Building Geriatric Trauma Programs in Resource-Constrained Environments: Trauma Quality Improvement Program Guideline Implementation at Two Safety Net Hospitals in Southern California.

Background: To improve care of geriatric trauma patients, the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) updated guidelines in 2021. Amid geriatrician shortages in Southern California, 2 Los Angeles County safety net hospitals were tasked with creating a strategy to meet geriatric trauma guidelines despite constrained resources. Methods: All trauma patients ≥ 60 years admitted to a safety net hospital in Southern California were enrolled without exclusions (August 2022-April 2023). Primary outcome was frailty screening with documentation to identify older trauma patients at a high risk for adverse outcomes. Results: Needs assessment discovered no standardized process to identify high-risk geriatric patients, no geriatric care guidelines, and no inpatient geriatric consultation service. An action plan composed of a resident-led frailty screen resulted in identification of high-risk patients. Overall, 217 patients met criteria. Ninety-six patients (44%) successfully underwent frailty screening. Frailty screening compliance increased over the study, beginning at 37% capture in the first month and increasing to 81% in the final study month. After achieving nearly uniform frailty screening, a form was developed for the EMR for ease of documentation, data capture/tracking, and compliance monitoring. Discussion: In this study, creativity, collaboration, and resourcefulness allowed TQIP guideline implementation at 2 county hospitals. A systematic process is now in place to identify and triage high-risk geriatric trauma patients based on frailty screen to receive inpatient medicine consultation for medical comorbidity optimization. Continued interdisciplinary and interfacility collaboration will be crucial for continued delivery of the optimal care to older injured patients.

Understanding the implementation and sustainability needs of evidence-based programs for racial and ethnic minoritized older adults in under-resourced communities with limited aging services.

BACKGROUND: Evidence-based programs (EBPs) for older adults effectively improve health outcomes. However, there is a limited understanding of the unique needs of service providers as they consider adopting, implementing, and maintaining programs for older minority adults in low-income communities with limited aging services. METHODS: We conducted semi-structured interviews with key informants of community-based organizations (CBOs) to understand implementation and sustainability needs of CBOs within four racial and ethnically diverse Los Angeles County geographic areas. We performed thematic analysis of interview transcripts. RESULTS: Interviews were conducted with representatives from 25 senior-serving agencies providing aging-related EBPs. CBO representatives reported implementing EBPs in 8 domains: Falls Prevention (68%), Mental Health (64%), Caregiver Health (48%), Chronic Disease Management (48%), Diabetes Management (36%), Arthritis Management (28%), Physical Activity (24%), and Multiple Conditions Management (8%). Themes are presented using the six domains of the Bass and Judge framework for factors impacting successful and sustained EBP implementation. CBOs in low-income and diverse communities described unique challenges with tailoring interventions based on local community context (literacy, language), cultural context, and locally available resources (technology, safe community spaces, transportation) and faced resource-intensive administrative burdens through staff turnover, data collection, sustainable funding, and networking. CONCLUSIONS: Serving racial and ethnic communities has unique challenges that require tailored approaches and additional resources to ensure equitable access to EBPs for all communities. We describe suggestions for enhancing the effective adoption of EBPs among service agencies in under-resourced and diverse aging communities serving populations with aging-related health disparities.

Informing Dementia Support Programs That Serve Low-Income, Multilingual Communities in a Safety Net Health System: Use of Focus Groups to Identify Specific Needs.

The Centers of Medicare and Medicaid Services recently announced a new voluntary nationwide model. This model aims to provide comprehensive, standard care for people living with dementia and their unpaid caregivers and to enhance health equity in dementia care. However, little is known about the needs of older adults with dementia and their caregivers in a multiethnic and multicultural patient population of a safety net health system. The aim of this study is to include their voices. We conducted four focus groups in English and Spanish to investigate the common needs and barriers unique to the care of patients within the Los Angeles County healthcare system. Using qualitative, iterative analyses of the transcripts, we identified four domains of concern from the dyads (persons with dementia and their caregivers): need for education for dyad-centered care, barriers to resources, dyad safety, and caregiver burden and insight. These domains are interconnected, and the way this patient population experiences these domains may differ compared to those in well-resourced or predominantly English-speaking healthcare settings. Therefore, the identified domains serve as potential building blocks for dementia support programs inclusive of underserved, multicultural populations.

A Systematic Review of Mortality Associations in Patients who Develop Tracheoinnominate Artery Fistula Following Tracheostomy.

