally disengaged

Live simultaneous monitoring of mineral deposition and lipid accumulation in differentiating stem cells

Mesenchymal stem cells (MSCs) are progenitors for bone-forming osteoblasts and lipid-storing adipocytes, two major lineages co-existing in bone marrow. When isolated in vitro, these stem cells recapitulate osteoblast or adipocyte formation if treated with specialised media,modelling how these lineages interact in vivo. Osteogenic differentiation is characterised by mineral deposits accumulating in the extracellular matrix, typically assessed using histological techniques. Adipogenesis occurs with accumulation of intracellular lipids that can be routinely visualised by Oil Red O staining. In both cases, staining requires cell fixation and is thus limited to end-point assessments. Here, a vital staining approach was developed to simultaneously detect mineral deposits and lipid droplets in differentiating cultures. Stem cells induced to differentiate produced mixed cultures containing adipocytes and bone-like nodules, and after two weeks live cultures were incubated with tetracycline hydrochloride and Bodipy to label mineral- and lipid-containing structures, respectively. Fluorescence microscopy showed the simultaneous visualisation of mineralised areas and lipid-filled adipocytes in live cultures. Combined with the nuclear stain Hoechst 33258, this approach further enabled live confocal imaging of adipogenic cells interspersed within the mineralised matrix. This multiplex labelling was repeated at subsequent time-points, demonstrating the potential of this new approach for the real-time high-precision imaging of live stem cells

Indoor Air Quality and Overheating in UK Classrooms – an Archetype Stock Modelling Approach

Children spend a large part of their waking lives in school buildings. There is substantial evidence that poor indoor air quality (IAQ) and thermal discomfort can have detrimental impacts on the performance, wellbeing and health of schoolchildren and staff. Maintaining good IAQ while avoiding overheating in classrooms is challenging due to the unique occupancy patterns and heat properties of schools. Building stock modelling has been extensively used in recent years to quantify and evaluate performance of large numbers of buildings at various scales. This paper builds on an archetype stock modelling approach which represents the diversity of the school stock in England through an analysis of The Property Data Survey Programme (PDSP) and the Display Energy Certificates (DEC) databases. The model was used for simulating Indoor-to-Outdoor pollution ratios to estimate indoor air pollution levels (NO2, PM2.5 and CO2) and thermal comfort (overheating) in two climate areas in England: London and the West Pennines. analysis highlighted variations in classrooms' indoor CO2 levels in different seasons and explored the risk of overheating in relation to a classroom's orientation

CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase

In most organisms, telomeres attach to the nuclear envelope at the onset of meiosis to promote the crucial processes of pairing, recombination and synapsis during prophase I. This attachment of meiotic telomeres is mediated by the specific distribution of several nuclear envelope components that interact with the attachment plates of the synaptonemal complex. We have determined by immunofluorescence and electron microscopy that the ablation of the kinase CDK2 alters the nuclear envelope in mouse spermatocytes, and that the proteins SUN1, KASH5 (also known as CCDC155) and lamin C2 show an abnormal cap-like distribution facing the centrosome. Strikingly, some telomeres are not attached to the nuclear envelope but remain at the nuclear interior where they are associated with SUN1 and with nuclear-envelope-detached vesicles. We also demonstrate that mouse testis CDK2 phosphorylates SUN1 in vitro. We propose that during mammalian prophase I the kinase CDK2 is a key factor governing the structure of the nuclear envelope and the telomere-led chromosome movements essential for homolog pairin