A Study of Universal Severe Acute Respiratory Syndrome Coronavirus 2 RNA Testing Among Residents and Staff in a Large Group of Care Homes in South London.

BACKGROUND: Care homes have experienced a high number of coronavirus disease 2019 (COVID-19)-related deaths among residents since the onset of the pandemic. However, up to May 2020, there has been a lack of information about the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among residents and staff in care homes and limited testing in this setting. METHODS: Combined nose and throat swab testing for SARS-CoV-2 RNA was carried out in 2455 residents and staff across 37 care homes in the London Borough of Bromley across a 3-week period. Results were reported within 24 hours of sample delivery, and data were collected on the presence or absence of symptoms. RESULTS: Overall, the point prevalence of SARS-CoV-2 infection was 6.5%, with a higher rate in residents (9.0%) than in staff (4.7%). A key finding was the high proportion of asymptomatic infection detected in staff (69%) and residents (51%), with evidence of underdetection of symptoms by care home staff. CONCLUSIONS: The high proportion of asymptomatic infection combined with underdetection of symptoms by care home staff indicates that offering a test to all residents and staff in care homes with rapid reporting of results would assist accurate identification of infected individuals, facilitating prompt infection prevention and control action.

Stories of stones and bones: disciplinarity, narrative and practice in British popular prehistory, 1911-1935.

This paper explores how three central figures in the field of British prehistory - Sir Arthur Keith, Sir Grafton Elliot Smith and Louis Leakey - deployed different disciplinary practices and narrative devices in the popular accounts of human bio-cultural evolution that they produced during the early decades of the twentieth century. It shows how they used a variety of strategies, ranging from virtual witness through personal testimony to tactile demonstration, to ground their authority to interpret the increasingly wide range of fossil material available and to answer the bewildering variety of questions that could be asked about them. It investigates the way in which they positioned their own professional expertise in relation to fossil interpretation, particularly with regard to the - sometimes controversial - use they made of concepts, evidence and practices drawn from other disciplines. In doing so, they made claims that went beyond their original disciplinary boundaries. The paper argues that while none of these writers were able, ultimately, to support the wider claims they made regarding human prehistory, the nature of these claims deserves much closer attention, particularly with respect to the public role that historians of science can and should play in relation to present-day calls for greater interdisciplinarity.

Optimisation of pharmacokinetic properties in a neutral series of 11ß-HSD1 inhibitors.

11ß-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11ß-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution.

A Digital Health Fall Prevention Program for Older Adults: Feasibility Study.

BACKGROUND: About 1 in 3 adults aged 65 and older falls annually. Exercise interventions are effective in reducing the fall risk and fall rate among older adults. In 2020, startup company Age Bold Inc. disseminated the Bold Fall Prevention Program, aiming to reduce falls among older adults through a remotely delivered, digital exercise program. OBJECTIVE: We conducted a feasibility study to assess the delivery of the Bold Fall Prevention Program remotely and evaluate the program's impact on 2 primary outcomes-annualized fall rate and weekly minutes of physical activity (PA)-over 6 months of follow-up. METHODS: Older adults at high risk of falling were screened and recruited for the feasibility study via nationwide digital advertising strategies. Self-reported outcomes were collected via surveys administered at the time of enrollment and after 3 and 6 months. Responses were used to calculate changes in the annualized fall rate and minutes of PA per week. RESULTS: The remote delivery of a progressive digital fall prevention program and associated research study, including remote recruitment, enrollment, and data collection, was deemed feasible. Participants successfully engaged at home with on-demand video exercise classes, self-assessments, and online surveys. We enrolled 65 participants, of whom 48 (74%) were women, and the average participant age was 72.6 years. Of the 65 participants, 54 (83%) took at least 1 exercise class, 40 (62%) responded to at least 1 follow-up survey at either 3 or 6 months, 20 (31%) responded to both follow-up surveys, and 25 (39%) were lost to follow-up. Among all participants who completed at least 1 follow-up survey, weekly minutes of PA increased by 182% (ratio change=2.82, 95% CI 1.26-6.37, n=35) from baseline and annualized falls per year decreased by 46% (incidence rate ratio [IRR]=0.54, 95% CI 0.32-0.90, n=40). Among only 6-month survey responders (n=31, 48%), weekly minutes of PA increased by 206% (ratio change=3.06, 95% CI 1.43-6.55) from baseline to 6 months (n=30, 46%) and the annualized fall rate decreased by 28% (IRR=0.72, 95% CI 0.42-1.23) from baseline to 6 months. CONCLUSIONS: The Bold Fall Prevention Program provides a feasible strategy to increase PA and reduce the burden of falls among older adults.

A place that answers questions: primatological field sites and the making of authentic observations.

The ideals and realities of field research have shaped the development of behavioural primatology over the latter half of the twentieth century. This paper draws on interviews with primatologists as well as a survey of the scientific literature to examine the idealized notion of the field site as a natural place and the physical environment of the field as a research space. It shows that what became standard field practice emerged in the course of wide ranging debate about the techniques, personal qualities and site conditions best suited to the scientific study of the natural behaviour of apes and monkeys. Although the laboratory was a constant presence in this debate, the export of techniques from the laboratory to the field was limited, due to concerns that experimental manipulation would destroy the naturalness of the behaviour. The paper goes on to demonstrate the central significance given by primatologists to the unique social, historical and ecological circumstances of particular field sites, and to sketch some of the complexities that fieldworkers contend with in trying to realize their ideals. Primatologists seek field sites that answer their questions; but once their studies become long term, they also need to find questions that answer to ever changing conditions at those sites.

Novel acidic 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor with reduced acyl glucuronide liability: the discovery of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (AZD8329).

Inhibition of 11ß-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. We report here the optimization of a carboxylic acid class of inhibitors from AZD4017 (1) to the development candidate AZD8329 (27). A structural change from pyridine to pyrazole together with structural optimization led to an improved technical profile in terms of both solubility and pharmacokinetics. The extent of acyl glucuronidation was reduced through structural optimization of both the carboxylic acid and amide substituents, coupled with a reduction in lipophilicity leading to an overall increase in metabolic stability.

Discovery of a potent, selective, and orally bioavailable acidic 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017).

Inhibition of 11ß-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11ß-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.

Structure-based design of protein tyrosine phosphatase-1B inhibitors.

Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template.