How old church records are helping us to assess the impact of childhood disease and why we’re living longer

First paragraph: The Great Exhibition of 1851, housed in London’s Crystal Palace, showcased the newest of culture and science – including the world’s largest diamond, a precursor to the fax machine and barometer which worked entirely through leeches. Living conditions were tough, but having survived to the age of 20, a young Londoner attending the exhibition could expect to live until around 60. A century and a half later, 20-year-old Londoners watching the Olympics down the pub can expect to live to the age of 80. Access this article on The Conversation website: https://theconversation.com/how-old-church-records-are-helping-us-to-assess-the-impact-of-childhood-disease-and-why-were-living-longer-6374

Emulsion Templated Porous Polymers as Scaffolds for 3D Hepatocyte Culture

Hepatocytes are the main functional cells of the liver and are used extensively in vitro for predicting in vivo drug toxicity profiles. However, the predictive accuracy of in vitro hepatocyte models depends on the physiological relevance of the artificial growth environment. Conventional in vitro hepatocyte models have employed monolayer cultures on two-dimensional (2D) substrates, forcing cells into a flattened morphology that is far removed from the in vivo scenario. Unsurprisingly, 2D cultures often show significant deviations from native liver genotype and phenotype and so are unable to accurately predict drug toxicity. Accordingly, it is hypothesised that approximating the native liver three-dimensional (3D) tissue architecture in vitro will help to preserve genotype and phenotype and so improve predictive accuracy. In this study, emulsion templated porous polymers were investigated as scaffolds for 3D hepatocyte culture. In particular, porous polystyrene scaffolds were explored due to their high porosity, reproducibility and suitable mechanical strength properties. Hepatocytes were cultured on polystyrene scaffolds under a range of culture conditions and were found to approximate native liver density and architecture. The morphology of hepatocytes in scaffolds was representative of in vivo, unlike the flattened morphology of 2D cultures. Crucial ultrastructural features involved in drug detoxification such as bile canaliculi were also present in scaffold cultures, but almost absent from 2D cultures. Importantly, these representative structural features translated into functional and genetic improvements in vitro. Hepatocytes in scaffolds displayed increased albumin synthesis, a key marker of hepatocyte function. Hepatic cell lines also showed increased resistance to drug toxicity compared to 2D cultures. Hepatic drug metabolising genotype was also increased to more physiologically relevant levels in scaffolds compared to 2D cultures. In addition, emulsion templated polystyrene scaffolds were also made more biochemically relevant by surface functionalising with galactose, a ligand known to selectively bind to hepatocytes in vivo via the asialoglycoprotein receptor (ASGP-R). Scaffold morphology was maintained with the incorporation of galactose, allowing cells to approximate native liver tissue architecture. Moreover, the pendent galactose ligands were found to be accessible to hepatocytes adhering onto the scaffold. In summary, this thesis has shown that emulsion templated porous polymers can offer a more physiologically relevant growth environment for hepatocytes in vitro. This could have a profound effect on improving drug toxicity predictions and so reducing the dependence on animal testing

Social and economic effects of spatial distribution in island communities: Comparing the Isles of Scilly and Isle of Wight, UK

AbstractThere has been increasing awareness that communities based on islands are subject to particular island-related factors (the so-called ‘island effect’). This paper sheds empirical light on how the island effect differs in different kinds of island communities, specifically solitary islands on the one hand and archipelagos on the other. It does so by comparing two subnational island jurisdictions (SNIJs) in England: the Isles of Scilly and the Isle of Wight. By analysing census statistics, we show how the spatial distribution in the Isles of Scilly (an archipelago) and the Isle of Wight (a solitary island) is interrelated with patterns of population and employment. Although the Isles of Scilly and the Isle of Wight are both tourism economies, the data indicates that, in social and economic terms, the Isles of Scilly benefits while the Isle of Wight suffers as a result of their different patterns of spatial distribution. We conclude that an island community’s spatial distribution has a significant influence on its societal development and that the island effect differs among islands with different patterns of spatial distribution

Testing the evolutionary basis of the Predictive Adaptive Response hypothesis in a preindustrial human population

