The magistrate and the community: summary proceedings in rural England during the long eighteenth century

The study of how the law worked at a local level in rural communities, and in the role of the rural magistrate at summary level, has been the subject of relatively little attention by historians. More attention has been given to the higher courts, when the majority of plebeian men and women who experienced the law during the long eighteenth century would have done so at summary level. Although some work has been carried out on summary proceedings, this has also tended to focus either on metropolitan records, a small number of sources, or on a specific, limited, number of offences. There has not been a broader study of rural summary proceedings to look at how the role and function of the rural magistrate, how local communities used this level of the criminal justice system, as complainants, defendants and witnesses, and how they negotiated their place in their local community through their involvement with the local magistrate. The research presented here uses the surviving summary notebooks of 13 magistrates working across central and southern England as primary sources, taking both a quantitative and qualitative approach to examine how rural summary proceedings operated. It shows that there was wide participation in the summary process in rural England, and that rural magistrates had a more individualised approach to their summary work and decision-making than their London equivalents. It reveals how even the poorest members of rural societies were able to employ agency and display authority in their appearances before the magistrate, and demonstrates the extent to which the use of discretion, mediation and arbitration were key functions of the rural justice

Phylogenomics and analysis of shared genes suggest a single transition to mutualism in Wolbachia of nematodes

Wolbachia, endosymbiotic bacteria of the order Rickettsiales, are widespread in arthropods but also present in nematodes. In arthropods, A and B supergroup Wolbachia are generally associated with distortion of host reproduction. In filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that C and D supergroup Wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. The origin of this mutualistic endosymbiosis is of interest for both basic and applied reasons: How does a parasite become a mutualist? Could intervention in the mutualism aid in treatment of human disease? Correct rooting and high-quality resolution of Wolbachia relationships are required to resolve this question. However, because of the large genetic distance between Wolbachia and the nearest outgroups, and the limited number of genomes so far available for large-scale analyses, current phylogenies do not provide robust answers. We therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of Litomosoides sigmodontis, revisited the selection of loci for phylogenomic analyses, and performed a phylogenomic analysis including available complete genomes (from isolates in supergroups A, B, C, and D). Using 90 orthologous genes with reliable phylogenetic signals, we obtained a robust phylogenetic reconstruction, including a highly supported root to the Wolbachia phylogeny between a (A + B) clade and a (C + D) clade. Although we currently lack data from several Wolbachia supergroups, notably F, our analysis supports a model wherein the putatively mutualist endosymbiotic relationship between Wolbachia and nematodes originated from a single transition event

Understanding the yeast host cell response to recombinant membrane protein production

Membrane proteins are drug targets for a wide range of diseases. Having access to appropriate samples for further research underpins the pharmaceutical industry's strategy for developing new drugs. This is typically achieved by synthesizing a protein of interest in host cells that can be cultured on a large scale, allowing the isolation of the pure protein in quantities much higher than those found in the protein's native source. Yeast is a popular host as it is a eukaryote with similar synthetic machinery to that of the native human source cells of many proteins of interest, while also being quick, easy and cheap to grow and process. Even in these cells, the production of human membrane proteins can be plagued by low functional yields; we wish to understand why. We have identified molecular mechanisms and culture parameters underpinning high yields and have consolidated our findings to engineer improved yeast host strains. By relieving the bottlenecks to recombinant membrane protein production in yeast, we aim to contribute to the drug discovery pipeline, while providing insight into translational processes

The cost of severe haemophilia in Europe: the CHESS study

Background Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Results Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. Conclusions The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a ‘snapshot’ of information for patients with rare diseases

Emerging variants of canine enteric coronavirus associated with seasonal outbreaks of severe canine gastroenteric disease

Canine enteric coronavirus (CECoV) variants have an emerging role in severe outbreaks of canine gastroenteritis. Here we used syndromic health data from a sentinel network of UK veterinary practices to identify an outbreak of severe canine gastroenteritis. Affected dogs frequently presented with vomiting, diarrhoea and inappetence. Data from sentinel diagnostic laboratories showed similar seasonal increases in CECoV diagnosis. Membrane glycoprotein (M) gene sequence analysis implied wide geographical circulation of a new CECoV variant. Whole genome sequencing suggested the main circulating 2022 variant was most closely related to one previously identified in 2020 with additional spike gene recombination; all variants were unrelated to CECoV-like viruses recently associated with human respiratory disease. Identifying factors that drive population-level evolution, and its implications for host protection and virulence, will be important to understand the emerging role of CECoV variants in canine and human health, and may act as a model for coronavirus population adaptation more widely

Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study

Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making