OBJECTIVE: Tracheoinnominate artery fistulas (TIFs) are a rare but deadly complication of tracheostomy. Tracheoinnominate artery fistula cases in the literature were summarized in order to understand mortality associations. METHODS: MEDLINE was searched for studies reporting individual characteristics of patients with TIFs after tracheostomy, excluding cases without tracheostomy or with additional procedures at the tracheostomy site. This study followed PRISMA guidelines. RESULTS: 121 TIF patients from 18 case series and 46 case reports were included. The median age was 40 years, and 52.9% were male. The overall mortality rate was 64.5%. There were differences in mortality between cases that presented initially with vs without sentinel bleeding (odds ratio [OR] .34; CI [confidence interval] .16-.73; P = .006). The mortality rate also differed in whether or not the tracheostomy cuff was over-inflated for temporary hemostasis during resuscitation (OR 3.57 (CI 1.57-8.09); P = .002). Treatment compared to no treatment had lower mortality rates (OR .11 (CI 0.04-.32); P < .001); no differences were found if treatment was endovascular vs open surgical. CONCLUSIONS: Mortality is a major concern after detection of a TIF and resuscitation paired with endovascular or open surgical intervention is imperative. Rapidly investigating sentinel bleeds and intervening upon hemorrhage with temporary cuff over inflation may lead to improved outcomes.

Too good for this world: moral bioenhancement and the ethics of making moral misfits.

Persson and Savulescu argue that moral bioenhancement is not only morally permissible; in some cases, it is morally obligatory. In this article, I introduce a new reason to worry about moral enhancement. I adapt the disability concept of misfit to show how moral enhancement could cause extreme moral disempowerment to those enhanced, which would result in moral injury. I argue that any safety framework that guides the development of moral bioenhancement must be sensitive to the problem of moral misfitting. I present the best case for moral bioenhancement before turning to my own worry concerning the development of moral bioenhancement and its practical implications. Finally, I consider a series of objections and responses.

Evaluation of a prototype machine learning tool to semi-automate data extraction for systematic literature reviews.

BACKGROUND: Evidence-based medicine requires synthesis of research through rigorous and time-intensive systematic literature reviews (SLRs), with significant resource expenditure for data extraction from scientific publications. Machine learning may enable the timely completion of SLRs and reduce errors by automating data identification and extraction. METHODS: We evaluated the use of machine learning to extract data from publications related to SLRs in oncology (SLR 1) and Fabry disease (SLR 2). SLR 1 predominantly contained interventional studies and SLR 2 observational studies. Predefined key terms and data were manually annotated to train and test bidirectional encoder representations from transformers (BERT) and bidirectional long-short-term memory machine learning models. Using human annotation as a reference, we assessed the ability of the models to identify biomedical terms of interest (entities) and their relations. We also pretrained BERT on a corpus of 100,000 open access clinical publications and/or enhanced context-dependent entity classification with a conditional random field (CRF) model. Performance was measured using the F1 score, a metric that combines precision and recall. We defined successful matches as partial overlap of entities of the same type. RESULTS: For entity recognition, the pretrained BERT+CRF model had the best performance, with an F1 score of 73% in SLR 1 and 70% in SLR 2. Entity types identified with the highest accuracy were metrics for progression-free survival (SLR 1, F1 score 88%) or for patient age (SLR 2, F1 score 82%). Treatment arm dosage was identified less successfully (F1 scores 60% [SLR 1] and 49% [SLR 2]). The best-performing model for relation extraction, pretrained BERT relation classification, exhibited F1 scores higher than 90% in cases with at least 80 relation examples for a pair of related entity types. CONCLUSIONS: The performance of BERT is enhanced by pretraining with biomedical literature and by combining with a CRF model. With refinement, machine learning may assist with manual data extraction for SLRs.

Scientist Spotlights in Secondary Schools: Student Shifts in Multiple Measures Related to Science Identity after Receiving Written Assignments.

