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Background: The Irish Out-of-Hospital Cardiac Arrest registry (OHCAR) collects data based on the internationally recognised Utstein template. The Utstein comparator group (bystander witnessed and initial shockable rhythm) has specific relevance in benchmarking out-of-hospital cardiac arrest (OHCA) health system performance. Aims: To describe OHCA in the Utstein comparator group during 2012 to 2020 in Ireland. To explore predictors of bystander CPR, defibrillation, and survival to hospital discharge. Methods: National level OHCA registry data were interrogated. The subset of patients in the Utstein comparator group were identified and explored. Multivariable logistic regression was used to model outcome predictors. Results: There were 3,092 cases of OHCA in the Utstein comparator group during 2012 to 2020. Overall survival to hospital discharge was 27%. On average there were yearly improvements in bystander CPR, bystander defibrillation, and survival. Bystander CPR was associated with a 57% increase, while bystander defibrillation was associated with a 78% increase in the adjusted odds of survival to hospital discharge. The adjusted odds of both bystander CPR and defibrillation were higher in rural areas, despite decreased survival in these communities when compared to urban. OHCA that occurred at home was associated with decreased odds of bystander CPR, bystander defibrillation, and survival to hospital discharge. Conclusions: Bystander CPR, bystander defibrillation and survival to hospital discharge have increased in the Utstein comparator group during 2012–2020 in Ireland. Bystander CPR and defibrillation remain key modifiable health systems targets to increase overall OHCA survival.

Purpose: A primary challenge in clinical genetics is accurate interpretation of identified variants and relaying the information to patients and providers. Inconsistencies around handling variant reclassifications and notifying patients, combined with the lack of prescriptive guidelines on re-evaluation, reanalysis, and return of variants, has created practice challenges. Although relevant empirical work has emerged, the scope and outcomes of this research have not been characterized. Methods: We conducted a systematic literature review of variant reclassification and recontact research (2013-2023) across subdisciplines of medical genetics. Of the 159 nonduplicate records screened, we summarize findings from 54 included research articles describing variant reclassification frequencies, outcomes, and stakeholder perspectives on recontact. Results: The included articles reported on active reclassification (n = 20), passive reclassification (n = 13), stakeholder surveys (n = 11), qualitative interviews (n = 7), and reanalysis of published or ClinVar data (n = 3). On average, active and passive approaches yielded different reclassification frequencies—31% and 20%, respectively, which were considerably higher than ClinVar (

AreTomo, an abbreviation for Alignment and Reconstruction for Electron Tomography, is a GPU accelerated software package that fully automates motion-corrected marker-free tomographic alignment and reconstruction in a single package. By correcting in-plane rotation, translation, and importantly, the local motion resulting from beam-induced motion from tilt to tilt, AreTomo can produce tomograms with sufficient accuracy to be directly used for subtomogram averaging. Another major application is the on-the-fly reconstruction of tomograms in parallel with tilt series collection to provide users with real-time feedback of sample quality allowing users to make any necessary adjustments of collection parameters. Here, the multiple alignment algorithms implemented in AreTomo are described and the local motions measured on a typical tilt series are analyzed. The residual local motion after correction for global motion was found in the range of ± 80 Å, indicating that the accurate correction of local motion is critical for high-resolution cryo-electron tomography (cryoET).

Deposition of tau aggregates in the brain is a pathological hallmark of several neurodegenerative diseases, termed tauopathies, such as Alzheimer's disease (AD), corticobasal degeneration, and progressive supranuclear palsy (PSP). As transcellular spread of pathological tau aggregates has been implicated in disease progression, immunotherapy is being considered as a treatment for tauopathies. Here we report a detailed biochemical and biophysical characterization of the tau-binding properties of gosuranemab, a humanized monoclonal antibody directed against N-terminal tau that is currently being investigated as a treatment for AD. Binding experiments showed that gosuranemab exhibited high affinity for tau monomer, tau fibrils, and insoluble tau from different tauopathies. Epitope mapping studies conducted using X-ray crystallography and mutagenesis showed that gosuranemab bound to human tau residues 15–22. Immunodepletion of pathological human brain homogenates and transgenic mouse interstitial fluid (ISF) with gosuranemab resulted in reduced tau aggregation in tau biosensor cells. Preincubation of seed-competent AD-tau with gosuranemab significantly inhibited tau aggregation in mouse primary cortical neurons. Gosuranemab also significantly reduced unbound N-terminal tau in cerebrospinal fluid (CSF) from individuals with PSP and AD, and in ISF and CSF of treated transgenic mice. These results are consistent with the >90% target engagement observed in the CSF of some clinical trial dosing cohorts and support the evaluation of gosuranemab as a potential treatment for AD.

Summary: Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

Background: Whole slide digital imaging (WSDI) offers an alternative to glass slides for diagnostic interpretation. While prior work has concentrated on the use of whole slide digital imaging for routine diagnostic cases, this study focuses on diagnostic interpretation of digital images for a highly challenging area, upper gastro-intestinal (GI) dysplasia. The aim of this study is to study the accuracy and efficiency of WSDI in the diagnosis of upper GI tract dysplasia. Materials and Methods: Forty-two hematoxylin and eosin (H and E)-stained slides representing negative, indefinite, low grade and high grade dysplasia were selected and scanned at 20x (Aperio XT). Four attending GI pathologists reviewed the WSDI, then glass slides, with at least 3-4 weeks between each media; glass slides were re-reviewed 16-18 months later. Results: Intraobserver variability for three clinically relevant categories (negative, indefinite/low grade, high grade) was wider for WSDI to glass (kappa range 0.36-0.78) than glass to glass (kappa range 0.58-0.75). In comparison to glass slide review, WSDI review required more time and was associated with an unexpected trend toward downgrading dysplasia. Conclusions: Our results suggest: (1) upper GI dysplasia can be diagnosed using WSDI with similar intraobserver reproducibility as for glass slides; however, this is not true for all pathologists; (2) pathologists may have a tendency to downgrade dysplasia in digital images; and (3) pathologists who use WSDI for interpretation of GI dysplasia cases may benefit from regular, on-going, re-review of paired digital and glass images to ensure the most accurate utilization of digital technology, at least in the early stages of implementation.

