Search

Changes in vertical column concentration, size distribution, and surface concentration of aerosol associated with the lockdown imposed by the COVID-19 pandemic in 2020 over the Ahmedabad region in Gujarat State, India, were analyzed. The results are compared with changes over selected Indo-Gangetic Plain (IGP) regions. On 25 March 2020, the prime minister of India declared a complete lockdown throughout the country and later lifted restrictions in a phased manner. Aerosol optical depth (AOD) over the Ahmedabad region on 29 March dropped to as low as 0.11, and in the first two weeks of lockdown, the weekly average AOD was only 0.18. On almost all days of the lockdown period, AOD over the Ahmedabad region was lower than the decadal mean. It was found that the Ahmedabad region responded differently to lockdown conditions compared to the IGP regions. During the first lockdown phase, AOD decreased by about 29% compared to the pre-lockdown period over the Ahmedabad region. However, the average reduction over the IGP was much more, about 50%. The average Angstrom exponent (AE) of 0.96 during the pre-lockdown period over the Ahmedabad region increased phase-wise to 1.36 during the L3 lockdown phase, indicating dominance of fine-mode particles during the lockdown period. It suggests a reduction in anthropogenically produced coarse-mode particles, typically dust produced by vehicular movement, construction, and industrial activities. However, on the other hand, over the IGP region, the high dominance of fine-mode particles during the pre-lockdown period had changed to a high dominance of coarse-mode particles, especially over the Delhi region. This indicates a reduction in anthropogenically produced fine-mode particles, which are mainly generated by fossil and biofuels/biomass combustion, over the IGP region by lockdown conditions. Within a few days of lockdown, PM2.5 was reduced by 64% and 76% over the Ahmedabad and Delhi regions, respectively. The lockdown imposed by the pandemic provided an excellent opportunity to ascertain background aerosol conditions in the atmosphere.

Abstract Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

Abstract Objectives Despite the significant disease burden due to cardiac arrest, there is a relative paucity of randomized controlled trials (RCTs) to inform definitive management. We aimed to evaluate the current scope of cardiac arrest RCTs published between 2015 and 2022. Methods We conducted a search in October 2023 of MEDLINE, Embase, and Web of Science for cardiac arrest RCTs. We included trials published between 2015 and 2022 enrolling human subjects suffering from non‐traumatic cardiac arrest. Descriptive statistics were reported and the Mann Kendall test was used to evaluate for temporal trends in the number of trials published annually. Results We identified 1764 unique publications, 87 RCTs were included after title/abstract and full‐text review. We found no significant increase in trials published annually (eight in 2015 and 16 in 2022, p = 1.0). Geographic analysis of study centers found 31 countries represented; Denmark (n = 13, 15%) and the United States (n = 9, 10%) conducted the majority of trials. Nearly all trials included adults (n = 84, 97%) and few included children (n = 9, 10%). The majority of trials focused on out‐of‐hospital cardiac arrest (n = 62, 71%). Thirty‐eight (44%) trials used an intervention characterized as a process improvement; 28 (32%) interventions were characterized as a drug and 20 (23%) as a device. Interventions were implemented with similar frequency in the prehospital (33%) and intensive care unit (38%) setting, as well as similarly between the intra‐arrest (53%) and post‐arrest (46%) periods. Twenty (27%) trials selected a primary outcome of survival at ≥ 28 days. Conclusions Publication of cardiac arrest RCTs remained constant between 2015 and 2022. We identified significant gaps including a lack of trials examining in‐hospital cardiac arrest and pediatric patients.

Abstract Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, tissue homeostasis, and optimization of biomechanical tissue functions. Perlecan‐mediated osmotic mechanotransduction serves to regulate the metabolic activity of cells in tissues subjected to tension, compression, or shear. Perlecan interacts with a vast array of extracellular matrix (ECM) proteins through which it stabilizes tissues and regulates the proliferation or differentiation of resident cell populations. Here we examine the roles of the HS‐proteoglycan perlecan in the normal and destabilized intervertebral disc. The intervertebral disc cell has evolved to survive in a hostile weight bearing, acidic, low oxygen tension, and low nutrition environment, and perlecan provides cytoprotection, shields disc cells from excessive compressive forces, and sequesters a range of growth factors in the disc cell environment where they aid in cellular survival, proliferation, and differentiation. The cells in mechanically destabilized connective tissues attempt to re‐establish optimal tissue composition and tissue functional properties by changing the properties of their ECM, in the process of chondroid metaplasia. We explore the possibility that perlecan assists in these cell‐mediated tissue remodeling responses by regulating disc cell anabolism. Perlecan's mechano‐osmotic transductive property may be of potential therapeutic application.

OBJECTIVE During the SARS-CoV-2 pandemic, hospital visitation restrictions hindered patients’ access to vital social support. This study explores the impact and feasibility of a student-led program facilitating audiovisual communication between inpatient rehabilitation patients and their caregivers. METHODS The study design employed a prospective observational approach, and convenience sampling enrolled 99 participants, including 33 patients, 33 caregivers, and 33 medical students. From September 2021 to March 2022, eligible patients admitted to an inpatient rehabilitation hospital identified a caregiver and participated in a 30-minute audiovisual call organized by a medical student. Post-visit surveys via RedCap were completed by all participants and covered limitations in video calls, program benefits, comfort levels in video conferencing, and overall program ratings. The study adopted a quantitative research paradigm for data analysis. Statistical analysis utilized pairwise McNemar's and Wilcoxon's test for inter-group comparison. RESULTS Patients, caregivers, and medical students all reported positive outcomes in program offerings including providing social support, decreasing feelings of isolation, and providing a feeling of connection. Patients rated the program 4.82 ± 0.47 on a Likert scale, with 97% recommending it to others, even beyond visitation restrictions. The most common diagnosis among patients was stroke (30%), highlighting the program's potential applicability across diverse patient populations. Caregivers rated the program 4.59 ± 0.87 and expressed a desire for its continuation post-restrictions (80%). Medical students (81%) recommended the program, citing benefits in reducing social isolation and gaining clinical experience. No statistical differences were observed between groups in emotional and humanistic domains. CONCLUSION This study highlights the potential for programs to utilize technology to address social isolation in the healthcare setting. When public health restrictions occur, medical educators should consider opportunities to support and foster innovation for student-led programs. Further research should explore broader impacts on healthcare outcomes and medical education.

Inadequate management of food waste (FW) has contributed to environmental degradation. Bioconversion of FW using black soldier fly larvae has proven to be a safe and cost-effective method for FW management. However, limited studies exist on the influence of starter feeds. The impact of rice bran, wheat bran, and chick mash as starter feeds was evaluated by investigating the optimal larval weight, substrate reduction, feed conversion ratio (FCR), and bioconversion rate (BCR) of the larvae after initial treatment in rice bran (T1), wheat bran (T2), chick mash (T3), and control (T4). The highest mean larval weight observed was 0.22 g in T3 followed by 0.18, 0.16, and 0.13 g in T2, T4, and T1, respectively. A similar trend was observed for substrate reduction and BCR. Nevertheless, the obtained substrate reduction range of 75.5–82.8% was comparable with the published ranges. The best performance in T3 may be attributed to high protein and nitrogen content in chick mash, while the lowest performance is attributed to high ash content in rice bran, which negatively affected the BCR. It can be concluded that the physico-chemical properties of the starter feeds strongly determine the growth and development of larvae. HIGHLIGHTS The physico-chemical properties of starter feeds should be considered for the selection of the best starter feed for the rearing of the BSF.; This study recommends chick mash as the best starter feed.; Food waste is a suitable substrate for growing BSF.; Due to its high ash content, this study does not recommend rice bran as a starter feed in rearing BSF larvae.;

Abstract Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

To evaluate the efficacy of physical therapy (PT) to alleviate symptomatic thoracic radiculopathy (TR) without the use of invasive procedures. Database search was conducted by an experienced medical librarian from inception until January 27, 2023, in EBSCO CINAHL with Full Text, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection. Inclusion criteria included studies that involved adult patients (age≥18) who had a magnetic resonance imaging-confirmed TR and underwent a structured, supervised PT program of any length. All types of studies were included. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. A total of 1,491 studies were screened and 7 studies met inclusion criteria, 5 case studies and 2 cohort studies. All studies showed improvement or resolution of the TR with PT. Quantitative improvements were not noted in most studies and PT regimens were sparsely described. Overall quality assessment demonstrated 3 studies had “good,” 1 “fair,” and 3 “poor” quality evidence. Certainty of evidence was “low” due to risk of bias. A dedicated PT program may help to alleviate symptomatic TR; however due to limited evidence, risk of bias, and low certainty in evidence, the data is too weak to support a definite conclusion.