Background and objectives: The thrifty phenotype hypothesis proposes that late-life metabolic diseases result from mismatch between early-life and adulthood nutrition. More recently, the predictive adaptive response (PAR) hypothesis has suggested that poor early-life environmental conditions induce metabolic changes which maximise health and fitness in similarly poor adult conditions, but reduce fitness if conditions later improve. Therefore later-life survival and reproduction should be maximised where environmental conditions during development and adulthood match, but few studies in humans have addressed the consequences of poor early conditions on fitness traits in varying later conditions. Methodology: We tested key evolutionary predictions of the PAR hypothesis using detailed longitudinal data with several environmental parameters from a natural fertility preindustrial human population, to investigate how combinations of early- and late-life environmental conditions affected annual probabilities of survival and reproduction. Results: We found no suggestion that fitness was maximised when developmental and later-life conditions matched, but rather poor environmental conditions during development or later life and their combination were associated with lower survival. Conclusions and implications: Our results are more consistent with predictions of ‘silver spoon’ models, whereby adverse early-life conditions are detrimental to later health and fitness across all environments. Future evolutionary research on understanding metabolic disease epidemiology should focus on determining whether adaptive prediction maximises infant survival where conditions match during development and immediately after birth, rather than drawing attention to the unlikely long-term fitness benefits of putative metabolic changes associated with poor early nutrition

Parasites and life history variation in a wild mammal

The purpose of this thesis is to investigate associations between parasite infection and host life-history variation in the wild Soay sheep population of the islands of St Kilda, NW Scotland. Studying host-parasite interactions in wild animal populations is of interest because of the importance of heterogeneity in resource availability, genetics, and environmental conditions in determining resistance to parasites, with implications for human populations and wildlife conservation and management. However, very few studies are able to investigate these associations in a longitudinal manner, which is essential in order to understand how infection is associated with life-history variation across ages and environmental conditions. In this thesis, I investigate associations between parasite resistance and ageing and the importance of maternal effects on offspring parasite resistance. I also establish the shape of natural selection on parasite resistance, and associations between measures of parasite burden and antibody responses. The principle findings of the analyses presented in this thesis are: i) Adult sheep of both sexes show a decline in parasite resistance in old age which is consistent with senescence. Furthermore, the rate of decline in parasite resistance with age is accelerated in individuals that have experienced more stressful environmental conditions over their lifespan. ii) Aspects of maternal phenotype and lamb early life performance are significantly associated with parasite resistance in lambs. Some of these effects persist into adult life and may even affect late-life changes in parasite resistance with age. iii) Analysis of ageing in five female reproductive traits shows that the contributions of individual senescence, terminal effects, and selective disappearance vary across traits, and that therefore multiple traits should be studied in order to understand ageing more fully. Most strikingly, there was no evidence for significant senescence in the probability of producing twins. iv) The first estimate of the strength of natural selection on parasite resistance in a longitudinally-monitored population provided evidence for positive selection on parasite resistance in lambs but not adults. Selection in lambs also varied across environmental conditions, being stronger in years of more favourable conditions. v) Analysis of associations between estimates of parasite burden and antibody responses showed that an estimate of parasite burden was not correlated with either a general or parasite-specific antibody response. However, antibody responses were positively correlated, and there was some evidence for a genetic correlation between the two in lambs but not adults

Identifying infection in chronic wounds in a community setting: a systematic review of diagnostic test accuracy studies

To determine the diagnostic accuracy of different methods currently available to identify infection in chronic wounds applicable to adult patients in a community setting. Systematic review of diagnostic test accuracy studies. Two authors independently completed screening, data extraction and quality and bias assessments (QUADAS2). Eligible studies compared a method (index test) for detecting infection (diagnosis of interest) with microscopy and culture of either deep tissue biopsy or wound swab (reference test) in adult patients with wounds of >4 weeks duration (participants). The results were synthesized narratively. We systematically searched CINAHL, Embase and Medline from 2011 to April 2022. Four studies were included, all recruiting from secondary care wound clinics. Two studies assessed the diagnostic accuracy of Moleculight i:X, a bacterial fluorescence imaging device against deep tissue biopsy culture. One study assessed the diagnostic accuracy of the elevation of various enzymes detected in wound fluid against wound swab microscopy of culture. One study assessed the diagnostic accuracy of bacterial protease activity against wound swab microscopy and culture. Sensitivities of these methods ranged from 50 to 75% and specificities from 47 to 100%. Only a small number of studies were included in this systematic review due to our strict inclusion criteria. We have not identified any methods for diagnosing infection in chronic wounds with either a sufficient quality of evidence to recommend their use in community settings at present. Further research is needed to develop and evaluate appropriate diagnostics for this purpose. This study highlights the paucity of research into wound diagnostics in a community setting and should prompt further research in this area. Accurate diagnostic tests have the potential to improve community-based wound care by optimizing antibiotic use and potentially improving healing time. PRISMA-DTA checklist. The PPI group for the NIHR Community Healthcare MIC were supportive of this topic of work