Impaired wound healing is a significant concern for humans in space, where the unique microgravity environment poses challenges to the natural healing processes of the body. Similar to chronic wounds on earth, such as diabetic foot ulcers and venous leg ulcers, wounds inflicted in space exhibit delayed or impaired healing responses. These wounds share common features, including dysregulated cellular signaling, altered cytokine profiles, and impaired tissue regeneration. Little is known about the mechanisms underlying wound healing under microgravity. In this review, we focused on exploring the parallels between wound healing in space and chronic wounds on earth as a fundamental approach for developing effective countermeasures to promote healing and mitigate associated health risks during long-space missions., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In city hospitals, subway-related traumatic amputations are a frequent pattern of injury, however there is a paucity of literature on this specific injury pattern. The purpose of this study was to describe the epidemiology of subway-related traumatic amputations, as well as compare them to non-subway traumatic amputations., Patients and Methods: Retrospective review was performed at a single Level-1 trauma center in a metropolitan area. All patients who sustained a traumatic lower-extremity amputation over a seven-year period were included. Demographics, injury, treatment-related information, and complications were collected. Subway and non-subway traumatic amputations were statistically compared. Cohorts were further subdivided into above-knee amputations (AKAs) and below-knee amputations (BKAs) for statistical comparison., Results: Fifty-seven patients sustained 72 traumatic lower-extremity amputations, including 64 subway-related amputations. Fifteen patients with bilateral lower-extremity amputations all had subway-related injuries. Patients with subway-related injuries were more likely to have a history of alcohol use disorder (58.1 % vs. 0 %; P = 0.002), and experienced longer stays in the intensive care unit (ICU) (8.9 vs. 3.6 days; P = 0.006). Twenty-four amputations (33.3 %) were complicated by wound infection during the initial hospitalization, with wound cultures growing a variety of organisms, most frequently Enterococcus species and Enterobacter cloacae. When subway injuries were separated by AKAs and BKAs, patients with AKAs underwent more irrigation and debridement procedures on average (10.3 vs. 5.8; P = 0.006), had a higher rate of wound infections (58.8 % vs. 25.0 %; P = 0.018), and had longer hospital stays (50.4 vs. 32.2 days; P = 0.047)., Conclusion: Subway-related amputations are associated with longer ICU stays and a history of alcohol use disorder compared to non-subway traumatic amputations. Approximately 1/3 of these patients are expected to develop a wound infection, with Enterococcus and Enterobacter species being the most commonly identified organisms. Further research into high-energy, traumatic amputations, including subway injuries, may help improve prognostication of patient outcomes, identify potential in-hospital complications, and proactively direct differences in care compared to the standard for non-subway-related amputations., Level of Evidence: Prognostic Level III., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paid consultant – Stryker Medical Biologics – PL, corresponding author Other Professional Activities – Novadip - PL, corresponding author. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Treatment of ankle and pilon fractures in the setting of diabetes mellitus (DM) is challenging due to a propensity for postoperative complications. Limb salvage is a primary concern following these injuries, as below knee amputation (BKA) occurs at an unacceptably high rate. Primary retrograde tibiotalocalcaneal (TTC) joint nailing without articular preparation has emerged as a solution to treat diabetics with ankle and pilon fractures to mitigate surgical complications and prevent BKA. The technique minimizes surgical dissection and has previously demonstrated utility in fragility fracture, however, there are few studies regarding the use of this technique in the setting of DM., Methods: A retrospective review of diabetic patients treated with retrograde TTC nailing without articular preparation was conducted over a seven-year period. Patients were included in the study if they were skeletally mature, diabetic, and treated with retrograde TTC nailing without articular preparation over a minimum follow up period of eight months. Treatment with other forms of fixation and pediatric or adolescents were excluded. A cohort of 25 patients met the inclusion criteria. Data was collected on demographics, injury characteristics, and surgical outcomes. The average follow up period was 2.45 years (IQR 986)., Results: The averages for age, BMI, and Hemoglobin A1c (HbA1c) of the cohort were 64.6 (IQR 9.6), 36.7 (IQR 11.5), and 7.6 % (IQR 1.4), respectively. A majority of fractures were a closed supination-external rotation mechanism resulting from a fall from standing. The average LOS was 9.1 days (IQR 8). An ambulatory level was maintained in 72 % of patients. Limb salvage was achieved for 84 % of the cohort. Four patients ultimately required BKA. HbA1c and fracture-related infection (FRI) were statistically significant risk factors associated with BKA. For every 1 % increase in HbA1c, there was 2.63-fold odds of developing BKA. The surgical complication and reoperation rate were 56 %., Conclusion: Although limb salvage was achieved for most patients within the cohort, high rates of postoperative complications and reoperations were observed using this technique. Prospective comparative studies are needed to further validate the use of retrograde nailing without articular preparation in the setting of DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Objective: Metabolic bone disease (MBD, referring to osteopenia and osteoporosis) and its sequelae are associated with substantial morbidity, mortality, and healthcare costs. MBD screening and bone densitometry referral are underutilized in the general population despite published screening guidelines. Prior studies have correlated vertebral body Hounsfield unit (HU) measurements with MBD. The purpose of this study is to use this method to identify the prevalence of undiagnosed MBD in patients presenting to the hospital after high energy trauma, and to determine whether opportunistic MBD screening using this method would be valuable in this cohort., Design: Retrospective review., Setting: Level 1 trauma center and safety net hospital., Patients: 307 patients with a high energy femur fracture who underwent abdomen/pelvis computed tomography (CT) were identified from a trauma database., Intervention: L1 vertebral body radio density (in Hounsfield units, HU) was measured from trauma CT scans. Risk factors for MBD were identified from the medical record., Main Outcome Measurements: Prevalence of MBD and proportion of patients with MBD risk factors meriting further work-up., Results: The prevalence of MBD among high energy trauma patients was similar to the age-matched general population. Over half (50.5 %) of all patients had at least one risk factor for MBD. Among patients 50 to 64 years of age with any given MBD risk factor, over a third of individuals had MBD. In this population, the prevalence of MBD was highest (40.0 %) among those who used tobacco products and had a concurrent alcohol use disorder., Conclusion: Opportunistic screening for MBD using a CT measurement technique can facilitate earlier diagnosis and treatment for affected individuals presenting after high energy trauma. Opportunistic screening may be particularly impactful in pre-menopausal women and in men, who frequently have MBD risk factors but who have a low referral rate for bone density testing and treatment., Level of Evidence: Diagnostic level III., Competing Interests: Declaration of competing interest None., (Copyright © 2025. Published by Elsevier Ltd.)