AbstractStudy abroad experiences are highly valuable as internationalization plays an increasingly important role in the higher education curriculum and business (Ghemawat & Bastian, 2017). Business schools have long recognized the value of the study abroad experience for both students and faculty (Black & Duhon, 2006). Given these conditions, one would expect best practices to be widely applied in the execution of short-term study abroad programs. Yet, this study’s review and analysis of faculty-led study abroad proposal guidelines did not find this to be the case. Content analysis was used on 396 pages of university faculty-led study abroad proposal guidelines from 19 randomly chosen universities in the United States to determine what best practices are being communicated to faculty. Our findings suggest that there is little evidence-based guidance on creating, planning, and executing a short-term faculty-led study abroad course. Building on this finding, we provide a review of the best practices literature and use this corpus to anchor a tutorial for designing a faculty-led study abroad course. These instructions provide business faculty with the information necessary to design a successful evidence-based short-term study abroad program.

This article documents endeavours to establish a higher education program for incarcerated learners in Aotearoa New Zealand. Presently, prisoners serving lengthy sentences in the country are precluded from obtaining a degree while in custody, which is in stark contrast to other jurisdictions with comparable penal systems. This study examines the challenges of implementing higher education programs in prisons in Aotearoa New Zealand and draws on the authors’ experiences to identify potential solutions. Two solutions were considered: a combined universities approach, which involved sharing the costs and efforts of creating a degree program for incarcerated learners among the country’s eight universities, and an instance of the Inside-Out Exchange program. However, both of these solutions were impeded by practical and logistical obstacles, including the arrival of the COVID-19 pandemic. Although the initiatives suggested in this study offer promising solutions to these challenges, their implementation has been hindered by practical and logistical difficulties. However, it is argued that it is imperative for policymakers and stakeholders to prioritise the establishment of sustainable and effective higher education programs in prisons, which have the potential to promote social equity and justice. To this end, the authors propose a single university applying for funding to establish and deliver higher education programs in prisons as a practical and viable solution. Policymakers and stakeholders are urged to take action towards realising this proposal, with a view towards creating a more equitable and just society.

This paper introduces the environmental model of mindfulness, a novel perspective that conceptualizes mindfulness as an adaptive set of cognitive styles influenced by specific socioecological contexts. Extending upon existing conceptualizations of mindfulness as a cultivated trait or practice, the environmental model describes how mindfulness can also result from cognitive adaptations to immediate-return environments. Through an interdisciplinary synthesis of cognitive psychology, anthropology, and environmental studies, four key factors are identified that foster mindful cognitive styles in immediate-return environments: immediate feedback, observational learning, nature exposure, and interconnected self-construal. By examining Indigenous communities living in immediate-return environments, this paper demonstrates how modern, delayed-return environments may inadvertently suppress innate mindful awareness, suggesting that mindfulness practices might be attempts to recalibrate toward more natural cognitive styles. The environmental model bridges Western medical and Eastern ethical perspectives on mindfulness, offering a unifying framework that acknowledges cognitive, environmental, and cultural influences. This approach not only enriches our understanding of human cognitive functioning but also broadens cultural perspectives on mindfulness, highlighting its manifestations across diverse sociocultural contexts. The model has profound implications for mindfulness research and interventions, providing a foundation for more ecologically valid and culturally sensitive approaches to fostering wellbeing. It invites a fundamental reconsideration of the relationship between human cognition and the environment, potentially revolutionizing our approach to mental health and cognitive enhancement in an increasingly complex world. This paper stands as a call to action for researchers, clinicians, and policymakers to rethink fundamental assumptions about human cognition and design environments that support our innate capacity for mindful awareness.

Abstract Background Efforts have been invested towards cessation of tobacco use among youths aged 18–35 years, however, motivators for continued tobacco smoking and reasons for quitting are limited in Ugandan settings. Therefore, this study aimed to explore motivations for continued tobacco smoking and reasons for quitting in Wakiso district Uganda. Methods This study used explanatory sequential method. Data from a Population-based survey collected from October 2019 to September 2020 was used to select participants for this qualitative study. Twenty-three in-depths interviews were conducted from July to October 2021 among youths (18-35years old) who reported continued tobacco use and those who quit. Data were analyzed using a team-based thematic content approach with the help of NVivo. Results Data was collected from a total of twenty three participants, fourteen were tobacco quitters and nine were current tobacco smokers. Recurrent habit, desire to complement the use of other drugs, peer pressure, using smoking as a replacement for alcohol consumption, low tobacco prices, smoking as a tradition were reported as motivators for continued tobacco smoking. However, reported reasons for quitting smoking by youths included; packaging health warnings, school based prevention programs, fear of associated health risks due to tobacco use, embarrassment from family members. Conclusion Targeted, and tailored tobacco prevention counselling through family support programs, intensified health education on the risks of smoking, and implementing stronger health warnings on tobacco packaging can be employed to reduce or stop tobacco use among urban youth.

Extant literature points to how the risk of discrimination is intrinsic to AI systems owing to the dependence on training data and the difficulty of post hoc algorithmic auditing. Transparency and auditability limitations are problematic both for companies’ prevention efforts and for government oversight, both in terms of how artificial intelligence (AI) systems function and how large‐scale digital platforms support recruitment processes. This article explores the risks and users’ understandings of discrimination when using AI and automated decision‐making (ADM) in worker recruitment. We rely on data in the form of 110 completed questionnaires with representatives from 10 of the 50 largest recruitment agencies in Sweden and representatives from 100 Swedish companies with more than 100 employees (“major employers”). In this study, we made use of an open definition of AI to accommodate differences in knowledge and opinion around how AI and ADM are understood by the respondents. The study shows a significant difference between direct and indirect AI and ADM use, which has implications for recruiters’ awareness of the potential for bias or discrimination in recruitment. All of those surveyed made use of large digital platforms like Facebook and LinkedIn for their recruitment, leading to concerns around transparency and accountability—not least because most respondents did not explicitly consider this to be AI or ADM use. We discuss the implications of direct and indirect use in recruitment in Sweden, primarily in terms of transparency and the allocation of accountability for bias and discrimination during recruitment processes.

Cooperation is widespread across life, but its existence can be threatened by exploitation. The rise of obligate social cheaters that are incapable of contributing to a necessary cooperative function can lead to the loss of that function. In the social amoeba Dictyostelium discoideum, obligate social cheaters cannot form dead stalk cells and in chimeras instead form living spore cells. This gives them a competitive advantage within chimeras. However, obligate cheaters of this kind have thus far not been found in nature, probably because they are often enough in clonal populations that they need to retain the ability to produce stalks. In this study we discovered an additional cost to obligate cheaters. Even when there are wild-type cells to parasitize, the chimeric fruiting bodies that result have shorter stalks and these are disadvantaged in spore dispersal. The inability of obligate cheaters to form fruiting bodies when they are on their own combined with the lower functionality of fruiting bodies when they are not represent limits on obligate social cheating as a strategy.