Based on theoretical frameworks of scientist stereotypes, possible selves, and science identity, written assignments were developed to teach science content through biographies and research of counter-stereotypical scientists-Scientist Spotlights (www.scientistspotlights.org). Previous studies on Scientist Spotlight assignments showed significant shifts in how college-level biology students relate to and describe scientists and in their performance in biology courses. However, the outcomes of Scientist Spotlight assignments in secondary schools were yet to be explored. In collaboration with 18 science teachers from 12 schools, this study assessed the impacts of Scientist Spotlight assignments for secondary school students. We used published assessment tools: Relatability prompt; Stereotypes prompt; and Performance/Competence, Interest, and Recognition (PCIR) instrument. Statistical analyses compared students' responses before and after receiving at least three Scientist Spotlight assignments. We observed significant shifts in students' relatability to and descriptions of scientists as well as other science identity measures. Importantly, disaggregating classes by implementation strategies revealed that students' relatability shifts were significant for teachers reporting in-class discussions and not significant for teachers reporting no discussions. Our findings raise questions about contextual and pedagogical influences shaping student outcomes with Scientist Spotlight assignments, like how noncontent Instructor Talk might foster student shifts in aspects of science identity.

EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.

Technology and Universal Health Coverage: Examining the role of digital health.

While there is tremendous promise to leverage technology for UHC, it will require smart, context-specific policies and programming with ample flexibility to adapt as needs and opportunities change - and with robust safeguards to protect privacy, data security, and equity. The health sector, by its very nature of being data intensive, lends itself to the use of technology for analytics to improve health outcomes, respond to public health crises, and efficiently and equitably allocate resources. The first imperative in considering the use of digital health to expand UHC is to remember that digital health is a means to an end, and only one of the available means. Efforts leveraging digital health to move along that path to universality have taken many forms: to increase the number of people reached, to provide enhanced service coverage, and to reduce the financial burdens on individuals in need of health care. Making use of digital health interventions is an evolving process, not a one-time decision point. It is context specific and needs a clear vision to move from pilot interventions to scaled implementation. Technology can be a key tool in achieving UHC but its use has to be strategic, judicious, and cognizant of issues around privacy and patient rights.

Custom-made 3D printed masks for children using non-invasive ventilation: a comparison of 3D scanning technologies and specifications for future clinical service use, guided by patient and professional experience.

Non-invasive ventilation (NIV) is assisted mechanical ventilation delivered via a facemask for people with chronic conditions that affect breathing. Mass-produced masks are available for both the adult and paediatric markets but masks that fit well are difficult to find for children who are small or have asymmetrical facial features. A good fit between the mask and the patient's face to minimise unintentional air leakage is essential to deliver the treatment effectively. We present an innovative use of 3D assessment and manufacturing technologies to deliver novel custom-made facemasks for children for whom a well-fitting standard mask is not available. This paper aims to describe the processes undertaken to investigate and compare currently available technologies for 3D scanning children and to explore the design of a system for creating custom-made paediatric NIV masks within the NHS. The paper therefore considers not only the quality and accuracy of the data, but also other factors such as the time and ease of process. Searches for all currently available scanning technologies were made. Photogrammetry image stitch using a smartphone and a digital camera, and two structured light scanners were selected and compared in the laboratory, in discussion with user groups, and in adult volunteers. Using the processes described, it became apparent that the optimal 3D scanning system for this purpose was the handheld structured light scanner. This option offered both superior accuracy and convenience and was more cost effective.

Comparison of levonorgestrel level and creamatocrit in milk following immediate versus delayed postpartum placement of the levonorgestrel IUD.

BACKGROUND: Breastfeeding and postpartum contraception critically influence infant and maternal health outcomes. In this pilot study, we explore the effects of timing and duration of postpartum levonorgestrel exposure on milk lipid and levonorgestrel content to establish baseline data for future research. METHODS: This sub-study recruited a balanced convenience sample from 259 participants enrolled in a parent randomized controlled trial comparing immediate to delayed (4-8 weeks) postpartum levonorgestrel IUD placement. All planned to breastfeed, self-selected for sub-study participation, and provided the first sample at 4-8 weeks postpartum (before IUD placement for the delayed group) and the second four weeks later. We used the Wilcoxon rank sum (inter-group) and signed rank (intra-group) tests to compare milk lipid content (creamatocrit) and levonorgestrel levels between groups and time points. RESULTS: We recruited 15 participants from the immediate group and 17 from the delayed group with 10 and 12, respectively, providing both early and late samples. Initially, median levonorgestrel concentration of the immediate group (n = 10) (32.5 pg/mL, IQR: 24.8, 59.4) exceeded that of the delayed group (n = 12) (17.5 pg/mL, IQR: 0.0, 25.8) (p = 0.01). Four weeks later, the values aligned: 26.2 pg/mL (IQR: 20.3, 37.3) vs. 28.0 pg/mL (IQR: 25.2, 40.8). Creamatocrits were similar between both groups and timepoints. CONCLUSIONS: Immediate postpartum levonorgestrel IUD placement results in steady, low levels of levonorgestrel in milk without apparent effects on lipid content. These findings provide initial support for the safety of immediate postpartum levonorgestrel IUD initiation, though the study was not powered to detect noninferiority between groups. TRIAL REGISTRATION: This randomized controlled trial was registered with ClinicalTrials.gov (Registry No. NCT01990703) on November 21, 2013.

