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Digital Preservation of Reproductive Health Resources: Archiving the 8th 14 Nov 2019

On 25th May 2018, Irish citizens voted to remove the controversial "8th Amendment" to the Irish Constitution, opening the way for the introduction of legislation governing the termination of pregnancy in the State. This project intends to provide long term preservation and access to the many at-risk archives generated by grassroots women’s reproductive health movements during the campaign. There is no consensus on the best practice for archiving social media posts, which are supported on third party platforms. It has also been argued that archival curation has been skewed towards the dominant culture. As a result, many of the rich archives of reproductive health generated through the referendum campaign are at-risk. This project aims to · Ingest material from the six collaborating organisations for long term preservation in the DRI · develop best practice for archiving social media · create a registry of at-risk reproductive health archives and support further ingest to the DRI · carry out social science research into best practice, ethics and legalities of archiving this material · Provide training and expertise to reproductive health archives in archival best practice · Collect and preserve additional material on the topic from the public

Amount: £330,630
Funder: The Wellcome Trust
Recipient: Trinity College Dublin

Introducing Assyrian Medicine: healthcare fit for a king 14 Nov 2019

This project makes available for the first time the world’s most standardised, structured and systematised corpus of medical literature prior to Galen: the "Nineveh Medical Encyclopaedia" from the library of Ashurbanipal, King of Assyria (669-c.630 BC). Its broken condition and its use of cuneiform script mean that, almost 200 years after their first discovery, still only glimpses of its content are accessible to medical historians. As such the importance of Assyria’s contribution to the history of medicine remains unrecognised. While fragments of Ashurbanipal’s medical library have long been known, the existence of the Encyclopaedia has only recently been recognised thanks to the reconstruction and translation of an ancient medical catalogue. This discovery allows us now to reconstruct the whole Encyclopaedia from its broken fragments and translate it in full. We will then generate a complete index of drug names and technical vocabulary as found in the compendium, and correlate them against the symptoms they were designed to treat. All this material will be made freely available in enriched digital form. The project will therefore enable researchers to gain a clear understanding of ancient Assyrian medicine and its place in the broader history of medicine.

Amount: £353,277
Funder: The Wellcome Trust
Recipient: British Museum

History Bones: opening up the archive of the Brittle Bone Society 14 Nov 2019

The project will catalogue the archive of the Brittle Bone Society which is primarily held by the University of Dundee Archive Services. Any material remaining at the Society headquarters will be transferred and catalogued and the catalogue will be available online. The material will be re-housed into appropriate archival quality storage containers and a proportion of the material will be digitised. An additional element of the project will be to conduct oral history interviews with Brittle Bone Society members and staff which will become part of the Society's archive. A project board will oversea the progress of the project and will assist in organising a dissemination event. The archive will be fully catalogued allowing researchers to understand its content and identify relevant material The material will be properly preserved ensuring its long term survival The archive will be supplemented by recordings of people associated with the Society which add to the richness of the research resource Awareness of the archive and its research potential will be increased, as will the likelihood of further accruals of material in future Two interdisciplinary dissemination events will allow the discussion of archives relating to disability and the Brittle Bone archive in particular

Amount: £50,783
Funder: The Wellcome Trust
Recipient: University of Dundee

Building a Healthier City 2: slum clearance, council housing and renovation in Bath, 1890-1995 14 Nov 2019

The project will open up valuable new opportunities for research into the relationship between housing and health, answering a clear need for easily accessible archival resources for studies of housing at a local level. It will enable access to significant records relating to slum clearance, provision of council housing, and renovation of unfit properties in Bath between 1890 and 1995. These records are currently uncatalogued and in a poor state of preservation, inaccessible to the research community. We will catalogue approximately 90 linear metres of records to ISAD(G), and publish the resulting catalogue online; the records will be repackaged in accordance with BS4971:2017; remedial conservation will be carried out on those records requiring it. The activities of the project will be strengthened through the input of an Academic Advisory Board which will advise on interaction with the research community and dissemination of the project. As a result of the project, access to a significant collection of records will be assured for researchers now and in the future. It will make a valuable contribution to the evidence base for research into the relationship between local housing policy and health, encouraging a long-term perspective on current housing issues, and informing future policies.