Land and water degradation caused by soil erosion and climate change pose major environmental threats, particularly in agricultural watersheds. Soil erosion in a catchment leads to low crop yields due to declining soil quality (SQ), productivity and sustainability. However, very few studies have been done to assess soil health in Kenya, and none in Narok County. Thus, the aim of this study was to evaluate the soil sustainability status in Kakia-Esamburmbur catchment, based on the identification of key indicators (IKI) from a large dataset (LDS) of 23 indicators, across three land use types designated as grass land (GL), crop land (CL) and forest land (FL). To achieve the stated objective, two soil quality indexing methods were employed: the Additive Soil Quality Index (A-SQI) using the LDS; and the Weighted Soil Quality Index (W-SQI) using Principal Component Analysis (PCA) as a reduction tool to obtain the IKI set. The results show that at a depth of 20 cm, the catchment's soils characteristics did not differ significantly. The two methods (A-SQI and W-SQI) resulted in FL having the highest SQI mean values (0.61, 0.57), followed by CL (0.59, 0.55), while the lowest SQI mean value was recorded in GL (0.58, 0.53). Additionally, the sensitivity analysis showed W-SQI as the most sensitive and superior method in the evaluation of SQI changes due to its high sensitivity and coefficient of variation (CV), at 2.25 and >12 %, respectively. Among the ten IKI, CEC made the greatest contribution to SQ (18.68 %), followed by BD (15.61 %), BIR (14.71 %), Mg (14.26 %), MBN (8.30 %), MBC (8.26 %), Sand (6.77 %), Moisture (5.75 %), TOC (5.16 %), and PMN (2.63 %). The findings show that the catchment belongs to the ''medium'' category of SQ. The IKI can help save time and reduce the cost of intensive lab works for temporal assessment and monitoring of the effects of different land use on SQ.

This editorial introduces our thematic issue, titled Examining New Models in Journalism Funding, at a pivotal time. While news companies have attempted to build sustainable business models, we have not yet seen a major leap forward. As observed by the authors of this issue, digital reader revenue has become a prominent source of income for many publishers, but the bulk of them continue to rely on advertising and print subscriptions for money. Recently, Google and Facebook have become major funders of news and innovation in journalism. Some governments have also launched specific support programs. After providing some background context, we introduce the articles featured in the issue. We go on to argue that these articles signal a renewed interest in the business of journalism, which will help us better understand the ongoing financial crisis in the commercial news sector at a more granular level.

Practitioners place importance on high-speed running (HSR) to monitor training practice and match-play demands, whilst attempting to maximise fitness and minimize the risk of injury occurrence. Practitioners apply various methods to quantify HSR, such as absolute thresholds, percentage of maximum sprint speed and maximal aerobic speed (MAS). A recent survey demonstrates the 5-minute run and 1200m shuttle test (ST) to be implemented among rugby league practitioners to quantify HSR by incorporating MAS. However, it is unclear as to how valid these methods are to accurately quantify MAS. Therefore, the aim of this study was to assess the validity of the 5-minute run and 1200m ST when compared to a gold standard measure for MAS. Twenty 1st team professional rugby league players competing in the European Super League participated in this study. Players were required to complete an incremental treadmill test, 5-minute run and 1200m ST over a two-week period in pre-season. MAS, peak heart rate (HRmax), peak lactate (Lapeak) and rating of perceived exertion (RPE) where collected upon completion of each test. Results demonstrated the 1200m ST to have a higher correlation for MAS than the 5-minute run (1200m ST: r = 0.73, 5-minute run: r = 0.64). However, when assessing validity using the level of agreement between data, the 5-minute run underreported MAS by 0.45 m·s-1 whereas the 1200m ST underreported MAS by 0.77 m·s-1. Ultimately, both field-based tests used in this study underreport MAS when compared to an incremental treadmill test, although the 5-minute run provides a closer agreement and therefore a more valid measurement for MAS than the 1200m ST.

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.

Abstract Background Patients on kidney replacement therapy (KRT) are vulnerable to severe illness from COVID-19. Timely, accurate surveillance is essential for planning and implementing infection control at local, regional and national levels. Our aim was to compare two methods of data collection for COVID-19 infections amongst KRT patients in England. Methods Adults receiving KRT in England were linked to two sources of data on positive COVID-19 tests recorded March-August 2020: (1) submissions from renal centres to the UK Renal Registry (UKRR) and (2) Public Health England (PHE) laboratory data. Patient characteristics, cumulative incidence by modality (in-centre haemodialysis (ICHD), home HD, peritoneal dialysis (PD) and transplant), and 28-day survival were compared between the two sources. Results 2,783/54,795 patients (5.1%) had a positive test in the combined UKRR-PHE dataset. Of these 2,783, 87% had positive tests in both datasets. Capture was consistently high for PHE (> 95% across modalities) but varied for UKRR (ranging from ICHD 95% to transplant 78%, p

Abstract Snow depth on sea ice is an Essential Climate Variable and a major source of uncertainty in satellite altimetry‐derived sea ice thickness. During winter of the MOSAiC Expedition, the “KuKa” dual‐frequency, fully polarized Ku‐ and Ka‐band radar was deployed in “stare” nadir‐looking mode to investigate the possibility of combining these two frequencies to retrieve snow depth. Three approaches were investigated: dual‐frequency, dual‐polarization and waveform shape, and compared to independent snow depth measurements. Novel dual‐polarization approaches yielded r2 values up to 0.77. Mean snow depths agreed within 1 cm, even for data sub‐banded to CryoSat‐2 SIRAL and SARAL AltiKa bandwidths. Snow depths from co‐polarized dual‐frequency approaches were at least a factor of four too small and had a r2 0.15 or lower. r2 for waveform shape techniques reached 0.72 but depths were underestimated. Snow depth retrievals using polarimetric information or waveform shape may therefore be possible from airborne/satellite radar altimeters.

