Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Assessing the impact of anaemia on stable isotope ratios using the medieval population of Ecija, Spain.

Osteoarchaeology and funerary archaeolog

Intranasal Papilloma: A Suspected Case of Inverted Schneiderian Papilloma in the Choana of Adult Male from Post-Medieval Europe.

During the routine assessment of skeletal material unearthed from Middenbeemster, a post-Medieval (AD 17–19th century) cemetery in Northern Holland, an adult male with an unidentified choanal lesion was discovered. The affected individual was analysed macroscopically and via computer tomography. Based on the phenotypic and radiographic characteristics of the lesion, and after a comprehensive review of clinical literature, it was determined that the lesion was likely caused by an inverted Schneiderian papilloma (ISP), a benign but locally aggressive endophytic neoplasm histopathologically characterized by the inversion of the epithelium into the lamina propria (Schneiderian membrane) of the respiratory nasal mucosa. This study presents a detailed description of the pathophysiology and aetiology of ISPs, using both bioarchaeological and biomedical frameworks. Several differential diagnoses are discussed, with emphasis on the reasons for their rejection as the primary pathogenic mechanism(s). To the best of the authors’ knowledge, this research is the first reported case of ISP within palaeopathology, which highlights the need to consider ISPs whenever slow-growing sinonasal neoplasms are suspected, as well as in cases that exhibit focal rhinitis.Osteoarchaeology and funerary archaeolog

Testing the Sternal Clavicle Ageing Method on a Post‐Medieval Dutch Skeletal Collection

When a new method is produced, it should be assessed for accuracy and reliability before widespread use. A new method by Falys and Prangle for estimating age from degeneration of the sternal end of the clavicle is tested in this paper on an 18th–19th‐century known‐age Dutch population (80 clavicles). Intra‐ and inter‐observer tests (Cohen's kappa) revealed slight to moderate agreement (k = 0.100–0.425 and 0.106–0.534 respectively). However, owing to large age ranges, 87% accuracy was achieved. Methodological improvements are suggested that could help the method further to improve age estimates for the elderly in past populations.Bioarchaeolog

Osteological, Biomolecular and Geochemical Examination of an Early Anglo-Saxon Case of Lepromatous Leprosy

We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21–35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America.Osteoarchaeology and funerary archaeolog

Demand Side Response : Exploring How and Why Users Respond to Signals Aimed at Incentivizing a Shift of Electricity Use in Time

With increased weather-dependent electricity production and electrification at the heart of the ongoing transition away from fossil fuels, peaks in electricity demand are set to increase and become increasingly difficult to meet, which threatens the functioning of the electric power systems that our society depends on. Time-varying electricity rates, which aim to incentivize electricity users to shift their electricity use in time, have been proposed as a key instrument in alleviating grid imbalances and bottlenecks. Previous research has found that users respond to such rates by shifting their electricity use in time, but there is great variability in the observed response between studies that remains unexplained. In other words, it is unclear how and why users respond to time-varying rates, and thus how these so called demand side response policies should be designed to provide the best results. This thesis aims to improve our understanding of how and why (not) time-varying rates work by exploring how users respond to both price and non-price signals that aim to incentivize a shift of electricity use in time, and what motivates, discourages, enables and hinders them to respond. This is done through four separate studies that are carried out in contexts where users have been involuntarily subjected to interventions that aim to incentivize demand side response. Using several novel methods, research designs and understudied empirical contexts, the studies also illustrate how biases that are commonly observed in the literature can be avoided and how intervention effects that often remain overlooked can be captured. The results suggest that users may hold different motives to respond to signals that aim to incentivize a shift of electricity use in time, including non-financial motives such as a care for the environment and a will to meet the expectations of others. The rhythms and schedules of people’s everyday lives are identified as the most important hindrances for people to engage in demand side response. Notably, there is no evident relationship between how much money users may save by responding to a signal and their actual response. Many users do hold expectations of saving money and claim to engage in demand side response as a result of those expectations, but the fact that users are rarely (if ever) informed of whether their expectations are met or not suggests that many users may actually be willing to engage in demand side response with little or no financial reward. However, there is a risk that users who expect to save money may refrain from or stop engaging in demand side response if their expectations are not met, which poses a potential threat to the long-run effectiveness of conventional price-based demand response programs. There is also a risk that users who primarily hold non-financial motives may be discouraged to engage in demand side response if monetary savings is the key selling point of demand response programs. Policymakers, professionals and researchers should explore these risks and alternative policies that address them, particularly policies that may be more appealing to users that hold non-financial motives to engage in demand side response. Doing so will be key to ensure that current and future demand side response policies are cost-efficient and effective, both today and tomorrow