Genetic recombination is targeted towards gene promoter regions in dogs

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.Comment: Updated version, with significant revision

Microfiber release from real soiled consumer laundry and the impact of fabric care products and washing conditions

Fiber release during domestic textile washing is a cause of marine microplastic pollution, but better understanding of the magnitude of the issue and role of fabric care products, appliances and washing cycles is needed. Soiled consumer wash loads from U.K. households were found to release a mean of 114 ± 66.8 ppm (mg microfiber per kg fabric) (n = 79) fibers during typical washing conditions and these were mainly composed of natural fibers. Microfiber release decreased with increasing wash load size and hence decreasing water to fabric ratio, with mean microfiber release from wash loads in the mass range 1.0–3.5 kg (n = 57) found to be 132.4 ± 68.6 ppm, significantly (p = 3.3 x 10−8) higher than the 66.3 ± 27.0 ppm of those in the 3.5–6.0 kg range (n = 22). In further tests with similar soiled consumer wash loads, moving to colder and quicker washing cycles (i.e. 15°C for 30 mins, as opposed to 40°C for 85 mins) significantly reduced microfiber generation by 30% (p = 0.036) and reduced whiteness loss by 42% (p = 0.000) through reduced dye transfer and soil re-deposition, compared to conventional 40°C cycles. In multicycle technical testing, detergent pods were selected for investigation and found to have no impact on microfiber release compared to washing in water alone. Fabric softeners were also found to have no direct impact on microfiber release in testing under both European and North American washing conditions. Extended testing of polyester fleece garments up to a 48-wash cycle history under European conditions found that microfiber release significantly reduced to a consistent low level of 28.7 ± 10.9 ppm from eight through 64 washes. Emerging North American High-Efficiency top-loading washing machines generated significantly lower microfiber release than traditional top-loading machines, likely due to their lower water fill volumes and hence lower water to fabric ratio, with a 69.7% reduction observed for polyester fleece (n = 32, p = 7.9 x 10−6) and 37.4% reduction for polyester T-shirt (n = 32, p = 0.0032). These results conclude that consumers can directly reduce the levels of microfibers generated per wash during domestic textile washing by using colder and quicker wash cycles, washing complete (but not overfilled) loads, and (in North America) converting to High-Efficiency washing machines. Moving to colder and quicker cycles will also indirectly reduce microfiber release by extending the lifetime of clothing, leading to fewer new garments being purchased and hence lower incidence of the high microfiber release occurring during the first few washes of a new item

Interrogating the technical, economic and cultural challenges of delivering the PassivHaus standard in the UK.

A peer-reviewed eBook, which is based on a collaborative research project coordinated by Dr. Henrik Schoenefeldt at the Centre for Architecture and Sustainable Environment at the University of Kent between May 2013 and June 2014. This project investigated how architectural practice and the building industry are adapting in order to successfully deliver Passivhaus standard buildings in the UK. Through detailed case studies the project explored the learning process underlying the delivery of fourteen buildings, certified between 2009 and 2013. Largely founded on the study of the original project correspondence and semi-structured interviews with clients, architects, town planners, contractors and manufacturers, these case studies have illuminated the more immediate technical as well as the broader cultural challenges. The peer-reviewers of this book stressed that the findings included in the book are valuable to students, practitioners and academic researchers in the field of low-energy design. It was launched during the PassivHaus Project Conference, held at the Bulb Innovation Centre on the 27th June 2014