Background Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting National Health Service trusts. Participants Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow–Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0–62.0 weeks) and 25.3 weeks (interquartile range 20.0–42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0–44.0 weeks) and 45.0 weeks (interquartile range 20.0–57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow–Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale – Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale – Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration This trial is registered as ISRCTN10133661. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information. Plain language summary Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients’ quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future. Scientific summary Background As people age, degenerative disease affects the intervertebral discs, facet joints and ligamentum flavum in the cervical spine. Consequently, the nerve root foramina may change shape and the nerve roots become compressed, causing a syndrome called cervical radiculopathy. Cervical radiculopathy is characterised by neck pain and cervical brachialgia, with the symptom of pain originating in the neck and radiating down into the upper arm. The reported incidence of cervical brachialgia is 1.79 cases per 1000 per year, with > 110,000 cases of brachialgia annually in the UK. Cervical brachialgia typically affects people aged 40–60 years, with up to 15% of patients unable to work because of the pain. In most patients, brachialgia is self-resolving with conservative management strategies. However, if symptoms persist 6 weeks to 3 months after onset, two of the available surgical techniques used (in the UK) to treat cervical brachialgia are posterior cervical foraminotomy (PCF) and anterior cervical discectomy (ACD). The most common and current standard operation is ACD, approaching from the front of the neck. The procedure is effective, but there is a high incidence of significant, potentially permanent, complications, including dysphagia and hoarse voice, which can be devastating to a patient’s quality of life. Alternatively, PCF can be undertaken from the back of the neck. Unlike ACD, PCF avoids risk to the structures in front of the spine including the carotid artery, sympathetic trunk, recurrent laryngeal nerve, larynx and pharynx, but may result in higher levels of postoperative neck pain and a greater need for revision surgery. Controversy therefore exists over which procedure is superior for the treatment of cervical brachialgia, and the decision on which procedure to use is frequently left to surgeon preference. The posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia (FORVAD) trial aimed to robustly compare the two procedures, with the ambition of providing definitive evidence that would guide surgical decision-making for patients with cervical brachialgia symptoms requiring surgical intervention. Objectives The primary objective of the trial was to determine whether PCF is superior to ACD in terms of improving clinical outcome, as measured by the Neck Disability Index (NDI) at 52 weeks post operation, among patients with persistent cervical brachialgia for whom conservative management has failed. The secondary objectives were comparison of the two surgeries in terms of NDI score, patient-reported neck and upper-limb pain, dysphagia and globus, hoarse voice symptoms, incidence of revision surgery, cost effectiveness over 52 weeks post operation, the extent and severity of a patient’s spinal cord functional impairment, and incidence of surgical complications up to 6 weeks post operation. The exploratory objectives were to explore the impact of variations in the optional surgical components of PCF (open or minimal-access surgery) and ACD (surgery with or without a plate) on NDI and EuroQol-5 Dimensions, three-level version (EQ-5D-3L) scores. Design The FORVAD trial was a UK multicentre, Phase III, parallel-group, superiority, individually randomised controlled trial comparing the clinical effectiveness and cost effectiveness of PCF with those of ACD among patients experiencing symptomatic unilateral cervical brachialgia for at least 6 weeks, with confirmed nerve root compression on magnetic resonance imaging or computerised tomography myelography. Neither participants nor medical or clinical trial staff in the FORVAD trial were blinded to the treatment allocated. The trial incorporated an internal pilot phase to assess the feasibility of trial delivery against prespecified recruitment criteria. Participants were randomised (1 : 1) to receive PCF or ACD via minimisation incorporating a random element, with minimisation factors of centre, duration of upper-limb symptoms and smoking status. Participants were followed up in clinic at day 1 and 6 weeks post operation, and by post at 12, 26, 39 and 52 weeks post operation. The target sample size was 252 participants (126 per trial arm). This number was required to have 90% power to detect the minimum clinically important difference of 10% (5 points) in the change in NDI score at 52 weeks post operation, assuming a between-patient standard deviation of 23 units, two-sided 5% significance level and 10% loss to follow-up. For the analysis of the primary outcome measure, it was intended to use a multilevel linear regression model incorporating random effects with respect to centre, and adjusting for baseline (day 0) NDI score and minimisation factors (duration of upper limb symptoms and smoking status). The statistical analysis plan was amended prior to final analysis of the data to account for the restricted sample size owing to the early closure of the trial and was limited to descriptive summaries. Setting The trial aimed to recruit from 15 NHS hospitals throughout the UK. Participating surgeons were expected to perform both trial procedures and were required to have performed a minimum of 10 of each surgical procedure and to have completed a bespoke training package on the e-brain platform [www.ebrain.net (accessed 25 April 2022)]. Participants Patients were eligible to participate if they had been diagnosed with unilateral cervical brachialgia that had persisted for at least 6 weeks, resultant from single-level nerve entrapment, and conservative management had previously failed. Patients with cervical myelopathy, spinal cord compression or who had previously had cervical spine surgery were excluded. Eligibility waivers were not granted in this trial. Interventions Pre-operative investigations and preparation were as per individual site protocol. Participants received either PCF or ACD. Minimal- and open-access techniques were permitted for PCF. For ACD, the choice of fusion material and the decision to use a plate were left to surgeon discretion. Postoperative care was also as per individual site protocol. Main outcome measures The primary outcome measure was the patient-reported percentage NDI score at 52 weeks post operation. Secondary patient-reported outcomes (collected at baseline; at days 1 and 6; and at 12, 26, 39 and 52 weeks post operation) were collected using the Numerical Rating Scale–Neck Pain (NRS-NP), the Numerical Rating Scale–Arm Pain (NRS-AP), the validated PainDETECT, the Eating Assessment Tool-10 items (EAT-10), the Glasgow–Edinburgh Throat Scale (GETS) and the Voice Handicap Index-10 items (VHI-10) tools. Secondary clinical outcomes included a restricted version of the American Spinal Injury Association (ASIA) assessment scale, intraoperative and postoperative complications, incidence of reoperations within 52 weeks of operation and assessment of hoarse voice from additional voice recordings collected from randomly selected participants using the grade, roughness, breathiness, asthenia and strain scoring system. Exploratory outcomes included whether participants receiving PCF received minimal- or open-access surgery, and whether participants receiving ACD received surgery with or without a plate. Patient-reported outcomes were recorded using the EQ-5D-3L, which, alongside collected health resource use data, informed cost-effectiveness analysis. Results Owing to slower than expected accrual, the trial closed to recruitment after randomising 23 participants, 14 to PCF and 9 to ACD, from 11 sites. Therefore, results from the trial should be interpreted with caution because of the small sample size. The median NDI scores at baseline and 52 weeks were 44.0 [interquartile range (IQR) 36.0–62.0] and 25.3 (IQR 20.0–42.0) in the PCF group, respectively, indicating a reduction (improvement) from baseline. In the ACD group, the median scores at baseline and 52 weeks were 35.6 (IQR 34.0–44.0) and 45.0 (IQR 20.0–57.0), respectively. Unlike the PCF group, NDI scores did not appear to improve from baseline in the ACD group. For the NRS-NP and NRS-AP, there was an initial increase from baseline in neck pain score on day 1 post operation in both groups [median 5.5 (IQR 4.0–8.0) at baseline to 8.5 (IQR 6.0–10.0) at 1 day post operation in the PCF group; median 5.0 (IQR 4.0–7.0) at baseline to 7.0 (IQR 4.0–9.0) at 1 day post operation in the ACD group]. Neck pain decreased after day 1 in both treatment groups; at 52 weeks, the median scores were 4.0 (IQR 2.0–5.0) in the PCF group and 5.0 (IQR 3.0–7.0) in the ACD group. In both groups, arm pain improved on day 1 [median 3.0 (IQR 2.0–8.0) in the PCF group; median 4.0 (IQR 0.5–5.0) in the ACD group] and reached its lowest level 12 weeks post operation [median 3.0 (IQR 2.0–8.0) in the PCF group; median 2.5 (IQR 0.0–5.0) in the ACD group]. Thereafter, arm pain deteriorated (increased), but remained below baseline [median 5.0 (IQR 2.0–7.0) in the PCF group and median 5.0 (IQR 3.0–6.0) in the ACD group at 52 weeks]. PainDETECT category scores fluctuated over the postoperative period in the PCF group, but reduced over time in the ACD group, suggesting that in the ACD group a higher proportion of the participants had developed nociceptive, rather than neuropathic, pain. The ASIA score remained unchanged in both treatment groups over the 6-week assessment period. For the EAT-10 and the VHI-10 outcomes, the ACD group had worse outcomes at day 1 [median EAT-10 scores of 0.0 (IQR 0.0–4.0) in the PCF group and 13.5 (IQR 3.5–16.0) in the ACD group, and median VHI-10 scores of 0.0 (IQR 0.0–2.0) in the PCF group and 2.0 (IQR 0.5–8.5) in the ACD group], after which the two groups are comparable. However, the median GETS score was worse in the ACD group postoperatively, although the IQRs in each treatment group overlap at all time points except day 1. Five postoperative complications were reported in five participants throughout the trial, all occurring in the ACD group. Reported complications included two instances of dysphagia and three ‘other’ complications: ‘wound infection’, ‘urinary retention’ and ‘wound redness stitches overnight’. No serious or unexpected serious complications, deaths or reoperations were reported. The health economics and qualitative study The revised aims of the cost-effectiveness analysis were to describe the costs of the surgical interventions, health-care service use and participant out-of-pocket expenditures, and the productivity costs of losses associated with the surgery and its consequences. Responses to the EQ-5D-3L questionnaire of generic health-related quality of life and the rate of data completion are summarised. All costs are based on 2019/20 prices and are presented without discounting, as the time horizon of the analysis is 52 weeks. The costs of the intervention were heavily influenced by outliers in the PCF group, resulting in mean health-care costs of initial surgery, including devices, operation and hospital stay, of £2745 [95% confidence interval (CI) £2344 to £3147] for the PCF group (n = 12) and £4295 (95% CI £3436 to £5154) for the ACD group (n = 8). The corresponding median costs were £2622 (IQR £2402–2824) for participants undergoing PCF and £4423 (IQR £3849–4821) for participants undergoing ACD. These costs were driven by the time in theatre, which was a mean of 30 minutes (median 45 minutes) shorter for PCF (mean 61 minutes, median 52 minutes, IQR 49–60 minutes) than for ACD (mean 91 minutes, median 100 minutes, IQR 75–109 minutes). Results aggregated up to week 6 are presented owing to high attrition thereafter. The mean costs from the NHS and Personal Social Services perspective were £2716 (95% CI £2345 to £3087) for the PCF group and £4133 (95% CI £3099 to £5167) for the ACD group; the median costs were £2634 (IQR £2444–2741) and £4214 (IQR £3602–4994) for the PCF and ACD groups, respectively. The mean per-patient costs to society were £4608 (95% CI £2514 to £6703) for the PCF group and £5015 (95% CI £2286 to £7743) for the ACD group; the median costs were £4097 (IQR £2448–6591) and £4143 (IQR £4126–4284) for the PCF and ACD groups, respectively. At baseline, severe problems with anxiety and depression were more common, and pain and discomfort according to the EQ-5D-3L classification system was more severe in the PCF group than in the ACD group, resulting in mean utility scores of 0.291 (95% CI 0.07 to 0.51) and 0.595 (95% CI 0.40 to 0.78) for PCF and ACD, respectively. The corresponding median scores were 0.210 (IQR –0.01 to 0.60) and 0.689 (IQR 0.66–0.69). This is likely to have played a role in the larger observed gains from baseline in postoperative EuroQol-5 Dimensions (EQ-5D) scores for participants in the PCF group than in the ACD group [median change at 6 weeks of 0.10 (IQR 0.00–0.13) and 0.02 (IQR –0.03 to 0.06), respectively]. A rapid qualitative study was conducted during trial close-down to understand the experiences of health-care professionals and participants who participated in the FORVAD trial and why recruitment had been challenging, with the aim of informing future research in this area. Semistructured interviews were conducted with 18 health-care professionals (research nurses and surgeons) and two participants who had participated in the FORVAD trial. Interviews explored participants’ experiences of the FORVAD trial and their reasons for taking part, and staff experiences of recruiting to the FORVAD trial and neurosurgery trials in general. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using rapid qualitative analysis. There was no single key factor that limited recruitment, and several themes were identified as common to all sites. Surgeons at participating sites supported the trial, and recognised collective clinical equipoise; however, many had preferences for one or the other procedure, linked to their usual practice. Organisation of the trial recruitment pathway varied, with some sites choosing to direct potentially eligible patients to dedicated clinics and other sites taking a more ad hoc approach. In the FORVAD trial, the dedicated clinic approach appeared to contribute to more eligible patients being identified and recruited, although staff at other sites explained that dedicated clinics did not fit easily with their clinical pathways. Randomisation on the day of surgery presented ethical and organisational challenges, and, where possible, should be avoided in future surgical trials. Organisation and implementation of a surgical trial in neurosurgery are complex and present many challenges. Future trials in neurosurgery should identify aspects of the protocol where it is possible to offer flexibility and ensure early multidisciplinary involvement at sites to maximise the effective integration of trial and clinical pathways. Conclusions The data suggest that PCF may be associated with better outcomes, fewer complications and lower cost, but the trial recruited slowly and was closed early. As a consequence, the trial is underpowered and definitive conclusions cannot be drawn. Trial recruitment was impaired by the lack of individual equipoise and concern about randomising on the day of surgery. A large prospective multicentre trial comparing ACD and PCF in the treatment of cervical brachialgia is still required. Trial registration This trial is registered as ISRCTN10133661. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

