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Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1β levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1β in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.

IntroductionMedication errors are the single most preventable cause of patient harm. 237 million medication errors are estimated to occur annually within the NHS in England alone. The financial burden to the NHS is impactful, but more costly is the significant morbidity and mortality of patients. Multiple patient safety issues around prescribing were highlighted by the submission of over 100 Datix within a 12-month period. Our project, inspired by other similar projects, aimed to highlight areas within our own department that we could address and implement change.AimsOur aim is that 90% of drug charts to meet prescribing standards and to improve confidence of prescribers by September 2024 and reduce the number of medication error related Datix.MethodOur audit looked at prescribing standards of drug charts in paediatrics. We sampled 50 charts in a retrospective audit (25 before doctor changeover and 25 after) during the period Nov 2023- Jan 2024, against 4 sets of criteria based on national prescribing guidelines and trust guidelines.ResultsOur study showed that in all cases prescribing standards were below expected. There was no significant impact of the changeover although standards did slightly worsen.Abstract 8468 Figure 1[Image Omitted. See PDF.]ImprovementFollowing on from this we have instigated remedial actions to improve the prescribing. These actions include: Providing a training tutorial and prescribing workshop for all junior doctors, face to face and regular virtual sessions. Creating and distributing a prescribing handbook. Working towards collaborating a paediatric drug chart. Initial feedback from the team suggests this has helped to clarify requirements and improve prescribing and created our second PDSA cycle. We aim to re-audit in in next 4-6 months period to see the impact of introduction of prescribing handbook.Learning, Reflection And Future EndeavoursOur project was data driven, incorporating evidence from a departmental audit and a review of submitted Datix. With our literature search we were able to increase not only our own knowledge but share this with our colleagues through raising awareness, providing education and focussing on change in attitudes towards prescribing. Additionally, it helped us to develop new leadership skills. Introducing regular quarterly prescribing session may overcome this and, working towards a paediatric drug chart which is already practised in many NHS Trusts and aiming for zero tolerance for prescribing errors.

IntroductionMedication errors are the single most preventable cause of patient harm. 237 million medication errors are estimated to occur annually within the NHS in England alone. The financial burden to the NHS is impactful, but more costly is the significant morbidity and mortality of patients. Multiple patient safety issues around prescribing were highlighted by the submission of over 100 Datix within a 12-month period. Our project, inspired by other similar projects, aimed to highlight areas within our own department that we could address and implement change.AimsOur aim is that 90% of drug charts to meet prescribing standards and to improve confidence of prescribers by September 2024 and reduce the number of medication error related Datix.MethodOur audit looked at prescribing standards of drug charts in paediatrics. We sampled 50 charts in a retrospective audit (25 before doctor changeover and 25 after) during the period Nov 2023- Jan 2024, against 4 sets of criteria based on national prescribing guidelines and trust guidelines.ResultsOur study showed that in all cases prescribing standards were below expected. There was no significant impact of the changeover although standards did slightly worsen.Abstract 8468 Figure 1ImprovementFollowing on from this we have instigated remedial actions to improve the prescribing. These actions include: Providing a training tutorial and prescribing workshop for all junior doctors, face to face and regular virtual sessions. Creating and distributing a prescribing handbook. Working towards collaborating a paediatric drug chart. Initial feedback from the team suggests this has helped to clarify requirements and improve prescribing and created our second PDSA cycle. We aim to re-audit in in next 4-6 months period to see the impact of introduction of prescribing handbook.Learning, Reflection And Future EndeavoursOur project was data driven, incorporating evidence from a departmental audit and a review of submitted Datix. With our literature search we were able to increase not only our own knowledge but share this with our colleagues through raising awareness, providing education and focussing on change in attitudes towards prescribing. Additionally, it helped us to develop new leadership skills. Introducing regular quarterly prescribing session may overcome this and, working towards a paediatric drug chart which is already practised in many NHS Trusts and aiming for zero tolerance for prescribing errors.

