Wellcome Centre for Anti-Infectives Research

Groundwater is a resilient resource that is vital for local water supplies and maintaining baseflow in rivers and streams, particularly during low flow periods. Due to global climate change, the occurrence of meteorological drought is increasing in both frequency and severity, causing or amplifying water scarcity events even in areas considered water rich, like Scotland. While groundwater is generally more resilient to drought than surface water sources, the specific impacts on the resilience of the resource is influenced by local hydrogeology, geography, and climate. To evaluate differences in groundwater response between sites and assess vulnerability and resilience at varying timescales, it is important have standardised parameters to evaluate.The Standardised Groundwater Index (SGI) is a normalisation procedure that can be applied to groundwater level data from observation boreholes to compare drought response more easily between locations. To standardise groundwater data, typical methods use a specific probability distribution which is unlikely to represent variability over large, diverse regions across different seasons or empirical probabilities requiring large sample sizes. Here, in the transformation to standardised units, probability distributions are optimised using Akaike Information Criterion (AIC) to select the most appropriate distribution for each season at each location. Incorporating model fit statistics for each time and site reduces uncertainty in calculations, particularly at the tails of the distribution which is vital for drought studies.Groundwater storage and memory is evaluated across 33 sites in Scotland through the autocorrelation function of the SGI time series and correlated with Standardised Precipitation Evapotranspiration Index (SPEI) to evaluate the time scale of groundwater drought propagation at each location and better characterise storage properties for aquifers of different lithologies and dominant flow types (e.g. intergranular, fractured). Autocorrelation lengths of less than 5 months are common in the fractured flow systems compared to lag periods of 9 months or greater in more highly transmissive aquifers likely dominated by intergranular flow.Hierarchical cluster analysis of the SGI time series provides an added line of evidence to the differential response between hydrogeological units and to identify areas where local changes in geology, structure, or surface water connections could be influencing groundwater response. Characterisation of the groundwater drought response can reveal areas of greater groundwater resilience and provide water managers better metrics to assess the spatiotemporal controls of groundwater drought propagation, along with modelling the timing and magnitude of seasonal groundwater minima.

PTH 6: Health Policy and Health Services 1, B307 (FCSH), September 4, 2025, 16:30 - 17:30Migration is a global issue with significant public health implications. Cross-cultural consultations are considered a vital healthcare adaptation in resettlement countries, yet the provision of trained interpreters, the gold standard, remains difficult to implement. The 2022 Ukraine invasion displaced millions, with 110,000 Ukrainians granted Temporary Protection in Ireland (BoTP). In response, the Irish health service employed multilingual Ukrainian interpreters in specific GP clinics. The effectiveness of this policy is unevaluated, leaving gaps in understanding communication processes in these consultations.The research aim is to empirically examine interpreted consultations between Ukrainian BoTP and GPs in Ireland, analysing interaction dynamics and stakeholders’ perceptions to inform healthcare policy.This is a participatory health research study co-designed with NGO partners. It is a mixed methods, instrumental case study. Purposeful sampling was used to recruit patients (n = 21), interpreters (n = 4) and GPs (n = 3) in primary care clinics established for Ukrainian BoTP. We conducted Discourse Analysis of 21 audio recorded interpreter-facilitated consultations and completed individual interviews with GPs and interpreters about their perceptions of the interpreted consultations.The interpreter’s role is multifaceted, encompassing various responsibilities both within the cross-cultural consultation and the broader clinic setting. GPs and interpreters are broadly satisfied working together and emphasise the value of professional training to optimise communication.The shared cultural, linguistic, and experiential backgrounds of interpreters and patients creates a unique context within these primary care clinics, fostering deeper understanding and facilitating meaning-making between GPs, interpreters and patients. Collaboration between GPs and interpreters can improve patient-centred communication and support patient confidence.This study is the first to evaluate communication processes in interpreted primary care consultations in Ireland, providing key insights into the effectiveness of this policy response. In addressing a critical knowledge gap, it contributes to the broader field of migrant health, informing policies on interpreter access and equitable healthcare delivery.