ABSTRACT: An artificial insemination (AI) company seeks to allocate semen units globally by balancing perceived demand with uncertain product supply, in what is an arduous subjective process. This study aimed to objectivize this process by providing a user-friendly linear programming model to allocate bulls' semen units to regions for the next trimester sales period based on maximum revenue, and to describe the features and outcomes of this model when applied to a sample bull herd and global demand scenario reflective of a leading AI company. The objective function of maximizing revenue was calculated by summing the product of units allocated by bull and region with purchase prices assigned by bull and region. Constraints considered were regional demand for overall units, regional preferences for specific genetic traits, bulls' production capacity, and percentage of bulls' units allocated to a single region. A sensitivity analysis was performed to identify the effects of variables and constraints on total revenue. Production, sales, and bull demographic data from 2018 to 2021 from a leading AI company were used to establish base values and build a sample herd of 61 bulls and 5 global regions. The case study provided a maximum revenue of $8,287,197 in semen sales per trimester, with 634,700 units allocated. Of the 61 bulls in the case study, 9 were not allocated to any region. The most limiting constraint was regional demand, which resulted in a surplus of 274,564 units not allocated. A sensitivity analysis confirmed this finding, with the largest shadow prices assigned to regional demands, and indicated that a single unit increase in regional demand would add up to $14.84 in total revenue.

Renal cell carcinoma (RCC) is increasing in incidence as more cross sectional imaging is performed with approximately 20%-30% of cases presenting with metastasis at the time of diagnosis. Small bowel metastatic disease is rare, with RCC to the small bowel being exceptionally rare. We present a case report of metastatic RCC that initially presented as upper gastrointestinal bleeding at time of diagnosis. We also provide a brief discussion of small bowel metastatic RCC disease and literature review.

Background: Ischemic heart disease (IHD) caused by the narrowing of coronary arteries is a major cause of morbidity and mortality worldwide. Clinical diagnosis involves complex, costly, and potentially invasive procedures. Objective: To address this problem, we introduce a novel clinical knowledge-enhanced machine learning (ML) pipeline to assist in timely and cost-effective IHD prediction. Methods: Unlike conventional data-driven “black box” ML approaches, we propose an effective mechanism to engage clinical expertise and gain insight into the “black box” at each stage of model development, including data analysis, preprocessing, selecting the most clinically discriminative features, and model evaluation. One-hot feature encoding is introduced to expose hidden bias and highlight the important elements and features. Results: Experimental results on the benchmark Cleveland IHD dataset showed that the proposed clinical knowledge–enhanced ML pipeline overperformed state-of-the-art data-driven ML models, using even fewer features. Our model based on one-hot feature encoding and support vector machine achieved the best accuracy of 94.4% and sensitivity 95% by using only 7 discriminative attributes. Conclusion: We share insights and discuss the effectiveness of incorporating clinical input in machine learning to improve model performance, as well as addressing some practical issues such as data bias and interpretability. We hope this preliminary study on engaging clinical expertise to explore the “black box” would improve the trustworthiness of AI and its potential wider uptake in the medical field.

Abstract We performed a high-throughput phenotypic whole cell screen of Mycobacterium tuberculosis against a diverse chemical library of approximately 100,000 compounds from the AbbVie corporate collection and identified 24 chemotypes with anti-tubercular activity. We selected two series for further exploration and conducted structure–activity relationship studies with new analogs for the 4-phenyl piperidines (4PP) and phenylcyclobutane carboxamides (PCB). Strains with mutations in MmpL3 demonstrated resistance to both compound series. We isolated resistant mutants for the two series and found mutations in MmpL3. These data suggest that MmpL3 is the target, or mechanism of resistance for both series.