Amount: £169,117
Funder: The Wellcome Trust
Recipient: Bath and North East Somerset Council

Building Becontree 14 Nov 2019

This 18-month project aims to improve the accessibility of collections related to the construction, development, and management of the Becontree Estate through a programme of cataloguing, conservation, digitisation, and outreach utilising the following collections: Building and estate plans London County Council Property Management Files Tuberculosis and Infectious Disease Registers The Dagenham Digest Community publications - tenants’ handbooks, tenants’ gazettes, gardening guides Medical Officer of Health reports Rent books Key outcomes: Creation of fully searchable catalogues to file- and item-level adhering to relevant international standards hosted on the Valence House Collections website and the Archives Hub Conservation, including repair of damaged plans and registers of infectious diseases and the repackaging of other materials using suitable archival-quality packaging Digitisation of key records - building and estate plans, tuberculosis and infectious disease registers, and Dagenham Digests - and long-term preservation of digital surrogates Creation of a project website for dissemination of digitised materials, publication of blogs, and facilitating of comments/memory-sharing from Becontree residents past and present Ingest of public comments from the website into archive catalogues Outreach activities engaging local residents and aiming to build a stronger lasting relationship with an academic audience Writing of research guides to all Becontree-related collections

Amount: £104,661
Funder: The Wellcome Trust
Recipient: London Borough of Barking & Dagenham

Speaking Out: Cataloguing advocacy, support and empowerment in the Lothian Gay and Lesbian Switchboard archives 14 Nov 2019

Speaking Out aims to catalogue, rehouse and selectively digitise archives created by the Lothian Gay and Lesbian Switchboard (LGLS), an activist-run mental and physical health service for LGBT people in the Lothians and beyond. The project will disseminate its findings to academics and the wider public, and address key ethical, visibility and sensitivity issues through collaborative engagement with scholarly and stakeholder communities. Opening on 2 March 1974, LGLS was the UK’s first gay helpline and Scotland's first gay charity. Despite this pioneering history, LGLS archives remain largely invisible to researchers in their current, uncatalogued state. This project aims to open up this collection to researchers through: cataloguing and indexing compliant with archival standards, at levels ensuring maximum general research access; identifying sensitivities/ethical issues and applying appropriate closure periods; using anonymised transcription to provide a way in to selected otherwise-confidential records (encouraging academic researchers to apply for access through established procedures); rehousing records in archival-quality storage; digitising selected material (such as locally-specific newsletters unavailable elsewhere in physical or digital form) to aid no-cost, remote research; promoting the collection to research audiences through targeted activities; recording a small number of oral histories (3 – 5), adding context for researchers.

Amount: £54,548
Funder: The Wellcome Trust
Recipient: University of Edinburgh

The Impact of Pneumococcal and Malaria Vaccines on Bacterial Resistance, Febrile Illness and Antibiotic Usage in Young Children In Malawi 30 Nov 2019

Across much of sub-Saharan Africa, pneumococcal disease (otitis media and pneumonia) and malaria are leading causes febrile illness, and therefore drivers of both appropriate and inappropriate antibiotic use. Prevention through vaccination has the potential to influence antimicrobial resistance (AMR) both directly and indirectly. We are in a unique position to leverage two large funded cluster-randomised vaccine evaluations in Malawi: 13-valent pneumococcal conjugate vaccine (PCV13) schedule change (3+0 to 2+1; extending immunity and potentially herd protection); and RTS,S malaria vaccine introduction. We will ask what are the direct and indirect selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness and antibiotic usage in young children in Malawi? We will determine whether in children S. pneumoniae carriage isolates; the upper respiratory tract resistome; and stool carriage of extended spectrum beta-lactamase (ESBL) E. coli or Klebsiella. We will assess whether the pneumococcal or malaria vaccines alter the frequency of febrile illness and antibiotic use in children

Amount: £764,996
Funder: The Wellcome Trust
Recipient: University College London

Determining the effects of pediatric vaccination status on the burden of antimicrobial-resistant commensal organisms in a Guatemalan community 30 Nov 2019