Purpose: To describe experiences of adolescents taking continuous drospirenone (DRSP-C) oral contraceptives, without placebo, for menstrual suppression, including breakthrough bleeding and other side-effects., Methods: This was a retrospective chart review of adolescents prescribed DRSP-C for menstrual suppression. Demographics and indications for DRSP-C were collected on the visit where DRSP-C was prescribed. Data through the final follow-up visit during the study period included documented effects and side-effects of DRSP-C and continuation of therapy. Statistical analyses were primarily descriptive., Results: Patients prescribed DRSP-C were included (n = 136). Dysmenorrhea was the most common indication for DRSP-C (58.8%, n = 80/136) followed by endometriosis (44.8%, n = 61/136). The median time on DRSP-C for the 116 patients who were able to initiate treatment was 12.3 months (interquartile range [IQR] 6.8, 17.4). Patients trialed, on average, 2 other forms of menstrual management before starting DRSP-C (IQR 1, 3). Pelvic pain or dysmenorrhea resolution or improvement was reported in 84.6% (44/52) of dysmenorrhea patients, and 77.8% (28/36) of pelvic pain patients. Almost half of patients reported breakthrough bleeding on DRSP-C (41.3%, n = 48/116); however, only 11 patients (42%, 11/26) discontinued DRSP-C because of it. Within the study period, 22.4% (n = 26/116) of patients discontinued DRSP-C, with a median treatment duration of 101 days (IQR 71, 157). Among patients who discontinued DRSP-C, the most common reason was breakthrough bleeding (42%, n = 11/26)., Discussion: DRSP-C for menstrual suppression was well tolerated in adolescents, with most patients reporting resolution or improvement of their indication for taking DRSP-C. Findings demonstrate DRSP-C is a viable option for menstrual suppression in adolescents., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: With crewed deep space exploration on the horizon, preparation for potential astronaut health crises in space missions has become vital. Administration of anaesthesia and analgesia presents many challenges owing to constraints specific to space (physiologic and ergonomic challenges associated with microgravity) and nonspecific factors (isolation and lack of supplies). Regional anaesthesia can be the safest option; however, we hypothesised that the ergonomics of microgravity would compromise ease and accuracy of nerve blocks., Methods: We evaluated the feasibility of regional anaesthesia in a simulated microgravity environment (free-floating underwater conditions) using a meat (bovine muscle) model. Forty meat models were randomised for injection under simulated microgravity or normal gravity conditions. Success rates were determined by blinded assessors after injection. Parameters assessed included time to block, ease of image acquisition, and ease of needle placement., Results: The median time to block in normal gravity was 27 (interquartile range 21-69) s vs 35 (interquartile range 22-48) s in simulated microgravity (P=0.751). Ease of image acquisition was similar in both conditions, as was ease of needle placement. There was no significant difference in the rate of accidental intraneural injections (5% vs 5%), with block success rates comparable in both scenarios (80% normal gravity vs 85% microgravity, P>0.999)., Conclusions: Regional anaesthesia appears feasible for experts in simulated microgravity despite the ergonomic challenges. Although our model has limitations and might not fully capture the complexities of actual space conditions, it provides a foundation for future research into anaesthesia and analgesia during deep space missions., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Paper-based patient records have been associated with disorganization and redundancy and thus lack of efficiency and security. The electronic health record (EHR) is an electronic record for patient health information that has alleviated many of the traditional issues associated with paper-based records. However, in the current era of the internet and with the variability of EHR systems, privacy, security, and interoperability remain challenges of the current patient health information management systems. Blockchain technologies provide an opportunity to address many of the challenges associated with current EHR systems. In addition, new frameworks have explored the utility of blockchain-based applications in addressing concerns in different medical disciplines such as neurosurgery. This review discusses these applications, including blockchain-based solutions impacting all of medicine, relating to the EHR, and directly relating to neurosurgery. This review also discusses blockchain technology and the related intricacies for appreciating the relevant frameworks, while also highlighting the challenges associated with this technology., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Research productivity is on the rise as neurosurgical residency positions become increasingly competitive. We explored the relationship between neurosurgical residency applicant's senior author's research productivity and matching into a neurosurgery residency program., Methods: A retrospective analysis of bibliometric data for applicants who matched into neurosurgery in 2022-2023 and their senior authors was conducted using Scopus., Results: Logistic regression revealed a significant association between h-index values and top 40 match outcomes (P = 0.038). The maximum h-index of senior authors significantly predicted matches at top 40 programs (P = 0.003). Affiliation with a top 40 medical school increased both applicant and senior author h-indices (P = 0.05, P < 0.001 respectively). Linear regression of the maximum h-index of senior authors in preresidency publications explained 42% of this variability (P < 0.001). A multiple linear regression model incorporating this with publication number elucidated 69% of the variance in interns' h-index. Authorship data categorized as first, second, and third author positions showed 1847 first author, 1417 second author, and 118 third author publications over 2-years. Applicants at top 40 residency programs had more first and second author publications compared to those from nontop 40 programs (P = 0.0158, P = 0.0275)., Conclusions: There is a strong correlation between a neurosurgical applicant's academic output and that of their senior authors. The number of publications and the maximum h-index of senior authors significantly predict applicant h-indices. We also demonstrated that there is a significant difference in the academic productivity of applicants and senior authors of applicants who successfully match into a top 40 i(h)5 rated neurosurgical residency., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) is an established and expanding therapy for treatment-refractory obsessive-compulsive disorder. Previous work has suggested that a white matter circuit providing hyperdirect input from the dorsal cingulate and ventrolateral prefrontal regions to the subthalamic nucleus could be an effective neuromodulatory target., Methods: We tested this concept by attempting to retrospectively explain through predictive modeling the ranks of clinical improvement as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 10 patients with obsessive-compulsive disorder who underwent DBS to the ventral anterior limb of internal capsule with subsequent programming uninformed by the putative target tract., Results: Rank predictions were carried out using the tract model by a team that was completely uninvolved in DBS planning and programming. Predicted Y-BOCS improvement ranks significantly correlated with actual Y-BOCS improvement ranks at the 6-month follow-up (r = 0.75, p = .013). Predicted score improvements correlated with actual Y-BOCS score improvements (r = 0.72, p = .018)., Conclusions: Here, we provide data in a first-of-its-kind report suggesting that normative tractography-based modeling can blindly predict treatment response in DBS for obsessive-compulsive disorder., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: In the UK, smoking prevalence in people with depression (34%) and anxiety (29%) is more than double that of the general population (13%). People who stop smoking improve their