Mutations in HNRNPH2 cause an X-linked neurodevelopmental disorder with features that include developmental delay, motor function deficits, and seizures. More than 90% of patients with hnRNPH2 have a missense mutation within or adjacent to the nuclear localization signal (NLS) of hnRNPH2. Here, we report that hnRNPH2 NLS mutations caused reduced interaction with the nuclear transport receptor Kapβ2 and resulted in modest cytoplasmic accumulation of hnRNPH2. We generated 2 knockin mouse models with human-equivalent mutations in Hnrnph2 as well as Hnrnph2-KO mice. Knockin mice recapitulated clinical features of the human disorder, including reduced survival in male mice, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures. In contrast, 2 independent lines of Hnrnph2-KO mice showed no detectable phenotypes. Notably, KO mice had upregulated expression of Hnrnph1, a paralog of Hnrnph2, whereas knockin mice failed to upregulate Hnrnph1. Thus, genetic compensation by Hnrnph1 may counteract the loss of hnRNPH2. These findings suggest that HNRNPH2-related disorder may be driven by a toxic gain of function or a complex loss of HNRNPH2 function with impaired compensation by HNRNPH1. The knockin mice described here are an important resource for preclinical studies to assess the therapeutic benefit of gene replacement or knockdown of mutant hnRNPH2.

BackgroundAsthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. ObjectiveThe primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. MethodsBOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. ResultsThe last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. ConclusionsWe will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. International Registered Report Identifier (IRRID)DERR1-10.2196/46741

Abstract Background Pain is one of the most common complaints that patients present to the emergency department for; emergency medicine providers are tasked with providing appropriate pain relief while simultaneously limiting the risk of personal and societal harm that may result from opioid misuse. The Lakeland Regional Medical Center developed a medical management program that identified frequent emergency department visitors with a chief complaint of pain. Individualized care plans were developed for these patients. A retrospective review was then conducted to assess the efficacy of these care plans in reducing the number of emergency department visits for pain-related complaints by the patients entered into the medical management program. Results There were 294 patients; 65% were male, and the median age was 41 (interquartile range: 33 to 51). A total of 80% percent of the patients were white, and the payors were as follows: 53% were self-pay, 42% were government programs, and 5% had private insurance. The three most common chronic pain complaints were 39% abdominal pain, 24% back/neck pain, and 23% headache/migraine (patients could have more than one area of pain). A total of 60% of the patients had a primary care provider, and another 18% had a pain management provider in addition to primary care. Post plan admissions were significantly reduced to a median of 1 (IQR 0 to 3) with the Wilcoxon signed-rank test’s p-value of less than 0.001. Conclusion The authors describe their experience with a quality improvement initiative that identifies frequent emergency department visitors with a chief complaint of pain and provides individualized care plans to these patients. The goals of the program are to improve patient’s quality and consistency of care, through interventions that eliminate the prescribing of opioids while providing non-opioid alternatives.

Abstract Knowing the distribution of fish larvae can inform fisheries science and resource management in several ways, by: 1) providing information on spawning areas; 2) identifying key areas to manage and conserve; and 3) helping to understand how fish populations are affected by anthropogenic pressures, such as overfishing and climate change. With the expansion of industrial fishing activity after 1945, there was increased sampling of fish larvae to help better understand variation in fish stocks. However, large-scale larval records are rare and often unavailable. Here we digitize data from Nishikawa et al. (1985), which were collected from 1956–1981 and are near-global (50°N–50°S), seasonal distribution maps of fish larvae of 18 mainly commercial pelagic taxa of the families Scombridae, Xiphiidae, Istiophoridae, Scombrolabracidae, and Scomberesocidae. Data were collected from the Pacific, Atlantic, and Indian Oceans. We present four seasonal 1° × 1° resolution maps per taxa representing larval abundance per grid cell and highlight some of the main patterns. Data are made available as delimited text, raster, and vector files.

Abstract The frequent use of insecticides to manage soybean aphids, Aphis glycines (Hemiptera: Aphididae), in the United States has contributed to field-evolved resistance. Pyrethroid-resistant aphids have nonsynonymous mutations in the voltage-gated sodium channel (vgsc). We identified a leucine to phenylalanine mutation at position 1014 (L1014F) and a methionine to isoleucine mutation (M918I) of the A. glycines vgsc, both suspected of conferring knockdown resistance (kdr) to lambda-cyhalothrin. We developed molecular markers to identify these mutations in insecticide-resistant aphids. We determined that A. glycines which survived exposure to a diagnostic concentration of lambda-cyhalothrin and bifenthrin via glass-vial bioassays had these mutations, and showed significant changes in the resistance allele frequency between samples collected before and after field application of lambda-cyhalothrin. Thus, a strong association was revealed between aphids with L1014F and M918I vgsc mutations and survival following exposure to pyrethroids. Specifically, the highest survival was observed for aphids with the kdr (L1014F) and heterozygote super-kdr (L1014F + M918I) genotypes following laboratory bioassays and in-field application of lambda-cyhalothrin. These genetic markers could be used as a diagnostic tool for detecting insecticide-resistant A. glycines and monitoring the geographic distribution of pyrethroid resistance. We discuss how generating these types of data could improve our efforts to mitigate the effects of pyrethroid resistance on crop production.

Background: Acne vulgaris is a common cutaneous disorder. Diet and metabolism, specifically glycemic content and dairy, influence hormones such as insulin, insulin-like growth factor 1, and androgens, which affect acnegenesis. Objective: To systematically review high-quality evidence regarding the association of dietary glycemic and dairy intake with acnegenesis. Methods: A comprehensive literature search, without timeline restriction, of MEDLINE (completed between October and November 2021) for English-language papers that examined the association between diet and acne was conducted. The evidence quality was assessed using the Ottawa quality assessment scale. Results: The literature search yielded 410 articles, of which 34 articles met the inclusion criteria. The literature on whether dairy product intake is associated with acnegenesis is mixed and may be dependent on sex, ethnicity, and cultural dietary habits. High glycemic index and increased daily glycemic load intake were positively associated with acnegenesis and acne severity, an observation supported by randomized controlled trials. Conclusion: High glycemic index, increased glycemic load, and carbohydrate intake have a modest yet significant proacnegenic effect. Increased dairy consumption may have been proacnegenic in select populations, such as those in which a Western diet is prevalent. The impact of diet on acnegenesis is likely dependent on sex and ethnicity. Further randomized trials are necessary to fully characterize the potential associations.

Abstract Animal models have been invaluable in the identification of molecular events occurring in and contributing to intervertebral disc (IVD) degeneration and important therapeutic targets have been identified. Some outstanding animal models (murine, ovine, chondrodystrophoid canine) have been identified with their own strengths and weaknesses. The llama/alpaca, horse and kangaroo have emerged as new large species for IVD studies, and only time will tell if they will surpass the utility of existing models. The complexity of IVD degeneration poses difficulties in the selection of the most appropriate molecular target of many potential candidates, to focus on in the formulation of strategies to effect disc repair and regeneration. It may well be that many therapeutic objectives should be targeted simultaneously to effect a favorable outcome in human IVD degeneration. Use of animal models in isolation will not allow resolution of this complex issue and a paradigm shift and adoption of new methodologies is required to provide the next step forward in the determination of an effective repairative strategy for the IVD. AI has improved the accuracy and assessment of spinal imaging supporting clinical diagnostics and research efforts to better understand IVD degeneration and its treatment. Implementation of AI in the evaluation of histology data has improved the usefulness of a popular murine IVD model and could also be used in an ovine histopathological grading scheme that has been used to quantify degenerative IVD changes and stem cell mediated regeneration. These models are also attractive candidates for the evaluation of novel anti‐oxidant compounds that counter inflammatory conditions in degenerate IVDs and promote IVD regeneration. Some of these compounds also have pain‐relieving properties. AI has facilitated development of facial recognition pain assessment in animal IVD models offering the possibility of correlating the potential pain alleviating properties of some of these compounds with IVD regeneration.