We are initiating a CDC-funded study of antimicrobial-resistant bacteria in the western highlands of Guatemala. This study is in collaboration with investigators at Washington State University (WSU, USA), University de Valle de Guatemala (UVG), the Guatemalan Ministry of Health and Social Assistance (MSPAS), and the Central America Regional Office of the Centers for Disease Control and Prevention. The goal of this two-stage randomized, cross-sectional study (n=577 households) is (1) to estimate the prevalence of three groups of antimicrobial-resistant bacteria and Group A Streptococcus at the community-level, and (2) to identify risk factors for carriage of the target organisms including antibiotic use and hygiene variables. If funded, the current proposal will add 326 households (with participants Enterobacteriaceae. All vaccinations will be considered, but with the proposed design we hypothesize that we will detect a statistically significant vaccine effect relative to rotavirus and-or pneumococcal vaccinations. Findings from this study will inform the MSPAS vaccination efforts and will be shared with the local, national and international communities (e.g., PAHO and WHO).

Amount: £177,986
Funder: The Wellcome Trust
Recipient: Washington State University

Effect of Rotavirus Vaccine on Antibiotic Prescribing and Antimicrobial Resistance 30 Nov 2019

Rotavirus is the most common cause of severe gastroenteritis in infants and young children. The primary benefit of rotavirus vaccination is prevention of severe diarrheal disease and hospitalizations have been reduced dramatically since vaccine introduction. Rotavirus vaccination may impact antibiotic prescribing and resistance by two mechanisms. First, bacterial agents of gastroenteritis are often treated with antibiotics. Since aetiology is usually not known at the time of the medical encounter, antibiotics are frequently prescribed for viral gastroenteritis even though they are not recommended. Second, antibiotics, whether prescribed for gastroenteritis or infection at other sites, may disrupt the enteric microbiome. This may in turn lead to other secondary bacterial infections, mainly Clostridium difficile infection (CDI). C difficile is inherently resistant to most groups of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and fluoroquinolones, hence treatment options are limited. In this study, we aim to 1) estimate the effect of rotavirus vaccination on antibiotic prescribing 2) estimate the effect of rotavirus vaccination on CDI. We will conduct a large retrospective cohort study constructed from MarketScan databases. Analysis will be performed using longitudinal, individual-level data. These findings can provide evidence for national and international bodies for vaccine decision-making and antimicrobial resistance control strategies.

Amount: £267,005
Funder: The Wellcome Trust
Recipient: Emory University

Reducing antibiotic prescribing through a prioritized vaccination strategy 30 Nov 2019

Prioritizing vaccine development to focus on pathogens that drive the most antibiotic prescribing will have multiple advantages: reducing the burden of disease, reducing the extent of antibiotic use, and thus reducing the selective pressures driving antimicrobial resistance. In this proposal, we will (1) test the hypothesis that recent declines in outpatient antibiotic prescribing in the US are associated with reductions in pneumococcal disease attributable to PCV13 uptake and (2) estimate the antibiotic prescribing attributable to the most common pathogens and variation by age, demographic, and geography. To do so, we will use large representative nationwide datasets from the US, including insurance claims, public health surveillance, and a national immunization survey. The deliverables from this project will include estimates of the impact of PCV13 on outpatient prescribing and quantification of the expected reductions in antibiotic prescribing given vaccines for common pathogens. We expect that the results from these studies will establish (1) robust estimates of the reductions in outpatient antibiotic prescribing achieved by PCV13, as an exemplar of what vaccines can accomplish; and (2) priorities for vaccines to target in terms of impact on antibiotic prescribing and thus on antimicrobial resistance.

Understanding the contribution of influenza vaccines to antibiotic prescribing in the UK population. 30 Nov 2019

Vaccination should reduce antibioticl prescribing (AP), the driver of antimicrobial resistance. Looking for reductions in Randomised Controlled Trials of vaccine is problematic as they are usually powered for large effect sizes of specific end-points. An alternative approach is to undertake observational studies using large routine data sources. The problem with this approach is ensuring major confounding is identified and accounted for when linking vaccine status and outcome and, demonstrating a causal relationship. We will conduct an observational study using the Clinical Practice Research Datalink (2007-2019) and The Health Improvement Network (THIN) (2007-2019) from the United Kingdom. Our primary aim is to measure AM prescribing in adults over 65 and children under 5 by frequency of influenza vaccination. We will use three complimentary approaches and different methods to adjust for confounding: 1 A Self-controlled case series – comparing annual AM prescribing within individuals by annual receipt of influenza vaccine and vaccine/pathogen match. 2 A Cohort study - balancing comparator populations using propensity scoring to control for major determinants of health care utilisation and underlying health status. 3 An Interrupted time series analyses – investigating paediatric influenza vaccine uptake (September 2013) and AM prescribing