Staffing in California Public Hospital Palliative Care Clinics: A Report from the California Health Care Foundation Palliative Care in Public Hospitals Learning Community.

Background: Although clinic-based palliative care (PC) services have spread in the United States, little is known about how they function, and no studies have examined clinics that predominantly serve safety net populations. Objectives: To describe the PC clinics operating in safety net institutions in California. Design: Survey completed by PC program leaders Setting/Subjects: PC programs in California, USA, safety net medical centers. Measurements: Descriptive statistics regarding staffing, clinic processes, patients served, and finances. Results: Twelve of 15 programs responded; 10 clinics that met inclusion criteria. All 10 programs use multiple disciplines to deliver care. Average full-time equivalent (FTE) used to staff an average of 2.75 half-day clinics per week includes 0.69 physician FTE, 0.51 nurse practitioner FTE, 1.37 nurse FTE, 0.79 social worker FTE, and 0.52 chaplain FTE. Clinic session schedules include an average of 1.88 new patient appointment slots (standard deviation [SD] = 0.44) and four follow-up appointment slots (SD = 1.95). The nine programs that reported on clinic volumes see 1081 patients annually combined, with an annual average of 120 (SD = 48.53) per program. Encounters per patient averaged 3.04 (SD = 1.59; eight programs reporting). All reported offering seven core PC services: pain/symptom management, comprehensive assessment, care coordination, advance care planning, PC plan of care, emotional support, and social service referrals. An average of 77.4% (SD = 26.81) of clinic financing came from the health systems. Conclusions: Our respondents report using an interdisciplinary team approach to deliver guideline-concordant specialty PC. More research is needed to understand the most effective and efficient staffing models for meeting the PC needs of the safety net population.

Clinical efficacy and safety of first-line treatments in patients with mantle cell lymphoma: A systematic literature review.

Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin's lymphoma (NHL) with a median overall survival (OS) of approximately 3-5 years. Systematic literature reviews (SLRs) identified efficacy and safety data for first-line therapies, reported in randomised controlled trials (RCTs) and non-randomised interventional studies (NRISs). Nine and 20 independent studies were included in the RCT and NRISs SLRs, respectively. Differences in the regimens and patient outcomes varied according to patient age and suitability for autologous stem cell transplantation (ASCT). In elderly patients ineligible for transplant, OS ranged from 40 months to 69.6 months. In young transplant-eligible patients, OS ranged from 53 months to 152.4 months. Despite the paucity of directly comparable evidence on the efficacy and safety of MCL therapies, these SLRs highlight that MCL remains a difficult NHL subtype to treat, with short survival highlighting the unmet need for newer treatments that improve patient outcomes.

Systematic Review of Dementia Support Programs with Multicultural and Multilingual Populations.

BACKGROUND: Dementia care programs have become more common due to a growing number of persons living with dementia and lack of substantial benefit from pharmacologic therapies. Cultural and language differences may present barriers to access and efficacy of these programs. In this article, we aimed to systematically review the current literature regarding outcomes of dementia care programs that included multicultural and non-English speaking populations. METHODS: A systematic review was conducted using four scientific search engines. All studies included in the review are English language, randomized control trials evaluating various care coordination models. The initial search strategy focusing on studies specifically targeting multicultural and non-English speaking populations resulted in too few articles. We expanded our search to articles that included these populations although these populations may not have been the focus of the study. RESULTS: Seven articles met inclusion criteria for final review. Measured outcomes included emergency room use, hospitalizations, provider visits, quality of life indicators, depression scores, and caregiver burden. CONCLUSIONS: Dementia care programs demonstrate significant ability to provide support and improve outcomes for those living with dementia and their caregivers. There is limited research in this field and thus opportunity for further study in underserved and safety net populations including more high-quality randomized controlled trials with larger sample sizes.