Abstract The purpose of this review was to evaluate data generated by animal models of intervertebral disc (IVD) degeneration published in the last decade and show how this has made invaluable contributions to the identification of molecular events occurring in and contributing to pain generation. IVD degeneration and associated spinal pain is a complex multifactorial process, its complexity poses difficulties in the selection of the most appropriate therapeutic target to focus on of many potential candidates in the formulation of strategies to alleviate pain perception and to effect disc repair and regeneration and the prevention of associated neuropathic and nociceptive pain. Nerve ingrowth and increased numbers of nociceptors and mechanoreceptors in the degenerate IVD are mechanically stimulated in the biomechanically incompetent abnormally loaded degenerate IVD leading to increased generation of low back pain. Maintenance of a healthy IVD is, thus, an important preventative measure that warrants further investigation to preclude the generation of low back pain. Recent studies with growth and differentiation factor 6 in IVD puncture and multi‐level IVD degeneration models and a rat xenograft radiculopathy pain model have shown it has considerable potential in the prevention of further deterioration in degenerate IVDs, has regenerative properties that promote recovery of normal IVD architectural functional organization and inhibits the generation of inflammatory mediators that lead to disc degeneration and the generation of low back pain. Human clinical trials are warranted and eagerly anticipated with this compound to assess its efficacy in the treatment of IVD degeneration and the prevention of the generation of low back pain.

Modern vehicles rely on data from a vast array of sensors such as radar and GPS equipment that can be shared with surrounding vehicles and other interested parties. Vehicle-to-everything (V2X) is the collection of systems that enable such communication. Although this data sharing has the potential to improve both the safety and efficiency of vehicles, ensuring that what is shared has not been altered, deleted, forged, leaked, or otherwise tampered with remains a challenging problem. Today, blockchain technology allows a system’s participants to come to an agreement (consensus) on the state of the system and its data in a decentralized, trustless manner. This new technology may be capable of securing V2X data, as well as enabling other useful V2X services such as payments. However, the V2X ecosystem poses several unique challenges that complicate the application of blockchain technology, not least of which is the vast number of communications that any proposed blockchain network will need to support. This paper gives an overview of V2X and blockchain technology, explores potential applications of blockchain within the V2X domain, and justifies its importance. It also reviews, analyzes, and discusses various blockchain architectures that could support V2X applications. Though there is a place for blockchain in the V2X environment, currently there is no robust or mature blockchain architecture available that could support the entire ecosystem’s needs. As such, this paper proposes novel directions for future research towards the creation of such a blockchain.

Background and aimIn acute severe COVID-19, patients present with lung inflammation and vascular injury, accompanied by an exaggerated cytokine response. In this study, our aim was to describe the inflammatory and vascular mediator profiles in patients who were previously hospitalized with COVID-19 pneumonitis, months after their recovery, and compare them with those in patients recovering from severe sepsis and in healthy controls.MethodsA total of 27 different cytokine, chemokine, vascular endothelial injury and angiogenic mediators were measured in the plasma of forty-nine patients 5.0 ± 1.9 (mean ± SD) months after they were hospitalized with COVID-19 pneumonia, eleven patients 5.4 ± 2.9 months after hospitalization with acute severe sepsis, and 18 healthy controls.ResultsCompared with healthy controls, IL-6, TNFα, SAA, CRP, Tie-2, Flt1, and PIGF were significantly increased in the post-COVID group, and IL-7 and bFGF were significantly reduced. While IL-6, PIGF, and CRP were also significantly elevated in post-Sepsis patients compared to controls, the observed differences in TNFα, Tie-2, Flt-1, IL-7 and bFGF were unique to the post-COVID group. TNFα levels significantly correlated with the severity of acute COVID-19 illness (spearman’s r = 0.30, p < 0.05). Furthermore, in post-COVID patients, IL-6 and CRP were each strongly negatively correlated with gas transfer factor %predicted (spearman’s r = –0.51 and r = –0.57, respectively, p < 0.002) and positively correlated with computed tomography (CT) abnormality scores at recovery (r = 0.28 and r = 0.46, p < 0.05, respectively).ConclusionA unique inflammatory and vascular endothelial damage mediator signature is found in plasma months following acute COVID-19 infection. Further research is required to determine its pathophysiological and clinical significance.

Mapping and monitoring cluster morphology provides insights for disease risk assessment, quality control in wine production, and understanding environmental influences on cluster shape. During the progression of grapevine morphology, cluster closure (CC) (also called bunch closure) is the stage when berries touch one another. This study used mobile phone images to develop a direct quantification method for tracking CC in three grapevine cultivars (Riesling, Pinot gris, and Cabernet Franc). A total of 809 cluster images from fruit set to veraison were analyzed using two image segmentation methods: (i) a Pyramid Scene Parsing Network (PSPNet) to extract cluster boundaries and (ii) Otsu’s image thresholding method to calculate % CC based on gaps between the berries. PSPNet produced high accuracy (mean accuracy = 0.98, mean intersection over union (mIoU) = 0.95) with mIoU > 0.90 for both cluster and noncluster classes. Otsu’s thresholding method resulted in

Recently, football has seen the creation of various novel, ubiquitous metrics used throughout clubs' analytics departments. These can influence many of their day-to-day operations ranging from financial decisions on player transfers, to evaluation of team performance. At the forefront of this scientific movement is the metric expected goals, a measure which allows analysts to quantify how likely a given shot is to result in a goal however, xG models have not until this point considered using important features, e.g., player/team ability and psychological effects, and is not widely trusted by everyone in the wider football community. This study aims to solve both these issues through the implementation of machine learning techniques by, modelling expected goals values using previously untested features and comparing the predictive ability of traditional statistics against this newly developed metric. Error values from the expected goals models built in this work were shown to be competitive with optimal values from other papers, and some of the features added in this study were revealed to have a significant impact on expected goals model outputs. Secondly, not only was expected goals found to be a superior predictor of a football team's future success when compared to traditional statistics, but also our results outperformed those collected from an industry leader in the same area.

BackgroundFrailty in older adults has been associated with reduced brain health. However, structural brain signatures of frailty remain understudied. Our aims were: (1) Explore associations between a frailty index (FI) and brain structure on magnetic resonance imaging (MRI). (2) Identify the most important FI features driving the associations.MethodsWe designed a cross-sectional observational study from a population-based study (The Irish Longitudinal Study on Aging: TILDA). Participants aged ≥50 years who underwent the wave 3 MRI sub-study were included. We measured cortex, basal ganglia, and each of the Desikan-Killiany regional volumes. Age-and sex-adjusted correlations were performed with a 32-item self-reported FI that included conditions commonly tested for frailty in research and clinical settings. A graph theory analysis of the network composed by each FI item and cortex volume was performed. White matter fiber integrity was quantified using diffusion tensor imaging (DTI).ResultsIn 523 participants (mean age 69, 49% men), lower cortex and thalamic volumes were independently associated with higher FI. Sensory and functional difficulties, diabetes, polypharmacy, knee pain, and self-reported health were the main FI associations with cortex volume. In the network analysis, cortex volume had a modest influence within the frailty network. Regionally, higher FI was significantly associated with lower volumes in both orbitofrontal and temporal cortices. DTI analyses revealed inverse associations between the FI and the integrity of some association bundles.ConclusionThe FI used had a recognizable but subtle structural brain signature in this sample. Only some FI deficits were directly associated with cortex volume, suggesting scope for developing FIs that include metrics more specifically related with brain health in future aging neuroscience studies.

Primary and disseminated lymphoma of the female reproductive tract are rare types of lymphoma. However, in the setting of solid organ transplant, recipients have an approximately doubled risk of acquiring and dying from malignancy. Multiple treatment modalities are available for post-transplant lymphoproliferative diseases (PTLD), including chemotherapy, radiotherapy, surgery, and immunosuppression radiotherapy. We report a case of a 61-year-old female with multifocal nodal diffuse large B-cell lymphoma and a history of a renal transplant secondary to IgA nephropathy who developed metastatic diffuse large B-cell lymphoma to the uterus. While the baseline incidence of PTLD is elevated when compared with lymphoma in the general population, metastatic uterine lymphoma is rare. Awareness of reproductive organ involvement by lymphomas and increased malignancy risk in organ transplant patients are important considerations for diagnostic evaluation, including radiologic assessment.