Corticosteroids are broadly active and potent anti‐inflammatory agents that, despite the introduction of biologics, remain as the mainstay therapy for many chronic inflammatory diseases, including inflammatory bowel diseases, nephrotic syndrome, rheumatoid arthritis, chronic obstructive pulmonary disease and asthma. Significantly, there are cohorts of these patients with poor sensitivity to steroid treatment even with high doses, which can lead to many iatrogenic side effects. The dose‐limiting toxicity of corticosteroids, and the lack of effective therapeutic alternatives, leads to substantial excess morbidity and healthcare expenditure. We have developed novel murine models of respiratory infection‐induced, severe, steroid‐resistant asthma that recapitulate the hallmark features of the human disease. These models can be used to elucidate novel disease mechanisms and identify new therapeutic targets in severe asthma. Hypothesis‐driven studies can elucidate the roles of specific factors and pathways. Alternatively, 'Omics approaches can be used to rapidly generate new targets. Similar approaches can be used in other diseases.

Reversed phase high performance liquid chromatography (HPLC) interfaced to electrospray tandem mass spectrometry (MS/MS) is commonly used for the identification of peptides from proteolytically cleaved proteins embedded in a polyacrylamide gel matrix as well as for metabolomics screening. HPLC separations are time consuming (30-60 min average), costly (columns and mobile phase reagents), and carry the risk of column carry over between samples. The use of a chip-based nano-ESI platform (Advion NanoMate) based on replaceable nano-tips for sample introduction eliminates sample cross-contamination, provides unchanging sample matrix, and enhances spray stability with attendant increases in reproducibility. Recent papers have established direct infusion nano-ESI-MS/MS utilizing the NanoMate for protein identification of gel spots based on full range MS scans with data dependent MS/MS. In a full range scan, discontinuous ion suppression due to sample matrix can impair identification of putative mass features of interest in both the proteomic and metabolomic workflows. In the current study, an extension of an established direct inject nano-ESI-MS/MS method is described that utilizes the mass filtering capability of an ion-trap for ion packet separation into four narrow mass ranges (50 amu overlap) with segment specific dynamic data dependent peak inclusion for MS/MS fragmentation (total acquisition time of 3 minutes). Comparison of this method with a more traditional nanoLC-MS/MS based protocol utilizing solvent/sample stream splitting to achieve nanoflow demonstrated comparable results for protein identification from polyacrylamide gel matrices. The advantages of this method include full automation, lack of cross-contamination, low cost, and high throughput.

The current study examined the impact of sub-chronic lead (Pb)-exposure upon global protein profile in rodent kidney (blood Pb levels ~50 μg/dL; 5 weeks oral Pb-acetate exposure). Utilizing 2D SDS-PAGE for kidney protein separation, greater than 500 protein spots were analyzed by densitometry following background noise removal, spot alignment, and intensity filtering. Approximately 100 protein spots were identified by ESI-MS/MS with mitochondrial, chaperone, antioxidant, and Pb-binding proteins included. Forty-eight protein spots exhibited significant alterations in abundance (18 identified by ESI-MS/MS) including the increased protein abundance of ketohexokinase, enolase, protein disulfide-isomerase, lamda crystallin, lactamase, and glycerol-3-phosphate dehydrogenase. Decreased protein abundances were observed for α-2 microglobulin, glutamate cysteine ligase, prohibitin, homogentisate 1,2-dioxygenase, alpha-ETF, argininosuccinate synthetase and ATP synthase (H+ transporting). These data support the hypothesis that protein profiles in the kidney are altered following sub-chronic physiologically relevant Pb-exposure.

