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Paul C Mullan,1 Christopher M Pruitt,2 Kelly A Levasseur,3 Charles G Macias,4 Raina Paul,5 Holly Depinet,6 Anh Thy H Nguyen,7 Elliot Melendez8 1Department of Pediatrics, Division of Emergency Medicine, Eastern Virginia Medical School, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA; 2Department of Pediatrics, Division of Pediatric Emergency Medicine, Medical University of South Carolina, Charleston, SC, USA; 3Pediatric Emergency Medicine, Beaumont Children’s Hospital, Royal Oak, MI, USA; 4Division of Pediatric Emergency Medicine, University Hospitals Rainbow Babies and Children’s, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 5Department of Emergency Medicine, Advocate Children’s Hospital, Park Ridge, IL, USA; 6Division of Emergency Medicine, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH, USA; 7Johns Hopkins All Children’s Institute for Clinical and Translational Research, St. Petersburg, FL, USA; 8Division of Pediatric Critical Care, Connecticut Children’s Medical Center, University of Connecticut, Hartford, CT, USACorrespondence: Paul C Mullan, Email mullan20@gmail.comPurpose: Pediatric sepsis guidelines recommend rapid intravenous fluid (IVF) bolus administration rates (BAR). Recent sepsis studies suggest that rapid BAR may be associated with increased morbidity. We aimed to describe the association between emergency department (ED) IVF BAR and clinical outcomes in pediatric sepsis.Patients and Methods: Secondary post-hoc analysis of retrospective cohort data from 19 hospitals in the Pediatric Septic Shock Collaborative (PSSC) database. Patients with presumed septic shock were defined by severe sepsis/septic shock diagnostic codes, receipt of septic shock therapies, or floor-to-ICU transfers within 12 hours from ED admission for septic shock. Patients (2 months– 21 years) with complete data on weight, antibiotic receipt, bolus timing, and bolus volumes were included. The primary outcome was 30-day mortality. Associations between BAR and mortality and secondary (intubation or non-invasive positive pressure ventilation = NIPPV) outcomes were assessed using unadjusted and adjusted logistic regression.Results: The PSSC database included 6731 patients; 3969 met inclusion and received a median ED volume of 40.2 mL/kg. Seventy-six (1.9%) patients died, 151 (3.8%) were intubated, and 235 (5.9%) had NIPPV administered. The median BAR was 25.7 mL/kg/hr. For each 20 mL/kg/hr increase in BAR, the adjusted odds ratio (aOR) for 30-day mortality [aOR = 1.11 (95% CI 1.01, 1.23)], intubation [aOR = 1.25 (95% CI 1.09, 1.44)], and NIPPV [aOR = 1.20 (95% CI 1.05, 1.38)] significantly increased.Conclusion: Faster ED IVF bolus administration rates in this pediatric sepsis database were associated with higher adjusted odds of death, intubation and NIPPV. Controlled trials are needed to determine if these associations are replicable.Keywords: emergency department, mortality, intubation, collaborative

Introduction: We aimed to assess antibiotic stewardship by quantifying the use of first-dose intravenous (IV) vs oral-only antibiotics and the frequency with which antibiotic class was changed for discharged patients. Secondary aims included the following: evaluation of the relative length of stay (LOS); differences in prescribing patterns between clinician types; differences between academic and community settings; assessment of prescribing patterns among emergency department (ED) diagnoses; and frequency of return visits for patients in each group.Methods: This was a retrospective cohort study including patients presenting to EDs with infections who were discharged from our Midwest healthcare system consisting of 17 community hospitals and one academic center. We included infection type, antibiotic class and route of administration, type of infection, LOS, return visit within two weeks, clinician type, and demographics. Data were collected between June 1, 2018–December 31, 2021 and analyzed using descriptive statistics.Results: We had 77,204 ED visits for patients with infections during the study period, of whom 3,812 received IV antibiotics during their visit. There were more women (62.4%) than men included. Of the 3,812 patients who received IV antibiotics, 1,026 (34.3%) were discharged on a different class of antibiotics than they received. The most common changes were from IV cephalosporin to oral quinolone or penicillin. Patients treated with IV antibiotics prior to discharge had a longer LOS in the ED (median difference of 102 minutes longer for those who received IV antibiotics). There was not a significant difference in the use of IV antibiotics between the academic center and community sites included in the study.Conclusion: Administering IV antibiotics as a first dose prior to oral prescriptions upon discharge is common, as is shifting classes from the IV dose to the oral prescription. This offers an opportunity for intervention to improve antibiotic stewardship for ED patients as well as reduce cost and length of stay.