For many privacy scholars, consent is on life support, if not dead. In July 2020, we held six focus groups in Australia to test this claim by gauging attitudes to consent and privacy, with a spotlight on smartphones. These focus groups included discussion of four case studies: ‘shadow profiles’, eavesdropping by companies on smartphone users, non-consensual government surveillance of its citizens and contact tracing apps developed to combat COVID-19. Our participants expressed concerns about these practices and said they valued individual consent and saw it as a key element of privacy protection. However, they saw the limits of individual consent, saying that the law and the design of digital services also have key roles to play. Building on these findings, we argue for a blend of good law, good design and an appreciation that individual consent is still valued and must be fixed rather than discarded - ideally in ways that are also collective. In other words, consent is dead; long live consent.

Abstract Fusion is the current standard of care for AIS. Anterior vertebral body tethering (AVBT) is a motion-sparing alternative gaining interest. As a novel procedure, there is a paucity of literature on safety. Here, we report 90-day complication rates in 184 patients who underwent AVBT by a single surgeon. Patients were retrospectively reviewed. Approaches included 71 thoracic, 45 thoracolumbar, 68 double. Major complications were those requiring readmittance or reoperation, prolonged use of invasive materials such as chest tubes, or resulted in spinal cord or nerve root injury. Minor complications resolved without invasive intervention. Mean operative time and blood loss were 186.5 ± 60.3 min and 167.2 ± 105.0 ml, respectively. No patient required allogenic blood transfusion. 6 patients experienced major (3.3%), and 6 had minor complications (3.3%). Major complications included 3 chylothoracies, 2 hemothoracies, and 1 lumbar radiculopathy secondary to screw placement requiring re-operation. Minor complications included 1 patient with respiratory distress requiring supplementary oxygen, 1 superficial wound infection, 2 cases of prolonged nausea, and 1 Raynaud phenomenon. In 184 patients who underwent AVBT for AIS, major and minor complication rates were both 3.3%.

The teaching relation has always been a puzzle. Some take education as the passing on and acquisition of information. They regard the lecture format as crucial. Others see it in terms of developing the reasoning ability of students. In seminars and conversations, they strive to have their students reflect and learn to “think for themselves.” Their goal is a rational individual capable of insight. Levinas, the French Philosopher, who famously positioned ethics as first philosophy, i.e., as determinative of how we think of ourselves and our world, advances a novel view, one springing from the “face to face” relation. In this article, we explore how his understanding of this relation leads to his situating education in an ethical context.

Category: Ankle Arthritis; Ankle; Diabetes Introduction/Purpose: Total ankle replacement (TAR) has achieved relatively successful outcomes with respect to postoperative complications; however, mixed evidence exists regarding early complication rates, reoperation, and infection 1-5 . The largest study of TAR to date indicates a statistically significant risk of postoperative infection in tobacco users and diabetic patients 6 . Unlike currently established anterior approaches to arthroplasty, the lateral transfibular approach potentially avoids disruption of perfusion to the skin, possibly decreasing postoperative complications 7 . The lateral ankle allows surgeons to correct malunion of the fibula in post-traumatic arthritis deformity cases and achieve appropriate coronal and sagittal implant alignment to achieve similar physiological joint orientation 8,9 . The purpose of this study was to report 90-day reoperation and wound complication rates in lateral approach to total ankle replacement for post-traumatic arthritis (PTA). Methods: A retrospective chart review of lateral TAR cases from 2016-2022 was conducted at a single institution. Only patients undergoing TAR for post-traumatic arthritis were included in this review. A total of 49 patients (22 females and 27 males) underwent total ankle replacement with the Zimmer Biomet Trabecular Metal TM Total Ankle by a single surgeon. Patient demographics, operative data, complications, and adverse events requiring corrective surgery were recorded within 90 days of arthroplasty. Results: The patient sample included 6 active smokers, 11 diabetics, and 32 patients with hypertension with an average age of 60.7 and average BMI of 34.3 (Table 1). Three of the 49 (6.1%) patients required secondary surgery within 3 months of surgery (Table 2). Revision surgery indications included: 1 (2.0%) for removing painful hardware, 2 (4.1%) due to infection, and 1 (2.0%) for tarsal tunnel syndrome after surgery. There were 0 nonunions of the fibula at 90 days and through 1 year follow up. Of the patients requiring secondary surgery for infection, 1 was a smoker and 1 had a history of ankle fusion nonunion and avascular necrosis which was converted to a TAR (Table 4). Conclusion: This retrospective study demonstrates a comparable rate of secondary surgeries following TAR via lateral approach in the early postoperative period (6.1%) while having a slightly higher rate of infection than those previously reported (4.1%)7,8. Notwithstanding, we observed a 100% healing rate of fibula osteotomies; however, we failed to demonstrate a lower incidence of wound complications than previously reported. Surgeons should counsel patients of these risks in those with PTA undergoing lateral TAR, especially in smokers and diabetics.

Category: Trauma; Ankle; Sports; Other Introduction/Purpose: Increasing overlap exists between surgical care provided by orthopedic foot and ankle surgeons and podiatrists. Use of either specialty depends on numerous factors including perceived costs. Unfortunately, large scale cost comparisons between the two are lacking. Such data is increasingly important given the current climate of payment reform and cost containment in healthcare. Using national Medicare claims data, we therefore aimed to compare per-case Medicare payments between orthopedic foot and ankle surgeons and podiatrists for ankle fracture fixation. We additionally aimed to describe any differences between groups that may drive differences in payments. Methods: This IRB-exempt retrospective study included patients undergoing either unimalleolar, bimalleolar, or trimalleolar ankle fracture repair as recorded in the national Medicare Limited Data Set (2013-2019). Type of surgeon (orthopedic foot and ankle surgeon or podiatric surgeon) was determined using publicly available healthcare provider taxonomy information available from the Washington Publishing Company ( www.wpc-edi.com ) and maintained by the National Uniform Claim Committee ( www.nucc.org ); crosswalks between Medicare Specialty Code and Provider Taxonomy are publicly available. The primary outcome was total Medicare payments specific to the procedure, as a surrogate for cost (inflation-adjusted to 2019 US dollars). Additionally, patient demographics and hospital characteristics were compared between groups to determine if any specific factors associated with costs may influence group differences. Univariable tests (chi-squared and t-tests; non-parametric tests where appropriate) assessed significance of group differences. Results: Overall, 16,927 unimalleolar; 17,244 bimalleolar; and 11,717 trimalleolar fracture repairs were included. Of these, orthopedic surgeons performed more procedures than podiatrists (86.7% vs 13.3% for uni-; 92.4% and 7.6% for bi-; 92.2% and 7.8% for trimalleolar fracture repairs respectively). The mean and median age (71.6 - 72.7 [70-71] years) as well as the mean and median Charlson-Deyo Comorbidity Index (0.6 - 0.7 [0]) did not significantly differ between patients treated by an orthopedic surgeon or podiatrist (p = 0.157 and p = 0.890 respectively). Regionally, podiatrists saw patients more often in the West and Midwest whereas providers in the South were more often orthopedic surgeons (p < 0.001). Median procedure-specific Medicare payments for all three categories of ankle fracture repairs were significantly lower for orthopedic surgeons compared to podiatrists: $4,156 vs $4,300 for uni-, $4,205 vs $4,379 for bi-, and $4,396 vs $4,525 for trimalleolar, respectively (all p < 0.001). Conclusion: In this analysis comparing Medicare payments between orthopedic foot and ankle surgeons and podiatrists we found that ankle fracture fixation procedures performed by the orthopedic surgeons were less expensive and that cost differences do not appear to be driven by patient characteristics. Additionally, we were able to discern geographic differences regarding practice location of both surgeon types. These data will inform future discussions on how to optimize costs of foot and ankle surgical care.