Amount: £237,892
Funder: The Wellcome Trust
Recipient: University of Liverpool

Could vaccinating at risk populations with Meningococcal B vaccine reduce incidence and antimicrobial resistance in gonococcal infections in the UK? 30 Nov 2019

Antimicrobial resistance (AMR) threatens public health and individual patient care. Gonococcal (GC) infection incidence has been increasing year on year for the last decade in the UK. AMR in GC infection is relatively low in the UK, but it has been increasing too. We propose to develop, simulate and parameterise a model for Neisseria gonorrhoeae and Neisseria meningitidis circulation. Control of gonorrhoea is likely to become increasingly difficult due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recent studies where meningococcal B (MenB) vaccine is given to adolescents reported a reduction in incidence rates of GC in those vaccinated, as the vaccine potentially offers some cross protection. Counterfactual scenarios can be investigated with a model (with potential uncertainty in outputs) to consider appropriate health economic evaluation. Goals: Develop a transmission model of GC and MenB infection for the UK Investigate the cost-effectiveness of MenB vaccine in infants, adolescents and targeted at-risk populations in reducing MenB and GC infection incidence and AMR. Investigate the potential impact in areas of low, medium and high incidence of GC infection and low and high level AMR in GC.

Amount: £201,273
Funder: The Wellcome Trust
Recipient: University of Manchester

ROTA-biotic: measuring the impact of rotavirus vaccines on pediatric antibiotic usage 30 Nov 2019

Rotavirus is the most common aetiology of serious gastroenteritis in young children. Despite antibiotics not being indicated in its treatment, gastroenteritis remains a very common cause for antibiotic prescribing in low-income settings. We hypothesize that effective rotavirus vaccination can reduce diarrheal episodes and thereby unnecessary antibiotic usage in young children in low-income settings. This study aims to evaluate the impact of rotavirus vaccination on antibiotic usage. Specifically, the study will quantify how differences in rotavirus vaccine efficacy impact days of prescription and non-prescription antibiotic usage in the first 2 years of life among two large cohorts of children in Zambia and Ghana. The key goal is to understand the effect of rotavirus vaccine efficacy on antibiotic usage and household antibiotic costs. This will generate evidence needed to inform policy-makers seeking to introduce new rotavirus vaccines into national vaccination programmes, ofpotential, and often under-appreciated, secondary effects of rotavirus vaccine implementation on antibiotic usage. This proposal will be conducted within a planned phase III randomised controlled trial comparing the efficacy of a new parenteral trivalent P2-VP8 subunit rotavirus vaccine to the oral live attenuated vaccine, Rotarix®, against severe rotavirus gastroenteritis in the first 2 years of life in Zambia and Ghana.

Effectiveness of vaccines to prevent antibiotic prescribing for acute respiratory tract infections in high risk adults 30 Nov 2019

In high income countries the greatest use of antibiotics is in community (primary care) settings in the context of acute respiratory tract infections. Within these settings, both the very young, the very old and those with respiratory conditions such as asthma and chronic obstructive pulmonary disease are known to be the greatest antibiotic users. While there are a number of vaccines routinely provided that protect against acute respiratory tract infections, there is limited empirical data quantifying the potential benefit of vaccines to reduce antibiotic use for respiratory tract infections, particularly in adult populations. In this project we will use a large-scale database of electronic general practice records to quantify, in older adults, the effectiveness of influenza, pertussis and pneumococcal vaccines in reducing primary care presentations for acute respiratory tract infections and subsequent antibiotic prescribing. We will focus on high risk groups defined by age and/or co-morbidity (asthma and chronic obstructive pulmonary disease). We will use these estimates of vaccine effectiveness to model the absolute reductions in antibiotic use that could be obtained by increasing vaccine coverage in different adult sub-groups. This evidence will enable policymakers to better prioritise strategies to increase uptake of these vaccines.