BACKGROUND: Chronic kidney disease is common, affecting up to 13 % of the global population, and is predicted to become the fifth leading cause of life years lost by 2040. Individuals with end-stage kidney disease commonly develop complications such as protein-energy wasting and cachexia which further worsens their prognosis. The syndrome of renal cachexia is poorly understood, under-diagnosed and even if recognised has limited treatment options. OBJECTIVE: To explore the lived experience of renal cachexia for individuals with end-stage kidney disease and the interrelated experiences of their carers. DESIGN: This interpretive phenomenological study was designed to facilitate an in-depth exploration of how patients and carers experience of renal cachexia. To improve and document the quality, transparency, and consistency of patient and public involvement in this study the Guidance for Reporting Involvement of Patients and the Public-Short Format was followed. SETTING: The study was conducted across two nephrology directorates, within two healthcare trusts in the United Kingdom. PARTICIPANTS: Seven participants who met the inclusion criteria were recruited for this study, four patients (three female, one male) and three carers (two male, one female). METHODS: We employed a purposive sampling strategy. Data collection was conducted between July 2022 and December 2023. Interviews were semi-structured, audio-recorded, transcribed verbatim and analysed in six steps by two researchers using interpretive phenomenological analysis. Ethical approval was approved by the Office for Research Ethics Committees Northern Ireland (Reference: 22/NI/0107). RESULTS: Analysis generated six group experiential themes: the lived experience of appetite loss, functional decline and temporal coping, weight loss a visual metaphor of concern, social withdrawal and vulnerability, the emotional toll of eating challenges and psychological strain amidst a lack of information about cachexia. CONCLUSION: This is the first qualitative study exploring the lived experience of renal cachexia for patients and carers. Our study highlights that psycho-social and educational support is urgently needed. Additionally, healthcare professionals need better information provision to help them to recognise and respond to the needs of this population. Further research is required to develop models of holistic support which could help patients and carers cope with the impact of renal cachexia and optimally manage this syndrome within the family unit. REGISTRATION: N/A.

Abstract Introduction In emergency medicine, triage encompasses more than the initial prioritization of treatment; it also includes decisions about the most suitable level of care and disposition for each patient. However, the increasing use of mobile technology by patients in the emergency department (ED) introduces a new factor. This study aims to explore the relationship between patients’ cellphone use at the time of initial assessment and final disposition in the ED. Methods A prospective, cross-sectional study was conducted on 292 patients who presented to the ED between 9/1/2021 and 8/9/2022. Patients were stratified into two cohorts based on their behavior during the initial assessment: actively using a cell phone (n = 32) or not using a cell phone (n = 259). Final disposition was dichotomously recorded as admission or discharge. Hospital admission, hospital observation, and admission to the ED observation unit were consolidated into the combined category of admission. Results Patients not actively using their cell phone on initial assessment exhibited a discharge rate of 64%, while those engaged with their cellphones displayed notably higher dismissal rates at 94%. The calculated odds ratio (OR) of 8.4 (95% confidence interval: 1.96-36.0, p = 0.004) underscores a significantly heightened likelihood of dismissal among individuals actively using their cellphones, suggesting a potential association between cellphone use and a reduced probability of hospital admission. Conclusion The study suggests an association between cellphone use during initial ED assessment and higher discharge rates. While this introduces a novel concept, the study’s potential contribution to more informed and efficient triage decisions warrants careful consideration in future research and clinical applications.