Systematic Literature Review of Economic Evaluations, Costs/Resource Use, and Quality of Life in Patients with Mantle Cell Lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. While treatment of patients with MCL and their outcomes are previously published, the availability of heath economics evidence is unclear. OBJECTIVE: The aim of this paper was to conduct a comprehensive review of studies relating to economic evaluations, costs and resource use, and health-related quality of life (HRQoL) in patients with MCL. METHODS: Search strategies were designed to capture studies reporting economic or HRQoL outcomes published in the previous 11 years (2007-2018). The following electronic databases were searched: MEDLINE, Embase, NHS Economic Evaluation Database (NHS EED), and EconLit. In addition, we reviewed congress abstracts presented over the previous 2 years (2015 and 2016; where 2017 proceedings had occurred, these were searched instead of 2015). Publications were screened in duplicate by two reviewers and supplementary searches were carried out on health technology assessment websites. Searches were first conducted in October 2017 and updated in March 2018. FINDINGS: The systematic literature review identified 11 economic evaluations (in 16 publications), seven studies reporting data relating to costs or resource use, and five relating to HRQoL. Four economic evaluations presented results for patients with MCL modelled in the first-line setting, while seven modelled patients in the relapsed/refractory setting. The majority of economic evaluations were conducted using a Markov model with three to five health states. Seven studies assessed resource use and reported adverse events as key drivers of increased costs and resource use. Across the five studies reporting HRQoL, disparate measures were used. Two studies reported improvement in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) total scores following treatment and found that clinical response to treatment was associated with improvement in overall HRQoL. CONCLUSIONS AND RELEVANCE: The published economic and HRQoL evidence in MCL, although scarce, reveals that the economic and HRQoL burden associated with MCL is substantial. In highlighting this evidence, this analysis underlines a critical unmet need for more effective treatments with improved outcomes in MCL.

Site of Azido Substitution in the Sugar Moiety of Azidopyrimidine Nucleosides Influences the Reactivity of Aminyl Radicals Formed by Dissociative Electron Attachment.

In this work, electron-induced site-specific formation of neutral π-type aminyl radicals (RNH·) and their reactions with pyrimidine nucleoside analogs azidolabeled at various positions in the sugar moiety, e.g., at 2'-, 3'-, 4'-, and 5'- sites along with a model compound 3-azido-1-propanol (3AZPrOH), were investigated. Electron paramagnetic resonance (EPR) studies confirmed the site and mechanism of RNH· formation via dissociative electron attachment-mediated loss of N2 and subsequent facile protonation from the solvent employing the 15N-labeled azido group, deuterations at specific sites in the sugar and base, and changing the solvent from H2O to D2O. Reactions of RNH· were investigated employing EPR by warming these samples from 77 K to ca. 170 K. RNH· at a primary carbon site (5'-azido-2',5'-dideoxyuridine, 3AZPrOH) facilely converted to a σ-type iminyl radical (R═N·) via a bimolecular H-atom abstraction forming an α-azidoalkyl radical. RNH· when at a secondary carbon site (e.g., 2'-azido-2'-deoxyuridine) underwent bimolecular electrophilic addition to the C5═C6 double bond of a proximate pyrimidine base. Finally, RNH· at tertiary alkyl carbon (4'-azidocytidine) underwent little reaction. These results show the influence of the stereochemical and electronic environment on RNH· reactivity and allow the selection of those azidonucleosides that would be most effective in augmenting cellular radiation damage.

Teaching Geriatrics and Transitions of Care to Internal Medicine Resident Physicians.

(1) Background: Internal medicine (IM) resident physicians need to be trained to care for older adults and transition them safely across care settings. Objective: The study purpose was to evaluate the efficacy of a curriculum in geriatrics assessment and communication skills for transitions of care (TOCs) to IM resident physicians. (2) Methods: IM residents rotated for 4 weeks on the geriatrics consult service at a large public teaching hospital, where they received didactic lectures and clinical experience in consultation and transitional care. The curriculum was designed to meet consensus guidelines for minimum geriatrics competencies expected of IM residents. Previously validated and published assessment tools were used for geriatrics knowledge and attitudes. Locally developed tools were used to directly observe and rate communication skills, and self-assess geriatrics assessment and health literacy skills. The curriculum was evaluated using a quasi-experimental, nonrandomized, single-group pre- and post-test observational design. Data on 31 subjects were collected over 18 months and analyzed using mixed-effects models. (3) Results: Average knowledge scores improved from 65% to 74% (Δ9%, 95% CI 4-13%, p < 0.001). Communication skills improved by an average of 1.15 points (95% CI 0.66-1.64, p < 0.001) on a 9-point scale. Attitudes did not change significantly. Self-rated confidence in geriatrics assessment and health literacy skills improved modestly. (4) Conclusions: The curriculum is effective in teaching basic geriatrics knowledge and communication skills, and increasing self-confidence in geriatrics assessment skills. In settings where an inpatient geriatrics consult service is feasible, the curriculum may be a model for combining geriatrics and TOC training.