Amount: £179,852
Funder: The Wellcome Trust
Recipient: University of New South Wales

Epidemiological and mechanistic studies on the role of pneumococcal conjugate vaccine in antimicrobial resistance in Laos 30 Nov 2019

PCVs prevent pneumonia and invasive pneumococcal disease (IPD). The serotypes contained within PCV are those which carry most antimicrobial resistance (AMR). PCVs reduce the carriage of PCV serotypes, and also limit the use of antibiotics by preventing pneumococcal infections. In the US, the 13-valent PCV (PCV13) reduced childhood IPD AMR by > 75%. Despite a high pneumonia burden in Asia, very few countries have adopted PCV into their national immunisation programs. PCV may have a substantial role in reducing AMR and it is vital that the role of PCV in reducing AMR in this region is determined. PCV introduction has also led to serotype replacement with serotypes that are not included in the vaccine (NVTs). It is therefore important to define pneumococcal population changes and identify emergent clones in the post-PCV era. In 2013, we commenced pneumococcal carriage surveillance in Laos in children aged 2- 59 months with acute respiratory infection (ARI). Our proposed study in Laos will: a) determine the PCV13 effectiveness against AMR in pneumococcal carriage isolates; b) determine the AMR and virulence of emerging NVTs; and c) investigate using a life-like system the recombination frequency for the acquisition of resistance genes, and secondary chromosomal insertions, in pneumococcal NVTs.

Amount: £404,673
Funder: The Wellcome Trust
Recipient: Murdoch Children's Research Institute

Vaccine-avertable antimicrobial prescribing from influenza and RSV: a mixed-methods observational study 30 Nov 2019

Vaccines against viruses can reduce antibiotic prescribing by reducing the incidence of viral infections that are inappropriately treated with antibiotics, as well as by reducing the incidence of secondary bacterial infections caused by viral infections. We will estimate the magnitude of this effect for influenza vaccination and the potential magnitude for Respiratory Syncitial Virus (RSV) vaccination and enhanced influenza vaccination. First, we willestimate the antimicrobial prescribing attributable to RSV and influenza in the Kaiser Permanente population in Northern California, USA, in total and by drug class and age group. Next, we will estimate the antimicrobial prescribing currently averted by influenza vaccination by comparing antimicrobial prescribing in (1) persons who have not received influenza vaccine vs. (2) persons who have, controlling for age and location within northern California, in aggregate and stratified by age and antimicrobial class. Using these results, we will estimate the number and proportion of antimicrobial prescriptions that may potentially be averted by improved influenza vaccines and (separately) by RSV vaccines that are now investigational, assuming various possible levels of coverage and effectiveness. Notable features of our analysis will be extensive measures to avoid confounding and an examination of waning of influenza prescribing effects with time since vaccination.

Impact of Shigella, rotavirus, and other enteric vaccines on etiology-specific diarrhea, antibiotic use, and exposure of subclinical infections to antibiotics among children in low-resource settings 30 Nov 2019

Diarrhoeal disease, caused by leading aetiologies of Shigella and rotavirus, is a major contributor to antimicrobial resistance (AMR) due to increasing incidence of drug-resistant episodes and frequent treatment with antibiotics. We propose to quantify the comprehensive impact of enteric vaccines in combating AMR by preventing drug-resistant diarrhoea episodes and reducing antibiotic use using data from the MAL-ED study, a longitudinal birth cohort conducted in 8 low-resource sites. Specifically, we will: 1) quantify the incidence of antibiotic use and of antibiotic exposure to subclinical enteric infections that is attributable to the treatment of aetiology-specific diarrhoea episodes, 2) estimate reductions in the incidence of aetiology-specific diarrhoea and antibiotic exposure achievable by vaccines against Shigella, rotavirus, and other enteric pathogens, and 3) estimate the worldwide impact of enteric vaccine introduction on aetiology-specific diarrhoea, antibiotic use, and antibiotic exposure to subclinical infections using data from Demographic Health Surveys and Multiple Indicator Cluster Surveys. These results will generate precise estimates of enteric vaccine impact, most importantly for Shigella vaccines, which have been prioritized for development, and for rotavirus vaccines, which continue to be adopted globally. These quantitative estimates will inform advocacy efforts for continued support and provide relevant data for comprehensive analyses of cost-effectiveness.