Abstract Volcanic heating is predicted by theory to affect the velocity of nearby glaciers. However, conclusive studies on a large scale are lacking. Here, we conduct a global comparison of the velocities of glaciers near active volcanoes (i.e. within 5 km) and those located elsewhere ( > 5 km from an active volcano). Our findings show that, when considered over an annual scale (e.g. 2017-2018) and controlling for other factors, glaciers near volcanoes flow 46% faster than those located elsewhere (based on median values). This finding strongly suggests that volcanic heating impacts glacier velocity at a global scale, and supports the idea that glacier velocity monitoring could be a valuable indirect tool to help volcano monitoring and eruption prediction, particularly where volcanic heating (and therefore subglacial melt) intensifies months or years prior to eruptions.

Abstract Background The worldwide number of adults aged 60 years and older is expected to double from 1 billion in 2019 to 2.1 billion by 2050. As the population lives longer, the rising incidence of chronic diseases, cognitive disorders, and behavioral health issues threaten older adults’ health span. Exercising, getting sufficient sleep, and staying mentally and socially active can improve quality of life, increase independence, and potentially lower the risk for Alzheimer’s disease or other dementias. Nonpharmacological approaches might help promote such behaviors. Indoor lighting may impact sleep quality, physical activity, and cognitive function. Dynamically changing indoor lighting brightness and color throughout the day has positive effects on sleep, cognitive function, and physical activity of its occupants. The aim of this study is to investigate how different indoor lighting conditions affect such health measures to promote healthier aging. Methods This protocol is a randomized, cross-over, single-site trial followed by an exploratory third intervention. Up to 70 older adults in independent living residences at a senior living facility will be recruited. During this 16-week study, participants will experience three lighting conditions. Two cohorts will first experience a static and a dynamic lighting condition in a cluster-randomized cross-over design. The static condition lighting will have fixed brightness and color to match lighting typically provided in the facility. For the dynamic condition, brightness and color will change throughout the day with increased brightness in the morning. After the cross-over, both cohorts will experience another dynamic lighting condition with increased morning brightness to determine if there is a saturation effect between light exposure and health-related measures. Light intake, sleep quality, and physical activity will be measured using wearable devices. Sleep, cognitive function, mood, and social engagement will be assessed using surveys and cognitive assessments. Discussion We hypothesize participants will have better sleep quality and greater physical activity during the dynamic lighting compared to the static lighting condition. Additionally, we hypothesize there is a maximal threshold at which health-outcomes improve based on light exposure. Study findings may identify optimal indoor lighting solutions to promote healthy aging for older adults. Trial registration ClinicalTrials.gov Identifier: NCT05978934.

Abstract Background People living with advanced, non-malignant chronic conditions often have extensive and complex care needs. Informal or family caregivers often provide the care and support needed by those with advanced chronic conditions at home. These informal caregivers experience many challenges associated with their caring role, which can impact their own wellbeing. Whilst there is growing evidence around the impact on carers, guidance on support for informal caregivers of patients with advanced, non-malignant, chronic conditions is lacking, with little evidence available on effective psychosocial carer interventions. This systematic review explored existing interventions for caregivers of those with advanced, non-malignant, chronic illness, in order to assess the effectiveness of these interventions in improving psychosocial outcomes. Methods Electronic databases, Medline, CINAHL, EMBASE, and PsycINFO, were searched up to the end of March 2023. Studies meeting the inclusion criteria, focusing on interventions to improve psychosocial outcomes, such as depression, anxiety, quality of life, and caregiver burden, in this cohort of caregivers were included. Data were extracted regarding study setting, design, methods, intervention components, and outcomes. Risk of bias and quality assessment were conducted. Results A total of 5281 articles were screened, ultimately identifying 12 studies for inclusion, reported in 13 publications. A narrative synthesis revealed mixed results. Psychosocial interventions resulted in more significant improvements in psychosocial outcomes than psychoeducational or support interventions, with interventions for carer-patient dyads also reflecting more positive outcomes for caregivers. Evidence-based interventions, guided by an appropriate theoretical model, were reportedly more effective in improving caregiver outcomes. Differences in outcomes were related to intervention development, design, delivery, and outcome assessment. Conclusions This review, to our knowledge, is the first to explore the effectiveness of interventions in improving psychosocial outcomes for caregivers of those with advanced, non-malignant, chronic conditions. The review highlights the need for more robust, sufficiently powered, high-quality trials of evidence-based interventions for caregivers of people with advanced chronic illness. Optimal intervention duration and frequency of sessions are unclear and need further exploration.