The demobilisation of the British Army after the First World War launched a mass shift from military dress back into civilian clothing. The subject of the First World War and the demobilisation of the British Army is well-established in scholarly research. The narrative of the soldier's transition from khaki to civvies is, however, less known. This thesis is a study of men's dress during the First World War and its aftermath, focusing on demobilisation and the sartorial shifts shaped by the move from war to peace. It contributes to the historiography of men's dress during the twentieth century by shining a light on the story of the First World War demob suit and the impact of the war on men's dress. To unpack the story of demobilisation, the research explores the meanings and narratives embodied by the army uniform before removing it in exchange for a suit of plain clothes. It examines the ways in which the war shaped men's everyday dress on the home front and had a lasting effect into the post-war years. The research further illustrates how the material culture in the form of wartime dress and its immaterial meanings continued beyond the Armistice. This thesis is shaped by an interdisciplinary approach, combining archival sources with the tactile findings from object-based research of surviving men's dress. Through analysis of archival documents, trade journals and newspapers this thesis traces wartime developments in men's dress. Key to this research are the archival private papers, diaries, memoirs, and oral histories through which this thesis seeks to uncover the personal narratives of lived sartorial experiences. The research reveals the individual stories of uniform personalisation, the distaste amongst civilians for standardised suits and the attempts by demobilised soldiers to ameliorate their demob suits. It engages with post-war social and cultural histories to explore the nuances of everyday dress in the war's aftermath. This thesis shows how dress and personal appearances are interwoven with the lived experience of everyday life and are key in shaping a sense of self.

Objectives. To longitudinally examine the legal landscape of laws requiring abortion patients be informed about the possibility of medication abortion (MAB) “reversal” (in quotes as it does not refer to an evidence-based medical procedure). Methods. We collected legal data on enacted state MAB-reversal laws across all 50 US states and Washington, DC, (collectively, states) from 2012 through 2021. We descriptively analyzed these laws to identify legal variation over time and geography, and conducted a content analysis to identify qualitative themes and patterns in MAB-reversal laws. Results. As of 2021, 14 states (27%)—mostly in the midwestern and southern United States—have enacted MAB-reversal laws. States largely use explicit language to describe reversal, require patients receive information during preabortion counseling, require physicians or physicians' agents to inform patients, instruct patients to contact a health care provider or visit “abortion pill reversal” resources for more information, and require reversal information be posted on state-managed Web sites. Conclusions. Reversal laws continue a dangerous precedent of using unsound science to justify laws regulating abortion access, intrude upon the patient‒provider relationship, and may negatively affect the emotional and physical health of patients seeking an MAB. (Am J Public Health. 2023;113(2):202–212. https://doi.org/10.2105/AJPH.2022.307140 )

This qualitative study explores prostate cancer knowledge and risk in Black college men. Using the Health Belief Model as a guide, focus groups and interviews were conducted with 35 Black males at a historically black college and university. Thematic analysis was conducted and general themes were found. Results indicate that Black college males have very little knowledge and understanding of what their prostate is and what it does. They are also unaware of their risk of developing prostate cancer. Additionally, while many believe prostate cancer is severe, few believe they are susceptible to getting it. These findings suggest more work needs to be done to educate young Black males on not only their prostate and prostate cancer, but on their general health. Efforts should focus on increasing the health knowledge of younger Black males in addition to that of middle-aged and older Black males so that health disparities can decrease.

We investigated low-grade, hemodynamically normal BHI associated with any of three interventions indicating ICU observation. BHI between 01/01/96-6/30/14 were reviewed. Two groups included: Group A (BHI grades 1–3) with normal initial systolic BP and Group B (all other BHI). Interventions necessitating ICU observation were defined with three criteria: PRC transfusion within 24 h, angiography, or laparotomy. Between group and Group A subgroup outcomes were reported. Group A (n = 1088) had lower ISS, LOS, PRCs transfused, and mortality (p < 0.01) than Group B (n = 636). For any of the criteria indicating ICU admission, Group A had a NPV, sensitivity and specificity of 67.9%, 30.3%, and 75.3% respectively; isolated BHI (n = 188) sensitivity, specificity and NPV were 17.8%, 88.1%, and 77.3%. Laparotomy specifically for BHI was 2.0% for Grade I/II, 4.3% for Grade III subgroups. Hemodynamic stability is insufficient as a sole criterion for safe admission of low-grade BHI to a non-ICU environment.