Custom-made 3D printed masks for children using non-invasive ventilation: a feasibility study of production method and testing of outcomes in adult volunteers.

Non-invasive ventilation (NIV) is assisted mechanical ventilation delivered via a facemask for people with chronic conditions that affect breathing. NIV is most commonly delivered via an interface (mask) covering the nose (nasal mask) or the nose and mouth (oronasal mask). The number of children in the UK requiring NIV is currently estimated to be around 5000. Mass-produced masks are available for both the adult and paediatric markets but masks that fit well are difficult to find for children who are small or have asymmetrical facial features. A good conforming fit between the mask and the patient's face to minimise unintentional air leakage is essential to deliver the treatment effectively; most ventilators will trigger an alarm requiring action if such leakage is detected. We present an innovative use of 3D scanning and manufacturing technologies to deliver novel mask-face interfaces to optimise mask fit to the needs of individual patients. Ahead of planned user trials with paediatric patients, the project team trialled the feasibility of the process of creating and printing bespoke masks from 3D scan data and carried out testing of the masks in adult volunteers to select the strongest design concept for the paediatric trial. The evaluation of the process of designing a bespoke mask from scan data, arranging for its manufacture and carrying out user testing has been invaluable in gaining knowledge and discovering the pitfalls and timing bottlenecks in the processes. This allowed the team to iteratively refine the techniques and methods involved, informing user trials later on in the project. It has also provided indicative cost estimates for 3D printed mask prototype components which are useful in project decision making and trial planning. The value of the process extends to considerations for future implementation of the process within a clinical pathway.

The Cytosolic Phospholipase A2α N-terminal C2 Domain Binds and Oligomerizes on Membranes with Positive Curvature.

Group IV phospholipase A2α (cPLA2α) regulates the production of prostaglandins and leukotrienes via the formation of arachidonic acid from membrane phospholipids. The targeting and membrane binding of cPLA2α to the Golgi involves the N-terminal C2 domain, whereas the catalytic domain produces arachidonic acid. Although most studies of cPLA2α concern its catalytic activity, it is also linked to homeostatic processes involving the generation of vesicles that traffic material from the Golgi to the plasma membrane. Here we investigated how membrane curvature influences the homeostatic role of cPLA2α in vesicular trafficking. The cPLA2α C2 domain is known to induce changes in positive membrane curvature, a process which is dependent on cPLA2α membrane penetration. We showed that cPLA2α undergoes C2 domain-dependent oligomerization on membranes in vitro and in cells. We found that the association of the cPLA2α C2 domain with membranes is limited to membranes with positive curvature, and enhanced C2 domain oligomerization was observed on vesicles ~50 nm in diameter. We demonstrated that the cPLA2α C2 domain localizes to cholesterol enriched Golgi-derived vesicles independently of cPLA2α catalytic activity. Moreover, we demonstrate the C2 domain selectively localizes to lipid droplets whereas the full-length enzyme to a much lesser extent. Our results therefore provide novel insight into the molecular forces that mediate C2 domain-dependent membrane localization in vitro and in cells.

An interactive data visualisation application to investigate nosocomial transmission of infections.

Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights. We describe a novel, open-source, application for visualising these data, and demonstrate its utility for investigating nosocomial transmission using a case study of a large outbreak of norovirus infection. Methods: We developed the application using Shiny, a web application framework for R. For the norovirus case study, cases were defined as patients who had a faecal sample collected at the hospital in a winter season that tested positive for norovirus. Patient demographics and ward admission dates were extracted from hospital systems. Detected norovirus strains were genotyped and further characterised through sequencing of the hypervariable P2 domain. The most commonly detected sub-strain was visualised using the interactive application. Results: There were 156 norovirus-positive specimens collected from 107 patients. The most commonly detected sub-strain affected 30 patients in five wards. We used the interactive application to produce three visualisations: a bar chart, a timeline, and a schematic ward plan highlighting plausible transmission links. Visualisations showed credible links between cases on the elderly care ward. Conclusions: Use of the interactive application provided insights into transmission in this large nosocomial outbreak of norovirus, highlighting where infection control practices worked well or could be improved. This is a flexible tool that could be used for investigation of any infection in any hospital by interactively changing parameters. Challenges include integration with hospital systems for extracting data. Prospective use of this application could inform better infection control in real time.