mental health with comparable effect sizes found for antidepressants. In England, online psychological therapy is a standard treatment for depression and anxiety. Online therapy is an acceptable setting for smoking cessation support; however, integrated smoking and mental health support is not available. This novel study aims to assess the acceptability and feasibility of an online smoking cessation intervention, and trial procedures, offered alongside online mental health treatment as it offers increased reach to people with common mental health difficulties who smoke., Methods: A two-armed; Intervention (Integrated SilverCloud smoking cessation support) and control group (SilverCloud usual care), pragmatic, randomised controlled feasibility trial. We aim to recruit 500 adult smokers eligible for online mental health treatment. Follow-up will be conducted at 3-months and 6-months. We will assess the acceptability and feasibility of the trial procedures (i.e., recruitment, data completeness, self-reported acceptability and satisfaction) and the intervention (i.e., self-reported quit attempt, engagement with the smoking cessation and mental health programs, smoking cessation medicine and e-cigarette use, self-reported acceptability and satisfaction) and pilot clinical outcomes (i.e., biologically validated smoking abstinence, anxiety, depression, quality of health)., Conclusion: If the Trial is successful, a randomised controlled effectiveness trial will follow to examine whether integrated smoking cessation and mental health treatment increases smoking abstinence and improves depression and anxiety compared to usual care., Trial Registration: ISRCTN10612149 (https://doi.org/10.1186/ISRCTN10612149), 02/02/2023., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DD, GH, DR, and DH are employees of Amwell, a telehealth company that owns the Silvercloud product., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Junctional ectopic tachycardia (JET) complicates congenital heart surgery in 2% to 8.3% of cases. JET is associated with postoperative morbidity in single-center studies. We used the Pediatric Cardiac Critical Care Consortium data registry to provide a multicenter epidemiologic description of treated JET., Methods: This is a retrospective study (February 2019-August 2022) of patients with treated JET. Inclusion criteria were (1) <12 months old at the index operation, and (2) treated for JET <72 hours after surgery. Diagnosis was defined by receiving treatment (pacing, cooling, and medications). A multilevel logistic regression analysis with hospital random effect identified JET risk factors. Impact of JET on outcomes was estimated by margins/attributable risk analysis using previous risk-adjustment models., Results: Among 24,073 patients from 63 centers, 1436 (6.0%) were treated for JET with significant center variability (0% to 17.9%). Median time to onset was 3.4 hours, with 34% present on admission. Median duration was 2 days (interquartile range, 1-4 days). Tetralogy of Fallot, atrioventricular canal, and ventricular septal defect repair represented >50% of JET. Patient characteristics independently associated with JET included neonatal age, Asian race, cardiopulmonary bypass time, open sternum, and early postoperative inotropic agents. JET was associated with increased risk-adjusted durations of mechanical ventilation (incidence rate ratio, 1.6; 95% CI, 1.5-1.7) and intensive care unit length of stay (incidence rate ratio, 1.3; 95% CI, 1.2-1.3), but not mortality., Conclusions: JET is treated in 6% of patients with substantial center variability. JET contributes to increased use of postoperative resources. High center variability warrants further study to identify potential modifiable factors that could serve as targets for improvement efforts to ameliorate deleterious outcomes., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Inferior phrenic artery to pulmonary artery fistulae are a rare anomaly seen on CT thorax angiogram when evaluating for certain pulmonary pathological conditions. A 79-year-old man with hemothorax on chest X-ray was evaluated by interventional radiology for embolization of a bleeding vessel. During the procedure, a fistulous connection between the right inferior phrenic artery and right pulmonary artery with signs of extravasation was found and embolized, significantly reducing the size of the hemothorax. This case demonstrates that inferior phrenic artery to pulmonary artery fistulae, a rarely seen vascular anomaly, can result in life-threatening hemothorax., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The precise control of complex quantum mechanical systems can unlock applications ranging from quantum simulation to quantum computation. Controlling strongly interacting many-body systems often relies on Floquet Hamiltonian engineering that is achieved by fast switching between Hamiltonian primitives via external control. For example, in our solid-state NMR system, we perform quantum simulation by modulating the natural Hamiltonian with control pulses. As the Floquet heating errors scale with the interpulse delay, δt, it is favorable to keep δt as short as possible, forcing our control pulses to be short duration and high power. Additionally, high-power pulses help to minimize undesirable evolution from occurring during the duration of the pulse. However, such pulses introduce an appreciable phase-transient control error, a form of unitary error. In this work, we detail our ability to diagnose the error, calibrate its magnitude, and correct it for π/2-pulses of arbitrary phase. We demonstrate the improvements gained by correcting for the phase transient error, using a method which we call the "frame-change technique", in a variety of experimental settings of interest. Given that the correction mechanism adds no real control overhead, we recommend that any resonance probe be checked for these phase transient control errors, and correct them using the frame-change technique., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew Stasiuk reports financial support was provided by National Science Foundation. Andrew Stasiuk reports financial support was provided by Laboratory for Physical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lesbian, gay, bisexual, transgender, queer, intersex, and asexual/aromantic (LGBTQIA+) providers improve health outcomes of sexual and gender minority (SGM) patients, which demonstrates the importance of understanding the state of LGBTQIA+ representation at all levels of medical training. The U.S. does not systematically collect sexual orientation and gender identity (SOGI) data from applicants, trainees, and attending physicians, prompting us to wonder whether SGM representation in surgical fields, such as otolaryngology, is adequate. Personal statements submitted to an otolaryngology program from 2019 to 2021 were searched for LGBTQIA+ terms, and those containing LGBTQIA+ terms underwent full text review to determine whether applicants identified themselves as LGBTQIA+. Across these 2 application cycles, the sampled residency program received 928 applications. Only 2 applicants of 928 (0.2%) self-disclosed their LGBTQIA+ identities in their personal statements. These results signify a scarcity of SGM diversity in otolaryngology and warrant deeper exploration into factors preventing residency applicants from self-disclosure of LGBTQIA+ identities., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Pneumoperitoneum is a common complication after penetrating abdominal trauma, gastric ulcer, or colitis in which free air is present in the peritoneal or retroperitoneal space. Sole pneumoretroperitoneum, which refers to gas in the retroperitoneal space, is a rare entity, and when significant, results in a characteristic radiographic sign known as "Dirty Mass." Common causes include penetrating trauma or perforation of the retroperitoneal portions of the gastrointestinal tract (duodenum, ascending colon, descending colon, and rectum). Our case describes a 59-year-old female admitted for sudden onset RLQ abdominal pain with Dirty Mass sign on abdominal KUB. Early recognition of these key radiographic findings accelerates management and reduces the risk of developing complications., (© 2024 The Authors.)