ABSTRACTBackgroundMaternal health is a fundamental human right, ensuring that all women have access to non‐discriminatory, equitable and high‐quality maternal and reproductive healthcare. Minority groups and migrant populations face significant challenges in accessing maternity services. The Roma are Europe's largest and most marginalised ethnic group. Ireland has a sizable population of Roma migrants, and there is limited information on their experiences of maternal care in Ireland. Their participation in research and user panels is challenging as many lack proficiency in English and tend to have low levels of health literacy. By engaging Roma women in a unique co‐design education and research process, this study aims to identify barriers to accessing care faced by this minority community and understand their experiences of maternity services to enhance equity, accessibility and cultural responsiveness in maternal healthcare.MethodsThis study employed a co‐design approach in partnership with Cairde, a community health organisation, to engage Roma women in exploring their experiences while engaging with maternity services. Eight Roma women participated in four online workshops and completed a questionnaire to share their experiences of pregnancy, childbirth and postnatal care. Workshops incorporated information components, focus groups and Romani translation and interpretation to ensure accessibility. Ethical considerations were maintained, and inductive thematic analysis was conducted using NVivo 20.ResultsThe study involved eight Roma women aged 21–39, many of whom had their first pregnancy between the ages of 14 and 19 and experienced homelessness after the birth of their first child in Ireland. Proficiency in English was limited; five women reported needing a translator while engaging with maternity services. Key patterns identified in Roma women's experiences of maternity care included language barriers, inadequate translation and interpretation support, and systemic discrimination, which leads to delays in antenatal care and heightened emotional distress. Additionally, systemic discrimination manifested through negative interactions with hospital security and administrative staff fostered mistrust and disengagement from healthcare services. However, despite these barriers, many Roma women expressed a preference for Irish maternity care over Romanian services, citing respectful treatment from healthcare professionals, shorter hospital stays, and the provision of essential postnatal supplies.ConclusionsThis study highlights the significant barriers Roma women face in accessing maternity care in Ireland, including language barriers, financial constraints, cultural factors and discrimination. Limited English language proficiency, lack of translators and interpreters, and unfamiliarity with antenatal services often led to delayed or inadequate care, increasing health risks. Despite appreciating respectful treatment from healthcare providers, systemic challenges such as discriminatory practices and low health literacy persist. To address these disparities, it is essential to implement culturally tailored interventions, including the active recruitment and inclusion of Roma women across all levels of the healthcare system. This not only enhances the accessibility and quality of translation and support services but also fosters greater inclusivity, representation and culturally competent care. Future research should focus on expanding representation and designing and evaluating community‐based health initiatives.Patient or Public ContributionThis study collaboration between academic researchers, staff from the Health Service Executive (HSE), and Cairde, a community health development organisation, aimed to involve all stakeholders, including members of the Roma Community, in the co‐design approach that allowed the capture of the experiences and perspectives of Roma women on engaging with maternity services while giving birth in Ireland. Staff from Cairde, including members of the Roma Community, co‐designed a series of workshops and a questionnaire and provided support on the set‐up and delivery of the workshops and questionnaire. This collaboration resulted in the successful delivery of focus groups, informational sessions and a questionnaire, with full participation from the eight participants. Two of the eight Roma women who participated in the workshops were also involved in the co‐design process. Staff from Cairde, including members of the Roma Community, also contributed to the interpretation of findings and drafting of the papers. Partnering with Cairde afforded privileged access to the Roma Community, allowing the research team to engage with this seldom‐heard group. The many barriers to this engagement were addressed through partnering with an organisation with the trust of the Roma community and with the capacity to participate.

This sub-chronic toxicological study explored the potential adverse effects of repaglinide, an antidiabetic medication, on liver and lung function in rats following 30 days of repeated oral exposure. Male Wistar rats were assigned to three groups: a control group, a group receiving repaglinide at the therapeutic dose of 0.7 mg/kg, and a group receiving double the therapeutic dose of 1.4 1.4mg/kg. Blood glucose levels, liver enzymes, and various hematological parameters were measured, and histological examinations of liver and lung tissues were conducted. The study showed that both repaglinide-treated groups had higher levels of liver enzymes (p < 0.05) and changes in hematological parameters, such as higher erythrocytes, hemoglobin, hematocrit, and white blood cells, and lower levels of platelets, compared to the control group. In the lungs of the rats that were treated, histopathological analysis showed that inflammatory cells had moved in, the central vein was swollen, and the walls of the air sacs were getting thicker. These results suggest that repaglinide treatment, especially at higher doses, may lead to adverse effects on liver and lung function in rats, highlighting the need for careful monitoring during its therapeutic use.

The corticosteroid dexamethasone, which is used to treat numerous health conditions, remains the first-line treatment for patients hospitalized with COVID-19 requiring oxygen. Current British National Formulary prescribing advice warns of a "severe theoretical" or "severe anecdotal" risk of drug-drug interactions between dexamethasone and 138 different medications. In humans, dexamethasone is eliminated via the cytochrome P450 monooxygenase system, particularly CYP3A4. It is also described as a human cytochrome P450-inducing agent. To establish factors that affect concomitant therapy and dexamethasone efficacy in the treatment of COVID-19, we used a unique mouse model humanized for cytochrome P450s and the transcription factors that regulate their expression, the pregnane X receptor, and the constitutive androstane receptor. We found that induction of CYP3A4 with the anticancer drug dabrafenib or the herbal medicine St John's wort profoundly reduced dexamethasone exposure. These data suggest that comedications that induce cytochrome P450 expression can have a marked effect on dexamethasone exposure and, potentially, clinical efficacy. We also observed that rather than increasing CYP3A4 expression, dexamethasone at doses equivalent to or higher than those used in the treatment of COVID-19 reduced CYP3A4 expression and increased exposure to dabrafenib. These data indicate the need for a clinical trial to establish the risk of overexposure to comedications during dexamethasone treatment, including the treatment of COVID-19. SIGNIFICANCE STATEMENT: Current prescribing advice identifies a potential theoretical risk of severe side effects when dexamethasone, one of the most widely used drugs in clinical practice, is coadministered with many other drugs; it is, however, difficult to define the magnitude of this risk for specific drug combinations. We describe the use of cytochrome P450-humanized 8HUM mice to predict drug-drug interactions in patients on polypharmacy, a means of generating data that could better inform clinicians regarding foreseeable drug-drug interactions involving dexamethasone.

Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii: A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC50s ≤ 48 µM for A. baumannii QS17-1084 and IC50s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.