Amount: £239,190
Funder: The Wellcome Trust
Recipient: University of Virginia

Impact of a Typhoid Conjugate Vaccine Campaign on Antimicrobial Use in Harare, Zimbabwe 30 Nov 2019

Typhoid fever is a common cause of non-specific febrile illness in low-resource settings. Empirical treatment for typhoid may be a major driver of AMR in typhoid-endemic communities, where estimates suggest that up to 25 additional cases receive antimicrobial treatment for each one confirmed. Harare in Zimbabwe has experienced a major increase in typhoid since 2016, with recent emergence of ciprofloxacin-resistance. In February 2019 a mass typhoid vaccine campaign was performed, targeting infants and children living in 9 affected suburbs with the new typhoid conjugate vaccine (TCV). In work being performed at primary health clinics in these densely-populated suburbs as part of the FIEBRE study, which aims to assess the causes of febrile illness in low-resource settings, we have already identified a significant reduction in typhoid in vaccinated children. In this project our key goals are to investigate the impact of the 2019 mass TCV campaign on antimicrobial resistance in S. Typhi and on antimicrobial prescribing and related practices in community clinics. Defining these effects will have major policy implications for TCV use, both locally, in determining the benefits of further routine/repeat vaccination, and internationally to inform estimates of the direct and indirect impacts on AMR infection and antimicrobial use.

Amount: £193,863
Funder: The Wellcome Trust
Recipient: University of Sheffield

Impact of a Typhoid Conjugate Vaccine Campaign on Antimicrobial Use in Harare, Zimbabwe 30 Nov 2019

Typhoid fever is a common cause of non-specific febrile illness in low-resource settings. Empirical treatment for typhoid may be a major driver of AMR in typhoid-endemic communities, where estimates suggest that up to 25 additional cases receive antimicrobial treatment for each one confirmed. Harare in Zimbabwe has experienced a major increase in typhoid since 2016, with recent emergence of ciprofloxacin-resistance. In February 2019 a mass typhoid vaccine campaign was performed, targeting infants and children living in 9 affected suburbs with the new typhoid conjugate vaccine (TCV). In work being performed at primary health clinics in these densely-populated suburbs as part of the FIEBRE study, which aims to assess the causes of febrile illness in low-resource settings, we have already identified a significant reduction in typhoid in vaccinated children. In this project our key goals are to investigate the impact of the 2019 mass TCV campaign on antimicrobial resistance in S. Typhi and on antimicrobial prescribing and related practices in community clinics. Defining these effects will have major policy implications for TCV use, both locally, in determining the benefits of further routine/repeat vaccination, and internationally to inform estimates of the direct and indirect impacts on AMR infection and antimicrobial use.

FAIR and open multilingual clinical trials data in Wikidata and Wikipedia 16 Oct 2019

Primary deliverables (Linked Open Data for production) integrate clinical trials cataloging data from sites like into Wikidata translate a limited vocabulary from to underserved languages, namely Hindi, Bengali, and Swahili Secondary deliverables (cultural products to promote diversity and good ethics) document Wikidata as a research interface for clinical trials (English, Hindi, Bengali, and Swahili) publish a general-interest essay on ethical considerations of making medical research data newly accessible Wikidata is currently the central hub of the open Semantic Web and a portal to downstream reuse. While various sources such as libraries, repositories, and provide open data, the easiest way to make information broadly accessible to the general public as well as professionals and researchers is integration into a Semantic Web portal like Wikidata which encourages further reuse. This project will integrate into Wikidata, making it accessible to the Open Semantic Web and beginning the process of mapping its metadata with PubMed, disambiguated names of researchers, geolocation of study sites, portfolio of sponsors, and drug databases .Furthermore, we will translate the search interface to those named underserved languages as a precedent in global collaboration. If we are successful to the limits of our expectations, then clinical trials data published to date will be free and open and in the Semantic Web. Furthermore, we will set the precedent in this project that linguistic diversity must be central to open data projects of global interest.

Amount: £43,415
Funder: The Wellcome Trust
Recipient: University of Virginia