Summary In our study, we focused on a particular subtype of aggressive breast cancer called Triple-Negative Breast Cancer (TNBC). We investigated a complex series of events that contribute to poor outcomes in this disease and uncovered a crucial signaling cascade driving tumor growth and progression. At the core of this signaling cascade are three key proteins: SRC, AKT, and ERK2. Together, they form a pathway that activates a transcription factor called Slug. Transcription factors act like molecular switches, controlling the expression of genes. Once Slug is activated, it strongly suppresses genes that would normally restrict cell growth and cell spread. One of the genes downregulated by Slug is TGFB2-AS1. This product of the TGFB2-AS1 gene normally controls levels of its target protein called TGF-beta2 (TGFB2), a protein which has roles in cell growth, cell migration and differentiation. Slug downregulation of TGFB2-AS1 results in higher TGFB2 levels, and this in turn contributes to the uncontrolled growth and spread of cancer cells. TGFB2, and other proteins in this pathway (SRC, AKT, ERK2, and a Slug interactor called LSD1) all maintain the stability of Slug, meaning that Slug levels remain high and drive the aggressive features of this subtype of breast cancer. Overall, our research sheds light on the intricate molecular mechanisms driving aggressive TNBC. It also identifies potential targets for future therapies, aimed at disrupting this harmful signaling pathway and potentially improving patient outcomes for this disease.

Abstract Background General practitioners (GP) and community pharmacists need information about hospital discharge patients’ medicines to continue their management in the community. This necessitates effective communication, collaboration, and reliable information-sharing. However, such handover is inconsistent, and whilst digital systems are in place to transfer information at transitions of care, these systems are passive and clinicians are not prompted about patients’ transitions. There are also gaps in communication between community pharmacists and GPs. These issues impact patient safety, leading to hospital readmissions and increased healthcare costs. Methods A three-phased, multi-method study design is planned to trial a multifaceted intervention to reduce 30-day hospital readmissions. Phase 1 is the co-design of the intervention with stakeholders and end-users; phase 2 is the development of the intervention; phase 3 is a stepped wedge cluster randomised controlled trial with 20 clusters (community pharmacies). Expected intervention components will be a hospital pharmacist navigator, primary care medication management review services, and a digital solution for information sharing. Phase 3 will recruit 10 patients per pharmacy cluster/month to achieve a sample size of 2200 patients powered to detect a 5% absolute reduction in unplanned readmissions from 10% in the control group to 5% in the intervention at 30 days. The randomisation and intervention will occur at the level of the patient’s nominated community pharmacy. Primary analysis will be a comparison of 30-day medication-related hospital readmissions between intervention and control clusters using a mixed effects Poisson regression model with a random effect for cluster (pharmacy) and a fixed effect for each step to account for secular trends. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12624000480583p , registered 19 April 2024.

Einsteins general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Diracs theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive antigravity is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

Abstract Chronic neuroinflammation and microglial activation are key mediators of the secondary injury cascades and cognitive impairment that follow exposure to repetitive mild traumatic brain injury (r-mTBI). Peroxisome proliferator-activated receptor-γ (PPARγ) is expressed on microglia and brain resident myeloid cell types and their signaling plays a major anti-inflammatory role in modulating microglial responses. At chronic timepoints following injury, constitutive PPARγ signaling is thought to be dysregulated, thus releasing the inhibitory brakes on chronically activated microglia. Increasing evidence suggests that thiazolidinediones (TZDs), a class of compounds approved from the treatment of diabetes mellitus, effectively reduce neuroinflammation and chronic microglial activation by activating the peroxisome proliferator-activated receptor-γ (PPARγ). The present study used a closed-head r-mTBI model to investigate the influence of the TZD Pioglitazone on cognitive function and neuroinflammation in the aftermath of r-mTBI exposure. We revealed that Pioglitazone treatment attenuated spatial learning and memory impairments at 6 months post-injury and reduced the expression of reactive microglia and astrocyte markers in the cortex, hippocampus, and corpus callosum. We then examined whether Pioglitazone treatment altered inflammatory signaling mechanisms in isolated microglia and confirmed downregulation of proinflammatory transcription factors and cytokine levels. To further investigate microglial-specific mechanisms underlying PPARγ-mediated neuroprotection, we generated a novel tamoxifen-inducible microglial-specific PPARγ overexpression mouse line and examined its influence on microglial phenotype following injury. Using RNA sequencing, we revealed that PPARγ overexpression ameliorates microglial activation, promotes the activation of pathways associated with wound healing and tissue repair (such as: IL10, IL4 and NGF pathways), and inhibits the adoption of a disease-associated microglia-like (DAM-like) phenotype. This study provides insight into the role of PPARγ as a critical regulator of the neuroinflammatory cascade that follows r-mTBI in mice and demonstrates that the use of PPARγ agonists such as Pioglitazone and newer generation TZDs hold strong therapeutic potential to prevent the chronic neurodegenerative sequelae of r-mTBI.

Pursuing the best European standards and practices of public administration and good governance of territorial and cross-border cooperation to strengthen the potential and institutional capacity of communities and regions of Ukraine is among the priority tasks of Ukraine’s regional policy and European integration course. Therefore, the purpose of the present article is to determine directions for improving the public management mechanism of regional development of territorial communities and regions of Ukraine by applying good governance standards and tools of the Centre of Expertise for Good Governance of the Council of Europe based on the expertise of the Association of European Border Regions. The following scientific methods have been applied in the course of the research: historical, logical and generalization, enabling us to investigate the state and expertise of developing scientific and theoretical provisions, as well as actions taken by subjects and participants of regional policy when developing good governance of territorial and cross-border cooperation. It has been discovered that one of the ways to improve the public management mechanism of the regional development of communities and regions is the introduction of the cyclical mechanism of good governance of the Council of Europe, which consists of: development of standards; creation of tools, recommendations, reports, manuals; research of best practices (golden triangle of good governance “standards – tools – practice”). The necessity of further formulation of directions for improving the public management mechanism of regional development of communities and regions of Ukraine through interaction and partnership with the Association of European Border Regions has been substantiated. Conducting a scientific and theoretical study of the standard and toolkit of good governance “Territorial and cross-border cooperation” of the Council of Europe, as well as the study of the Association of European Border Regions practices have made it possible to focus on the implementation of the standard and toolkit of good governance “Territorial and cross-border cooperation” at the local and regional levels. The results of the research can have practical value for representatives of public authorities and the public sector to update local and regional development strategies based on the implementation of good governance standards and tools

Abstract Background Emergency medicine (EM) trainee comfort level with lumbar puncture (LP) has decreased over time due to changing practice guidelines, particularly amongst pediatric patients. We implemented a “just in time” (JIT) brief educational video based on a previously published LP Performance Scoring Checklist to improve trainee efficiency and competence in LP performance. Methods Our pilot quasi-experimental study took place January-June 2022 within a large, academic Midwestern emergency department (ED) with an established 3-year EM residency program. All 9 interns performed a timed diagnostic LP on an infant LP model in January, scored according to the LP Performance Scoring Checklist. In June, interns repeated the timed LP procedure directly after watching a brief educational video based on major checklist steps. The study was deemed exempt by the Institutional Review Board. Results All interns completed both assessments. At baseline, interns had logged performance of median 2 (IQR 0–5) LPs and spent 12.9 (10.3–14.4) minutes performing the procedure. Post-intervention, interns had logged an additional median 2 (0–5) LPs and completed the procedure faster with an average time of 10.3 (9.7–11.3) minutes (p = 0.004). A median of 5 (4–7) major steps were missed at baseline, compared to 1 (1–2) at time of post-intervention assessment (p = 0.015). Conclusion Development of a brief educational video improved efficiency and competency amongst our intern class in performing an infant LP when viewed Just-In-Time. Similar efforts may improve education and performance of other rare (or decreasing in frequency) procedures within EM training.

Rationale & Objective: Peritoneal dialysis (PD) is a dialysis modality limited by the potential need of transferring to hemodialysis. Optimal hemodialysis vascular access is an arteriovenous fistula. Back-up arteriovenous fistula (bAVF) is a strategy to prevent central venous catheter (CVC) insertion, but its use in the PD population has not been systematically reviewed. Study Design: Systematic review and meta-analysis. Setting & Study Populations: Studies including PD patients with a bAVF and the associated outcomes, including risk of hemodialysis transfer with a CVC and the proportion of bAVFs used. Selection Criteria for Studies: Retrospective or prospective, observational studies, non-randomized or randomized controlled trials. Data Extractions: Vascular access at time of hemodialysis transfer (bAVF vs CVC) for patients with and without a bAVF. The data on bAVF outcomes included bAVFs that stopped working, were never used, and the number of patients requiring hemodialysis. Analytical Approach: Random-effects meta-analysis and meta-proportional analysis were conducted, with risk of bias within studies assessed using the Newcastle-Ottawa Scale. Results: We screened 1,855 studies, 11 of which met the inclusion criteria, comprising 598 (62%) patients with a bAVF and 368 (38%) without. The proportion of bAVFs never used was 69% (95% confidence intervals [CI], 0.58-0.80; I2 = 86.2%). Meta-analysis of 8 studies found no difference in hemodialysis transfer between patients with a bAVF and those without (hazard ratio, 1.14; 95% CI, 0.86-1.51). However, the risk of hemodialysis transfer with a CVC was significantly lower in patients with a bAVF (hazard ratio, 0.43; 95% CI, 0.17-0.68). Limitations: Substantial heterogeneity between the studies and large number of studies with poor quality. Conclusions: bAVF was associated with a high rate of non-utilization but a lower risk of starting hemodialysis via a CVC. Future studies assessing long-term clinical outcomes may provide further insights into the role of bAVF creation in shaping dialysis unit policies. Plain-Language Summary: Peritoneal dialysis (PD) is limited by hemodialysis transfer. The optimal vascular access in hemodialysis is the arteriovenous fistula, yet requirements for maturation often necessitate a central venous catheter (CVC) insertion in acute transfers from PD. A back-up arteriovenous fistula (bAVF) is a strategy used to avoid CVC use in such situations. However, no consensus is currently available on the best approach for bAVF in PD. By conducting a systematic review, we found that 69% of bAVFs were never used. Nevertheless, bAVFs reduced the risk of hemodialysis transfer with a CVC by almost 60%. The studies in the review were small in number and exhibited high heterogeneity, emphasizing that further research is needed to clarify the role and benefits of a bAVF in PD patients.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

BackgroundSedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing. ObjectiveThe DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation. MethodsParticipants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale–Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale–Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care. ResultsThe DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026. ConclusionsThe evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones. Trial RegistrationAustralia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889 International Registered Report Identifier (IRRID)DERR1-10.2196/55129

The ALPHA Collaboration, based at the CERN Antiproton Decelerator, has recently implemented a novel beamline for low energy (≲100 eV) positron and antiproton transport between cylindrical Penning traps that have strong axial magnetic fields. Here, we describe how a combination of semianalytical and numerical calculations was used to optimize the layout and design of this beamline. Using experimental measurements taken during the initial commissioning of the instrument, we evaluate its performance and validate the models used for its development. By combining data from a range of sources, we show that the beamline has a high transfer efficiency and estimate that the percentage of particles captured in the experiments from each bunch is (78±3)% for up to 105 antiprotons and (71±5)% for bunches of up to 107 positrons.