Molecular imprinting has advanced towards synthesizing whole-cell imprints of microorganisms such as bacteria on various sensor surfaces including wire electrodes, quartz crystal microbalances, and microparticles (MPs). We recently introduced cell-imprinted polymers (CIPs) coated on MPs, called CIP-MPs, for bacteria recovery from water. In this paper, we have advanced towards rapid fluorometric Escherichia coli (E. coli) detection by applying fluorescent magnetic CIP-MPs, which were captured by soft ferromagnetic microstructures integrated into a microfluidic channel. The shape of ferromagnetic microstructures was optimized numerically to enhance the magnetophoretic accumulation of CIP-MPs in the microchannel. The device was then fabricated and the flow rate required to enhance bacteria capturing efficiency by CIP-MPs was determined. Decreasing the flow rate reduced the flow-induced drag and increased the interactions between the bacteria and imprinted CIP cavities. Fluorescent imaging of the accumulated CIP-MPs was done before and after bacteria capturing to quantify the changes in the fluorescence intensity as E. coli cells were captured by CIP-MPs in the microchannel. The dose-response curve of the sensor at 0-10 9  CFU/mL bacterial counts was obtained. Using the 3- and 10-sigma methods on the dose-response curve, the limits of detection (LOD) and quantification (LOQ) of the sensor were determined to be 4 × 10 2 and 3 × 10 3  CFU/mL, respectively, within a dynamic range of 10 2 -10 7  CFU/mL. Lastly, the specificity of the CIP-MPbased sensor towards E. coli was tested and confirmed using Sarcina as a non-specific target bacterium. In summary, our developed sensor offers a promising approach for rapid and low-cost detection of bacteria in water and is suitable for development of portable and durable all-polymeric sensors for point-of-need detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events., Methods: We searched Ovid MEDLINE, Embase, Cochrane Central, and Scopus databases for studies comparing commonly used non-neuraxial analgesic techniques for midline laparotomy in adult patients. The co-primary outcomes of the study were 24-h cumulative opioid consumption and 24-h resting pain score, reported as i.v. morphine equivalents and 11-point numerical rating scale, respectively. We performed a frequentist meta-analysis using a random-effects model and a cluster-rank analysis of the co-primary outcomes., Results: Of 6115 studies screened, 67 eligible studies were included (n=4410). Interventions with the greatest reduction in 24-h cumulative opioid consumption compared with placebo/no intervention were single-injection quadratus lumborum block (sQLB; mean difference [MD] -16.1 mg, 95% confidence interval [CI] -29.9 to -2.3, very low certainty), continuous transversus abdominis plane block (cTAP; MD -14.0 mg, 95% CI -21.6 to -6.4, low certainty), single-injection transversus abdominis plane block (sTAP; MD -13.7 mg, 95% CI -17.4 to -10.0, low certainty), and continuous rectus sheath block (cRSB; MD -13.2 mg, 95% CI -20.3 to -6.1, low certainty). Interventions with the greatest reduction in 24-h resting pain score were cRSB (MD -1.2, 95% CI -1.8 to -0.6, low certainty), cTAP (MD -1.0, 95% CI -1.7 to -0.2, low certainty), and continuous wound infusion (cWI; MD -0.7, 95% CI -1.1 to -0.4, low certainty). Clustered-rank analysis including the co-primary outcomes showed cRSB and cTAP blocks to be the most efficacious interventions., Conclusions: Based on current evidence, continuous rectus sheath block and continuous transversus abdominis plane block were the most efficacious non-neuraxial techniques at reducing 24-h cumulative opioid consumption and 24-h resting pain scores after midline laparotomy (low certainty). Future studies should compare techniques for upper vs lower midline laparotomy and other non-midline abdominal incisions., Clinical Trial Registration: PROSPERO Registration Number: CRD42021269044., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: Muscle elasticity can be quantified with shear wave elastography (SWE) and has been used as an estimate of muscle force but reliability has not been established for lower leg muscles. The purpose of this study was to examine the intra-rater and inter-rater reliability of elasticity measures in non-weight-bearing (NWB) and weight-bearing (WB) for the tibialis anterior (TA), tibialis posterior (TP), peroneal longus (PL), and peroneal brevis (PB) muscles using SWE., Methods: A total of 109 recreationally active healthy adults participated. The study employed a single-cohort, same-day repeated-measures test-retest design. Elasticity, measured in kilopascals as the Young's modulus, was converted to the shear modulus. All four muscles were measured in NWB and at 90% WB., Results: Intra-rater reliability estimates were good to excellent for NWB (ICC = 0.930-0.988) and WB (ICC = 0.877-0.978) measures. Inter-rater reliability estimates were moderate to good (ICC = 0.500-0.795) for NWB measures and poor to good (ICC = 0.346-0.910) for WB measures., Conclusion: Despite the studies poor to good inter-rater variability, the intra-rater reproducibility represents the potential benefit of SWE in NWB and WB. Establishing the reliability of SWE with clinical and biomechanical approaches may aid in improved understanding of the mechanical properties of muscle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study examined the washoff of Bacillus globigii (Bg) spores from concrete, asphalt, and grass surfaces by stormwater. Bg is a nonpathogenic surrogate for Bacillus anthracis, which is a biological select agent. Areas (2.74 m × 7.62 m) of concrete, grass, and asphalt were inoculated twice at the field site during the study. Spore concentrations were measured in runoff water after seven rainfall events (1.2-65.4 mm) and complimentary watershed data were collected for soil moisture, depth of water in collection troughs, and rainfall using custom-built telemetry units. An average surface loading of 10 7.79 Bg spores/m 2 resulted in peak spore concentrations in runoff water of 102, 260, and 4.1 CFU/mL from asphalt, concrete, and grass surfaces, respectively. Spore concentrations in the stormwater runoff were greatly reduced by the third rain event after both inoculations, but still detectable in some samples. When initial rainfall events occurred longer after the initial inoculation, the spore concentrations (both peak and average) in the runoff were diminished. The study also compared rainfall data from 4 tipping bucket rain gauges and a laser disdrometer and found they performed similarly for values of total rainfall accumulation while the laser disdrometer provided additional information (total storm kinetic energy) useful in comparing the seven different rain events. The soil moisture probes are recommended for assistance in predicting when to sample sites with intermittent runoff. Sampling trough level readings were critical to understanding the dilution factor of the storm event and the age of the sample collected. Collectively the spore and watershed data are useful for emergency responders faced with remediation decisions after a biological agent incident as the results provide insight into what equipment to deploy and that spores may persist in runoff water at quantifiable levels for months. The spore measurements are also a novel dataset for stormwater model parameterization for biological contamination of urban watersheds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Recent trends suggest that autism is more common in females than traditionally held. Additionally, some argue that females express autistic traits differently than males. Dimensional views of autism could shed light on these issues, especially with regards to understudied behavioral areas, such as sensory processing. We examined autistic traits, sensory processing, anxiety, and related behaviors in a large sample of neurotypical young adult males and females ( n = 1,122; 556 female; ages 19-26). Participants completed an online survey containing questionnaires related to the above. Between groups statistical analyses, as well as within groups correlations and mediation analyses containing these constructs were then computed. We also carried out a cluster analysis to establish groups with behavioral similarities and estimate within-cluster male/female ratios. Results showed modest differences in the overall expression of autistic traits and sensory processing, if any, between males and females. Conversely, more detailed examination of survey subtests and mediation analyses revealed differing profiles between these groups. Cluster analysis uncovered a group comprised of both males (69.8%) and females (30.2%) who exhibited elevated degrees of autism-related behaviors, suggesting a higher proportion of females than would be predicted by traditional ratios. Taken together, these findings suggest that males and females may not differ as much as previously thought in their general levels of autistic traits or sensory processing, but may present with distinct profiles of such behaviors. These novel results add to our understanding of autistic traits in females and have the potential to positively influence diagnostic and support practices., Competing Interests: Conflict of Interest Statement The authors of the current manuscript report no conflict of interest Declaration of Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The purpose of this study was to examine sex-based trends in incidence of elective abdominal aortic aneurysm (AAA), ruptured AAA, ruptured AAA repair, and AAA-related mortality., Methods: A retrospective analysis of patients presenting with AAA from 2005 to 2015 was conducted. Rates of elective AAA repair, ruptured AAA, ruptured AAA repair, and mortality were obtained from linking provincial administrative data using medical services insurance billing number. The age-adjusted incidence of elective AAA repair, overall rate of ruptured AAA, ruptured AAA repair, and AAA-related mortality was calculated for each sex based on Canadian census estimates, adjusted to the Canadian standard population. Weighted linear regression was performed to analyze trends in incidence over time., Results: One thousand nine hundred eighty-six elective AAA repairs were identified, of which 1,098 were repaired open and 898 underwent endovascular abdominal aneurysm repair (EVAR). Five hundred and seventy ruptured AAAs were identified, of which 295 (52%) were repaired: 259 open and 36 EVAR. The proportion of ruptured AAA that was repaired did not change over time (P = 0.54). The proportion repairs performed using EVAR increased significantly in both elective (P < 0.001) and rupture repairs (P < 0.001). During the study period, 662 patients died of AAA-associated mortality. The average incidence of elective AAA repair in men was 29.3 (95% confidence interval (CI): 27.8 to 30.8) per 100,000 and decreased over time (P = 0.04), whereas the average incidence in women was 9.2 [8.3 to 10.0] and stable (P = 0.07). The incidence of open elective AAA repair was 10.5 [9.9-11.1] with a decreasing trend over time (P < 0.001) and EVAR was 9.0 (8.5-9.6) with an increasing trend over time (P < 0.001). A decreasing trend of overall ruptured AAA (5.4 [5.0-5.9], P < 0.001), ruptured AAA repair (2.9 [2.5-3.2], P = 0.02), and of AAA-related mortality (6.2 [5.8-6.8], P < 0.001) was found, with consistent trends in both sexes. The incidence of open ruptured AAA repair decreased over time (P = 0.001) whereas the incidence of ruptured EVAR remained stable (P = 0.23)., Conclusions: The incidence of elective AAA repair is decreasing in males but not females, whereas the incidence of rupture has decreased in both sexes. This has translated into reduced incidence of AAA-related mortality. Increased adoption of EVAR for ruptured AAA should continue these trends., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: When developing a clinical prediction model, assuming a linear relationship between the continuous predictors and outcome is not recommended. Incorrect specification of the functional form of continuous predictors could reduce predictive accuracy. We examine how continuous predictors are handled in studies developing a clinical prediction model., Methods: We searched PubMed for clinical prediction model studies developing a logistic regression model for a binary outcome, published between July 01, 2020, and July 30, 2020., Results: In total, 118 studies were included in the review (18 studies (15%) assessed the linearity assumption or used methods to handle nonlinearity, and 100 studies (85%) did not). Transformation and splines were commonly used to handle nonlinearity, used in 7 (n = 7/18, 39%) and 6 (n = 6/18, 33%) studies, respectively. Categorization was most often used method to handle continuous predictors (n = 67/118, 56.8%) where most studies used dichotomization (n = 40/67, 60%). Only ten models included nonlinear terms in the final model (n = 10/18, 56%)., Conclusion: Though widely recommended not to categorize continuous predictors or assume a linear relationship between outcome and continuous predictors, most studies categorize continuous predictors, few studies assess the linearity assumption, and even fewer use methodology to account for nonlinearity. Methodological guidance is provided to guide researchers on how to handle continuous predictors when developing a clinical prediction model., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Innovation in sequencing instrumentation is increasing the per-batch data volumes and decreasing the per-base costs. Multiplexed chemistry protocols after the addition of index tags have further contributed to efficient and cost-effective sequencer utilization. With these pooled processing strategies, however, comes an increased risk of sample contamination. Sample contamination poses a risk of missing critical variants in a patient sample or wrongly reporting variants derived from the contaminant, which are particularly relevant issues in oncology specimen testing in which low variant allele frequencies have clinical relevance. Small custom-targeted next-generation sequencing (NGS) panels yield limited variants and pose challenges in delineating true somatic variants versus contamination calls. A number of popular contamination identification tools have the ability to perform well in whole-genome/exome sequencing data; however, in smaller gene panels, there are fewer variant candidates for the tools to perform accurately. To prevent clinical reporting of potentially contaminated samples in small next-generation sequencing panels, we have developed MICon (Microhaplotype Contamination detection), a novel contamination detection model that uses microhaplotype site variant allele frequencies. In a heterogeneous hold-out test cohort of 210 samples, the model displayed state-of-the-art performance with an area under the receiver-operating characteristic curve of 0.995., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 increased uncertainty for most and was especially disruptive to autistic people and their families, due in part to tendencies toward intolerance for uncertainty across this population. As such, COVID presented a natural experiment of uncertainty and its correlates in autism. Previous reports have shown associations between intolerance of uncertainty, sensory difficulty, and stress., Aims: We investigated changes in sensory difficulties and stress associated with COVID-related increases in uncertainty., Methods and Procedures: Primary caregivers of 47 autistic children (ages 6-15) completed online surveys containing questions about demographics, experiences, and supports received during the pandemic. Additionally, caregivers filled out measures of intolerance of uncertainty and sensory processing for both pre- and during-COVID conditions., Outcomes and Results: Eighty nine percent of children had significant sensory difficulties before the pandemic. This group showed significant increases in sensory difficulties and intolerance of uncertainty during the pandemic. These changes were significantly correlated with each other, suggesting that as uncertainty increased so did sensory difficulties. Disruption to routine was also significantly correlated with sensory differences and child, household, and parent stress., Conclusions and Implications: Our findings add to fundamental understanding of the relationship between uncertainty, sensory processing, and stress by leveraging a natural experiment in increased uncertainty. These results have the potential to contribute to improved supports for autistic individuals in clinical, educational, home, and other settings., Competing Interests: Declaration of interest statement: The authors whose names are listed above certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest, in the subject matter or materials discussed in this manuscript.

Background: Skillful communication with attention to patient and care partner priorities can help people with serious illnesses. Few patient-facing agenda-setting tools exist to facilitate such communication., Objective: To develop a tool to facilitate prioritization of patient and care partner concerns during serious illness visits., Patient or Family Involvement: Two family members of seriously ill individuals advised., Methods: We performed a literature review and developed a prototype agenda-setting tool. We modified the tool based on cognitive interviews with patients, families and clinicians. We piloted the tool with patients, care partners and clinicians to gain an initial impression of its perceived value., Results: Interviews with eight patients, eight care partners and seven clinicians, resulted in refinements to the initial tool, including supplementation with visual cues. In the pilot test, seven clinicians used the tool with 11 patients and 12 family members. Qualitatively, patients and care partners reported the guide helped them consider and assert their priorities. Clinicians reported the tool complemented usual practice. Most participants reported no distress, disruption or confusion., Discussion: Patients, care partners and clinicians appreciated centering patient priorities in serious illness visits using the agenda-setting tool. More thorough evaluation is required., Practical Value: The agenda-setting tool may operationalize elements of good serious illness care., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Development of this manuscript was supported, in part, by the T32 Research Fellowship in Geriatric Mental Health Services Research (T32 MH19132; Bruce).Dr. Scalia has nothing to disclose. Ms. Collison has nothing to disclose. Mr. Wilson Milne has nothing to disclose. Dr. MacMartin has nothing to disclose. Dr. Barnato has nothing to disclose. Ms. Butt has nothing to disclose. Dr. Wasp has nothing to disclose. Dr. Saunders reports holding copyright in The Considerate Suite. Dr. Durand reports fees from EBSCO Health and ACCESS Community Health Network and reports holding copyright in The Considerate Suite. Dr. Nelson reports stocks in Quality Data Management, Inc. Dr. Elwyn reports royalties from Oxford University Press and Radcliffe Press, ownership of &think LLC, SHARPNetwork LLC, and fees from ACCESS Community Health Network, Chicago Federally Qualified Medical Centers, EBSCO Health, Bind Insurance, PatientWisdom Inc, abridge AI Inc. He also reports holding copyright in The Considerate Suite., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods., Methods: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete., Findings: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 μg daily to 1000 μg daily (500 μg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 μg once daily to 500 μg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA., Interpretation: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden., Funding: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline., Competing Interests: Declaration of interests DJJ reports grants from AstraZeneca and personal fees from Sanofi Regeneron, AstraZeneca, and GlaxoSmithKline. BDK report personal fees from AstraZeneca and GlaxoSmithKline. GG reports patents to quantify adherence and to predict exacerbations. CH reports fees from Alphabet, granted as part of employment by Google. DMM reports personal fees from AstraZeneca, Teva, GlaxoSmithKline, Sanofi, and Novartis. RBR reports a patent for the use of acoustics to assess inhaler adherence. JFMvB reports institutional grants from Aardex, AstraZeneca, Chiesi, European Commission COST Action 19132 ENABLE, Lung Alliance Netherlands, Novartis, Trudell Medical and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis, Teva, Trudell Medical, and Vertex. LGH was academic lead for the UK MRC Consortium for Stratified Medicine in Severe Asthma—Industrial Pharma partners Amgen, AstraZeneca, Medimmune, Janssen, Novartis, Roche–Genentech, GlaxoSmithKline, and Boehringer Ingelheim; grants or contracts from GlaxoSmithKline, Schering Plough, Synairgen, Novartis and Roche–Genentech MedImmune, Novartis UK, Roche–Genentech and GlaxoSmithKline; and lectures supported by AstraZeneca, Novartis, Roche–Genentech, Sanofi, Circassia, GlaxoSmithKline, Chiesi, and Teva. RWC reports institutional grants from GlaxoSmithKline, Aerogen, and Enterprise Ireland; personal fees from AstraZeneca, Teva, GlaxoSmithKline, PMD solutions, and Novartis; and a patent for the use of acoustics to assess inhaler adherence, to quantify adherence and to predict exacerbations. EM, CM, MCM, BC, IS, VB, PJK, MB, IC, JF, JH, MK, RC, LL, JW, SP, TAM, and AMNK declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: In biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualized risk prediction., Study Design and Setting: We conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 1st January, 2019, and 5th September, 2019. We used existing spin frameworks and described areas of highly suggestive spin practices., Results: We included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons between developed models in their discussion and predominantly used discrimination measures to support their claims (78%). Thirty-five studies (56%) used an overly strong or leading word in their title, abstract, results, discussion, or conclusion., Conclusion: The potential for spin needs to be considered when reading, interpreting, and using studies that developed and validated prognostic models in oncology. Researchers should carefully report their prognostic model research using words that reflect their actual results and strength of evidence., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Research reported in this publication was supported by grants from the National Institutes of Health, National Institute of Mental Health (RF1MH117800-01) and National Institute on Aging (P30AG066518, P30AG008017). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Objective: Ruptured abdominal aortic aneurysms (RAAAs) are surgical emergencies that require immediate and expert treatment. It has been unclear whether presentation during evenings and weekends, when "on call" teams are primarily responsible for patient care, is associated with worse outcomes. Our objective was to evaluate the outcomes of patients presenting with RAAAs after-hours vs during the workday., Methods: A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients who had presented to the hospital with RAAAs during the workday (Monday through Friday, 6 am to 6 pm) were compared with those who had presented after-hours (6 pm to 6 am during the week and on weekends). The baseline and operative characteristics were identified for all patients through the available databases and a review of the medical records. Mortality before surgery, 30-day mortality, and operative mortality were compared between groups using multivariable logistic regression, adjusting for factors clinically significant on univariable analysis., Results: A total of 390 patients with RAAAs were identified from 2005 to 2015, of whom 205 (53%) had presented during the workday and 185 (47%) after-hours. The overall chance of survival (OCS) was 45% overall, 49% if admitted to hospital, and 64% if surgery had been performed. During the workday, the OCS was 43% overall, 48% if admitted to hospital, and 67% if surgery had been performed. After-hours, the OCS was 46% overall, 49% if admitted to hospital, and 61% if surgery had been performed. Mortality before surgery was increased for patients who had presented to the hospital during the workday compared with after-hours (36% vs 26%; P = .04). The 30-day mortality (57% vs 54%; P = .62), rates of operative management (63% vs 72%; P = .06), and operative mortality (33% vs 39%; P = .33) were similar between the workday and after-hours groups (57% vs 54%; P = .06). After adjusting for significant clinical variables, the patients who had presented with RAAAs after-hours had had a similar odds of dying before surgery (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.41-1.03), operative management (OR, 1.47; 95% CI, 0.93-2.31), 30-day mortality (OR, 0.98; 95% CI, 0.63-1.51), and operative mortality (OR, 1.33; 95% CI, 0.78-2.26). In the subgroup of patients presenting to a hospital with endovascular capabilities, patients presenting after-hours had had similar odds of 30-day mortality (OR, 1.07; 95% CI, 0.57-2.02), and operative mortality (OR, 1.14; 95% CI, 0.58-2.23)., Conclusions: We found that patients presenting to the hospital with RAAAs after-hours did not have increased adjusted odds of mortality before surgery, operative management, 30-day mortality, or operative