Travelling objects: the Wellcome collection in Los Angeles, London and beyond

This paper presents some of my research into the historical medical collection acquired by and on behalf of the pharmaceutical magnate Henry Solomon Wellcome (1853-1936). Specific aims of the paper are to consider how historico-geographical factors and the agency of objects influence the collection and re-collection of material cultures across time and space. I trace the movement of 30 000 objects in 1965-66 from the original Wellcome Collection in London to what is now known as the Fowler Museum at UCLA. I pay particular attention to the ‘Wellcome Year’ celebrations that marked the arrival of the ‘great gift’ in California, and explore the networks through which the travelling objects moved. From these starting points, and positing an active interpretation of material forms, the article demonstrates how people-object-place relations and shifting systems of value shape the ongoing history and geography of collections within and between certain places. I also explore how sites can be changed as a result of collections' geographies

Ensuring the continued functionality of essential critical infrastructure industries by estimating the workforce impacts of COVID-19

This economic impact assessment was compiled on April 9, 2020 for the Colorado Food Supply Task Force by Jude Bayham and Alexandra E. Hill. Last updated April 9, 2020.Food Systems, Colorado State University

Workforce changes and the food supply chain - understanding and mitigating the effects of COVID-19 on the agricultural workforce

Food Systems, Colorado State University

The metric tide: report of the independent review of the role of metrics in research assessment and management

This report presents the findings and recommendations of the Independent Review of the Role of Metrics in Research Assessment and Management. The review was chaired by Professor James Wilsdon, supported by an independent and multidisciplinary group of experts in scientometrics, research funding, research policy, publishing, university management and administration. This review has gone beyond earlier studies to take a deeper look at potential uses and limitations of research metrics and indicators. It has explored the use of metrics across different disciplines, and assessed their potential contribution to the development of research excellence and impact. It has analysed their role in processes of research assessment, including the next cycle of the Research Excellence Framework (REF). It has considered the changing ways in which universities are using quantitative indicators in their management systems, and the growing power of league tables and rankings. And it has considered the negative or unintended effects of metrics on various aspects of research culture. The report starts by tracing the history of metrics in research management and assessment, in the UK and internationally. It looks at the applicability of metrics within different research cultures, compares the peer review system with metric-based alternatives, and considers what balance might be struck between the two. It charts the development of research management systems within institutions, and examines the effects of the growing use of quantitative indicators on different aspects of research culture, including performance management, equality, diversity, interdisciplinarity, and the ‘gaming’ of assessment systems. The review looks at how different funders are using quantitative indicators, and considers their potential role in research and innovation policy. Finally, it examines the role that metrics played in REF2014, and outlines scenarios for their contribution to future exercises

“PrEP protects us”: Behavioural, normative, and control beliefs influencing pre-exposure prophylaxis uptake among pregnant and breastfeeding women in Zambia

Background Although pre-exposure prophylaxis (PrEP) is recommended for pregnant and breastfeeding women at elevated HIV risk, uptake has been low in Zambia. Methods In in-depth interviews, we explored beliefs about PrEP among 24 HIV-negative pregnant and breastfeeding Zambian women. Thematic analysis was used to identify behavioural, normative and control beliefs likely to influence PrEP uptake. Results Most women viewed PrEP as a good method of protecting themselves and their babies from HIV infection. Partners were cited as key referents in decision making about PrEP use. Many women felt that PrEP use was not entirely in their control. Most reported that they would not use PrEP if their partners did not approve. Health care providers with negative attitudes, long distance to clinics, and extended waiting times were cited as barriers to PrEP uptake. Conclusion HIV-negative pregnant and breastfeeding women had a positive attitude towards PrEP but barriers to uptake are multifaceted

“PrEP protects us”: Behavioural, normative, and control beliefs influencing pre-exposure prophylaxis uptake among pregnant and breastfeeding women in Zambia

BackgroundAlthough pre-exposure prophylaxis (PrEP) is recommended for pregnant and breastfeeding women at elevated HIV risk, uptake has been low in Zambia.MethodsIn in-depth interviews, we explored beliefs about PrEP among 24 HIV-negative pregnant and breastfeeding Zambian women. Thematic analysis was used to identify behavioural, normative and control beliefs likely to influence PrEP uptake.ResultsMost women viewed PrEP as a good method of protecting themselves and their babies from HIV infection. Partners were cited as key referents in decision making about PrEP use. Many women felt that PrEP use was not entirely in their control. Most reported that they would not use PrEP if their partners did not approve. Health care providers with negative attitudes, long distance to clinics, and extended waiting times were cited as barriers to PrEP uptake.ConclusionHIV-negative pregnant and breastfeeding women had a positive attitude towards PrEP but barriers to uptake are multifaceted

Mechanisms of metastasis

Metastasis is an enormously complex process that remains to be a major problem in the management of cancer. The fact that cancer patients might develop metastasis after years or even decades from diagnosis of the primary tumor makes the metastatic process even more complex. Over the years many hypotheses were developed to try to explain the inefficiency of the metastatic process, but none of these theories completely explains the current biological and clinical observations. In this review we summarize some of the proposed models that were developed in attempt to understand the mechanisms of tumor dissemination and colonization as well as metastatic progression

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice