CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications.

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Impact of Medicaid Expansion on Abdominal Surgery Morbidity, Mortality, and Hospital Readmission.

INTRODUCTION: Medicaid expansion's (ME) impact on postoperative outcomes after abdominal surgery remains poorly defined. We aimed to evaluate ME's effect on surgical morbidity, mortality, and readmissions in a state that expanded Medicaid (Virginia) compared to a state that did not (Tennessee) over the same time period. METHODS: Virginia Surgical Quality Collaborative (VSQC) American College of Surgeons National Surgical Quality Improvement Program data for Medicaid, uninsured, and private insurance patients undergoing abdominal procedures before Virginia's ME (3/22/18-12/31/18) were compared with post-ME (1/1/19-12/31/19), as were corresponding non-ME state Tennessee Surgical Quality Collaborative (TSQC) data for the same 2018 and 2019 time periods. Postexpansion odds ratios for 30-d morbidity, 30-d mortality, and 30-d unplanned readmission were estimated using propensity score-adjusted logistic regression models. RESULTS: In Virginia, 4753 abdominal procedures, 2097 pre-ME were compared to 2656 post-ME. In Tennessee, 5956 procedures, 2484 in 2018 were compared to 3472 in 2019. VSQC's proportion of Medicaid population increased following ME (8.9% versus 18.8%, P < 0.001) while uninsured patients decreased (20.4% versus 6.4%, P < 0.001). Post-ME VSQC had fewer 30-d readmissions (12.2% versus 6.0%, P = 0.013). Post-ME VSQC Medicaid patients had significantly lower probability of morbidity (-8.18, 95% confidence interval: -15.52 ∼ -0.84, P = 0.029) and readmission (-6.92, 95% confidence interval: -12.56 ∼ -1.27, P = 0.016) compared to pre-ME. There were no differences in probability of morbidity or readmission in the TSQC Medicaid population between study periods (both P > 0.05); there were no differences in mortality between study periods in VSQC and TSQC patient populations (both P > 0.05). CONCLUSIONS: ME was associated with decreased 30-d morbidity and unplanned readmissions in the VSQC. Data-driven policies accounting for ME benefits should be considered.

Alanine response to low energy synchrotron x-ray radiation.

Objective. The radiation response of alanine is very well characterized in the MV photon energy range where it can be used to determine the dose delivered with an accuracy better than 1%, making it suitable as a secondary standard detector in cancer radiation therapy. This is not the case in the very low energy keV x-ray range where the alanine response is affected by large uncertainties and is strongly dependent on the x-ray beam energy. This motivated the study undertaken here.Approach. Alanine pellets with a nominal thickness of 0.5 mm and diameter of 5 mm were irradiated with monoenergetic x-rays at the Diamond Light Source synchrotron, to quantify their response in the 8-20 keV range relative to60Co radiation. The absorbed dose to graphite was measured with a small portable graphite calorimeter, and the DOSRZnrc code in the EGSnrc Monte Carlo package was used to calculate conversion factors between the measured dose to graphite and the absorbed dose to water delivered to the alanine pellets. GafChromic EBT3 films were used to measure the beam profile for modelling in the MC simulations.Main results. The relative responses measured in this energy range were found to range from 0.616 to 0.643, with a combined relative expanded uncertainty of 3.4%-3.5% (k= 2), where the majority of the uncertainty originated from the uncertainty in the alanine readout, due to the small size of the pellets used.Significance. The measured values were in good agreement with previously published data in the overlapping region of x-ray energies, while this work extended the dataset to lower energies. By measuring the response to monoenergetic x-rays, the response to a more complex broad-spectrum x-ray source can be inferred if the spectrum is known, meaning that this work supports the establishment of alanine as a secondary standard dosimeter for low-energy x-ray sources.

Leveraging existing education innovations to establish a community of practice to promote medical education scholar development.

PROBLEM: While some academic health centers have organizational structures to support educational scholarship, such as Medical Education Research Units (MERU), many education scholars may lack access to such institutional resources to support their research agenda and professional growth. APPROACH: In 2014, as part of an externally funded education grant, three faculty educators established a unique education data management system Research & Evaluation Data for Educational Improvement (REDEI). Lacking an institutional MERU, they established an educational research community of practice (CoP) using REDEI as the research dataset. The senior faculty member's effort to facilitate the group is funded by the Dean's Office. OUTCOMES: The CoP meets every 2 weeks to generate research ideas, discuss analytic approach and strategy, review analyses designed to address or explore a research question, and plans for manuscript development. Our CoP has grown from 3 to 18 members representing faculty educators, administrators, and staff across many departments in the School of Medicine. As of 2021, the REDEI system contains performance data on 1,246 students across all years of undergraduate medical education. To date, we have published 11 peer-reviewed educational research manuscripts. Five learners have served as coauthors (three medical students and two residents), three of whom were first authors. Eleven additional papers are in process. This community of practice supports productivity, provides mentorship, overcomes barriers, and is flexible enough for people to join when they can or when an area of interest is actively under development. NEXT STEPS: We are working on educational interdisciplinary research grant submission and creating collaborations with other institutions. Our focus remains on honing skills in grantsmanship, identification of impactful research questions, application of rigorous methods and instrumentation to address them, and refining process of budget development, timelines, and other planning strategies.

Trainee Reliance on Public Service Loan Forgiveness.

OBJECTIVE: The Public Service Loan Forgiveness (PSLF) program is an option to trainees to help alleviate federal education debt. The prevalence of PSLF utilization and how this may impact career decisions of trainees is unknown. The purpose of this study was to understand the prevalence, impact, and understanding of PSLF participation on trainees. DESIGN: IRB-approved anonymous survey asking study subjects to report demographics, financial status, and reliance on PSLF. In addition, study subjects were asked to report their participation in PSLF, the possible impact of PSLF participation on career decisions, and to identify the qualifications needed to complete PSLF. SETTING: Online anonymous survey. PARTICIPANTS: The survey was offered to all physician trainees in all specialties at the University of Texas, Southwestern, University of Wisconsin, Madison, and University of Michigan, Ann Arbor. RESULTS: There were 934 respondents, yielding a 37.6% response rate. A total of 416/934 (44.5%) respondents were actively or planning on participating in the PSLF program with 175/934 (18.7%) belonging to a surgical specialty. Those belonging to a surgical specialty were more likely to be PSLF participants compared to medical specialties (53.1% versus 42.6%, p = 0.01). For those participating in PSLF, 82/416 (19.7%) stated this participation impacted career decisions. A total of 275/934 (29.4%) respondents obtained and 437/934 (46.8%) wanted to receive formal training/lectures in regards to the PSLF program. Of those actively or planning on participating in the PSLF program, only 58/416 (13.9%) were able to correctly identify all of the qualifications/criteria to complete the program. CONCLUSIONS: A large proportion of trainees rely on the PSLF program for education loan forgiveness with approximately 20% reporting participation impacted career decisions. Additionally, the majority may not fully understand PSLF criteria. Programs should strongly consider providing a formal education regarding PSLF to their trainees.

Incorporating a Whole-Person Perspective in Consumer-Generated Data: Social Determinants, Resilience, and Hidden Patterns.

Given the complex health and social needs of older adults, the rapid growth of the aging population, and the increasing use of information technology in healthcare, there is a critical need for informatics solutions that advance gerontological nursing care and knowledge discovery. This article illustrates the value of standardized data for healthcare quality improvement throughout the life cycle of data capture and reuse. One such informatics solution is the MyStrengths+MyHealth app, which incorporates a whole-person perspective through the Simplified Omaha System Terms assessment, including the social and behavioral determinants of health, as well as resilience. The data describe whole-person health of older adults from MyStrengths+MyHealth for use in clinical encounters and as raw data for research. There is potential to use such standardized data to improve gerontological nursing care at the bedside and for population health management and research.

Disrupting the Fellowship Match: COVID-19 and the Applicant Arms Race.

Resident and fellow selection carried out via "the Match" has historically relied upon in-person interviews to evaluate and rank candidates. However, the COVID-19 pandemic has required fellowship matches and the upcoming Main Residency Match® to become wholly virtual. The 2020 pediatric surgery match offers a unique case study in the benefits and shortcomings of a virtual process and begins a much-needed conversation regarding opportunities for innovation in candidate selection. For many candidates, the application cycle imposes considerable costs - financial, professional, and personal - which have only escalated over time. We draw on our experience from the most recent match cycle to discuss limitations of the traditional Match® and suggest potential solutions to improve the subspecialty interview process moving forward.

Cost effectiveness of intraoperative laparoscopic ultrasound for suspected choledocholithiasis; outcomes from a specialist benign upper gastrointestinal unit.

INTRODUCTION: Common bile duct stones are present in 10% of patients with symptomatic gallstones. One-third of UK patients undergoing cholecystectomy will have preoperative ductal imaging, commonly with magnetic resonance cholangiopancreatography. Intraoperative laparoscopic ultrasound is a valid alternative but is not widely used. The primary aim of this study was to assess cost effectiveness of laparoscopic ultrasound compared with magnetic resonance cholangiopancreatography. MATERIALS AND METHODS: A prospective database of all patients undergoing laparoscopic cholecystectomy between 2015 and 2018 at a district general hospital was assessed. Inclusion criteria were all patients, emergency and elective, with symptomatic gallstones and suspicion of common bile duct stones (derangement of liver function tests with or without dilated common bile duct on preoperative ultrasound, or history of pancreatitis). Patients with known common bile duct stones (magnetic resonance cholangiopancreatography or failed endoscopic retrograde cholangiogram) were excluded. Ninety-day morbidity data were also collected. RESULTS: A total of 420 (334 elective and 86 emergency) patients were suspected to have common bile duct stones and were included in the study. The cost of a laparoscopic ultrasound was £183 per use. The cost of using the magnetic resonance cholangiopancreatography unit was £365 per use. Ten postoperative magnetic resonance cholangiopancreatographies were performed for inconclusive intraoperative imaging. The estimated cost saving was £74,650. Some 128 patients had common bile duct stones detected intraoperatively and treated. There was a false positive rate of 4.7%, and the false negative rate at 90 days was 0.7%. laparoscopic ultrasound use saved 129 bed days for emergency patients and 240 magnetic resonance cholangiopancreatography hours of magnetic resonance imaging. CONCLUSION: The use of laparoscopic ultrasound during laparoscopic cholecystectomy for the detection of common bile duct stone is safe, accurate and cost effective. Equipment and maintenance costs are quickly offset and hospital bed days can be saved with its use.

A plastic surgery service response to COVID-19 in one of the largest teaching hospitals in Europe.

COVID-19 is presenting a colossal challenge to frontline NHS staff. This paper highlights how plastic surgery teams can use their diverse skills and resources in times of crisis. Through effective strategy and leadership we present how we are adapting as a department to serve our plastic surgery patients, other hospital teams and the Trust.

Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8+ T Cell Function Reveals Multiple Limitations of Class I-Selective Histone Deacetylase Inhibitors during HIV-1 Latency Reversal.

Clinical trials investigating histone deacetylase inhibitors (HDACi) to reverse HIV-1 latency aim to expose reservoirs in antiretroviral (ARV)-treated individuals to clearance by immune effectors, yet have not driven measurable reductions in the frequencies of infected cells. We therefore investigated the effects of the class I-selective HDACi nanatinostat and romidepsin on various blocks to latency reversal and elimination, including viral splicing, antigen presentation, and CD8+ T cell function. In ex vivo CD4+ T cells from ARV-suppressed individuals, both HDACi significantly induced viral transcription, but not splicing nor supernatant HIV-1 RNA. In an HIV-1 latency model using autologous CD8+ T cell clones as biosensors of antigen presentation, neither HDACi-treated CD4+ T cell condition induced clone degranulation. Both HDACi also impaired the function of primary CD8+ T cells in viral inhibition assays, with nanatinostat causing less impairment. These findings suggest that spliced or cell-free HIV-1 RNAs are more indicative of antigen expression than unspliced HIV-RNAs and may help to explain the limited abilities of HDACi to generate CD8+ T cell targets in vivoIMPORTANCE Antiretroviral (ARV) drug regimens suppress HIV-1 replication but are unable to cure infection. This leaves people living with HIV-1 burdened by a lifelong commitment to expensive daily medication. Furthermore, it has become clear that ARV therapy does not fully restore health, leaving individuals at elevated risk for cardiovascular disease, certain types of cancers, and neurocognitive disorders, as well as leaving them exposed to stigma. Efforts are therefore under way to develop therapies capable of curing infection. A key focus of these efforts has been on a class of drugs called histone deacetylase inhibitors (HDACi), which have the potential of exposing hidden reservoirs of HIV-1 to elimination by the immune system. Unfortunately, clinical trial results with HDACi have thus far been disappointing. In the current study, we integrate a number of experimental approaches to build a model that provides insights into the limited activity of HDACi in clinical trials and offers direction for future approaches.

Community level socioeconomic status association with surgical outcomes and resource utilisation in a regional cohort: a prospective registry analysis.

BACKGROUND: Socioeconomic status affects surgical outcomes, however these factors are not included in clinical quality improvement data and risk models. We performed a prospective registry analysis to determine if the Distressed Communities Index (DCI), a composite socioeconomic ranking by zip code, could predict risk-adjusted surgical outcomes and resource utilisation. METHODS: All patients undergoing surgery (n=44,451) in a regional quality improvement database (American College of Surgeons-National Surgical Quality Improvement Program ACS-NSQIP) were paired with DCI, ranging from 0-100 (low to high distress) and accounting for unemployment, education level, poverty rate, median income, business growth and housing vacancies. The top quartile of distress was compared to the remainder of the cohort and a mixed effects modeling evaluated ACS-NSQIP risk-adjusted association between DCI and the primary outcomes of surgical complications and resource utilisation. RESULTS: A total of 9369 (21.1%) patients came from severely distressed communities (DCI >75), who had higher rates of most medical comorbidities as well as transfer status (8.4% vs 4.8%, p<0.0001) resulting in higher ACS-NSQIP predicted risk of any complication (8.0% vs 7.1%, p<0.0001). Patients from severely distressed communities had increased 30-day mortality (1.8% vs 1.4%, p=0.01), postoperative complications (9.8% vs 8.5%, p<0.0001), hospital readmission (7.7 vs 6.8, p<0.0001) and resource utilisation. DCI was independently associated with postoperative complications (OR 1.07, 95% CI 1.04 to 1.10, p<0.0001) as well as resource utilisation after adjusting for ACS-NSQIP predicted risk CONCLUSION: Increasing Distressed Communities Index is associated with increased postoperative complications and resource utilisation even after ACS-NSQIP risk adjustment. These findings demonstrate a disparity in surgical outcomes based on community level socioeconomic factors, highlighting the continued need for public health innovation and policy initiatives.

Socioeconomic "Distressed Communities Index" Improves Surgical Risk-adjustment.

OBJECTIVE: We hypothesize the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, will predict risk-adjusted outcomes after surgery. SUMMARY OF BACKGROUND DATA: Socioeconomic status affects surgical outcomes; however, the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database does not account for these factors. METHODS: All ACS NSQIP patients (17,228) undergoing surgery (2005 to 2015) at a large academic institution were paired with the DCI, which accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Developed by the Economic Innovation Group, DCI scores range from 0 (no distress) to 100 (severe distress). Multivariable regressions were used to evaluate ACS NSQIP predicted risk-adjusted effect of DCI on outcomes and inflation-adjusted hospital cost. RESULTS: A total of 4522 (26.2%) patients came from severely distressed communities (top quartile). These patients had higher rates of medical comorbidities, transfer from outside hospital, emergency status, and higher ACS NSQIP predicted risk scores (all P < 0.05). In addition, these patients had greater resource utilization, increased postoperative complications, and higher short- and long-term mortality (all P < 0.05). Risk-adjustment with multivariate regression demonstrated that DCI independently predicts postoperative complications (odds ratio 1.1, P = 0.01) even after accounting for ACS NSQIP predicted risk score. Furthermore, DCI independently predicted inflation-adjusted cost (+$978/quartile, P < 0.0001) after risk adjustment. CONCLUSIONS: The DCI, an established metric for socioeconomic distress, improves ACS NSQIP risk-adjustment to predict outcomes and hospital cost. These findings highlight the impact of socioeconomic status on surgical outcomes and should be integrated into ACS NSQIP risk models.

The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.

A systems-based assessment of Palestine's current and future infrastructure requirements.

The occupied Palestinian territories of West Bank and Gaza Strip are currently experiencing many challenges in the provision of infrastructure services for their inhabitants. This includes an undersupply of infrastructure services across multiple sectors - an issue exacerbated by population growth, increasing urbanisation, economic growth and climate change. We address this challenge by providing a systems-based assessment of Palestine's infrastructure requirements and identifying broad strategies for how those needs might be met. This assessment involved four key components including: 1) defining and assessing the current system and planned infrastructure investments; 2) assessing potential future demand for infrastructure services; 3) identifying alternative strategies for future infrastructure provision beyond planned investments; and 4) analysing the performance of each strategy against a series of key performance indicators. Results from the assessment highlight the magnitude of the current and future need for urgent infrastructure investment in Palestine. The most immediate need is to alleviate the water crises in Gaza Strip, which will require at least twice as much water infrastructure investment over the coming decade than is currently in the pipeline, even if the goal is only to achieve the most basic World Health Organisation water availability requirements. To move beyond this protracted state of crises will then require a doubling of investments across all sectors to bring Palestine up to the standards of services already enjoyed by its neighbours. Such investments can have even greater impact on delivery of infrastructure services through the strategic use of interdependencies between infrastructure sectors, such as water re-use and energy-from-waste. In the pursuit of global sustainable development, the systems-based approach presented here provides an important first step in the assessment of infrastructure needs and opportunities for any country. It is particularly important for states like Palestine where key resources, such as water and energy, are so acutely constrained.