mortality., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Centralization of vascular surgery care for Ruptured Abdominal Aortic Aneurysms (RAAAs) to high-volume tertiary centers may hinder access to timely surgical intervention for patients in remote areas. The objective of this study was to determine the association between distance from vascular care and mortality from RAAAs in the province of Nova Scotia, Canada., Methods: A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients were divided into groups by estimated travel time from their place of residence to the tertiary center (<1 hr and ≥1 hr) using geographic information software. Baseline and operative characteristics were identified for all patients through available databases and completed through chart review. Mortality at home, during transfer to the vascular center, and overall 30-day mortality were compared between groups using t-test and chi-squared test, as appropriate. Multivariable logistic regression analysis was used to calculate the independent effect of travel time on survival outcomes., Results: A total of 567 patients with RAAA were identified from 2005-2015, of which 250 (44%) resided <1 hr travel time to the tertiary center and 317 (56%) resided ≥1 hr. On multivariable analysis, travel time ≥1 hr from vascular care was an independent predictor of mortality at home (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.07-2.63, P = 0.02), mortality prior to operation (OR 2.64, 95% CI 1.81-3.83, P < 0.001), and overall 30-day mortality (OR 1.61, 95% CI 1.10-2.37, P = 0.02). In patients who received an operation (n = 294), there was no association between increased travel time and mortality (OR 1.02, 95% CI 0.60-1.73, P = 0.94)., Conclusions: Travel time ≥1 hr to the tertiary center is associated with significantly higher mortality from ruptured abdominal aortic aneurysm (AAA). However, there was no difference in overall chance of survival between groups for patients that underwent AAA repair. Therefore, strategies to facilitate early detection, and timely transfer to a vascular surgery center may improve outcomes for patients with RAAA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Lynch Syndrome (LS), the most common cause of hereditary colorectal cancer (CRC), is characterised by pathogenic variants in mismatch repair (MMR) genes. Universal testing of all CRCs for LS can increase detection. Rates and outcomes of testing in Ireland's national CRC screening programme have not been examined previously., Methods: CRCs diagnosed at two screening sites between 2015 and 2020 were identified. Patient records were used to determine if CRCs had been tested for MMR deficiency and if detected, what downstream testing to rule out LS or genetic testing to confirm LS was undertaken., Results: Over five years, 206 CRCs were diagnosed. Testing for LS was carried out for 100% of CRCs at site A and 69% of CRCs at site B. Of CRCs tested for LS, 14 (8%) were MMR deficient. After downstream testing for BRAF mutation or hypermethylation of MLH1, three CRCs were identified as potentially LS-related. Of these two individuals declined genetic testing and one was lost to follow-up., Conclusions: By 2020 both sites had implemented universal testing of all CRCs for LS. A small number of individuals were identified as being eligible for genetic testing for LS, however those offered declined testing and one individual was lost to follow up. This highlights the importance of universal testing and the need for referral pathways to ensure all appropriate individuals are referred onwards to genetic services., Competing Interests: Declarations of interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Intramedullary femoral nails are measured intraoperatively using fluoroscopy. This study aims to investigate whether distance from the olecranon to fingertips can be used to estimate nail length preoperatively by evaluating agreement of the two measurements. Such preoperative measurements may provide a likely range of nails needed for theatre and serve as an adjunct to intraoperative measurements., Methods: In 70 patients, long leg radiographs were used to make linear measurements from the piriformis fossa and greater trochanter to the distal physeal scar of the femur. These were compared to measurements from the olecranon to the tip of each digit and Bland-Altman agreement analysis was performed. Train and Trial groups were formed to develop models for estimation and to then test their accuracy., Results: Bland-Altman analysis revealed a fixed bias, indicative of average difference between measurements, of 1.4 cm when comparing the elbow-thumb length to maximum femoral nail length for piriformis fossa entry and 3.5 cm using greater trochanter entry, informing the "rule of thumb". Elbow-thumb length plus 1.4 cm or 3.5 cm predicts nail length to a range of ± one nail increment. The rule can be used to preoperatively predict a range of three nails from which there is a 94-97% likelihood the appropriate intramedullary nail would be selected., Conclusions: The "rule of thumb" may serve as a simple to use tool for preoperative planning and a technical check to assess the "reasonableness" of intraoperative measurements before implantation of the device. It has the potential to reduce operating time and nail wastage., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

The aftermath of extreme flood events can be particularly devastating for residential communities in proximity to flood-prone petrochemical facilities, as they are likely to experience multiple impacts from a single flood event. Hazard impacts could be from flood inundation to their properties, and floodwaters carrying contaminants from nearby facilities into their homes. While property acquisition or buyouts have been effectively used as a flood mitigation strategy, current buyout selection processes only factor in flood exposure, thereby ignoring other hazards such as exposure of properties to potential chemical substance transfer. In this paper, we identify properties that are eligible for flood buyouts but are also at a high risk of contaminant transferal during extreme flood events. We apply a benefit-cost analysis methodology to assess the economic viability of buyouts and proximity metrics to prioritize buyouts of contaminant-prone properties in Galena Park, Texas. Results indicate that, in selected flood-only property acquisition scenarios, cumulative avoided flood losses exceed the cost of property acquisition. However, although with lower cost-benefit values, a selection criterion that factors a combination of flood and contaminant-prone properties as buyouts results in multiple properties being removed from harm's way. Our findings emphasize the potential economic benefits of applying a multi-hazard selection criterion in dealing with flood property buyouts, especially in socially vulnerable communities with high exposure to both flooding and contaminant transfer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: This study was conducted to determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac operation in a contemporary multicenter cohort., Methods: This was an observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac operation. We explored overall percentage fluid overload, postoperative day 1 percentage fluid overload, peak percentage fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome., Results: The cohort included 2223 patients. In-hospital mortality was 3.9% (n = 87). Overall median peak percentage fluid overload was 4.9% (interquartile range, 0.4%-10.5%). Peak percentage fluid overload and postoperative day 1 percentage fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio, 1.11; 95% CI, 1.08-1.14), ICU length of stay (incidence rate ratio, 1.08; 95% CI, 1.03-1.12), and hospital length of stay (incidence rate ratio, 1.09; 95% CI, 1.05-1.13)., Conclusions: Time to first negative daily fluid balance, but not percentage fluid overload, is associated with improved postoperative outcomes in neonates after cardiac operation. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In-office needle arthroscopy (IONA) has been available in various iterations for decades. Studies have described it as comparable if not superior to magnetic resonance imaging for identifying intra-articular pathology with associated cost savings per patient. A new IONA system has been brought to market with a modernized user interface and disposable handpieces offering the opportunity to address intra-articular pathology. This article outlines the use of this IONA system for the postoperative evaluation of an osteochondral allograft transplant.

Background: Gallbladder cancer (GBC) is an aggressive malignancy associated with a high risk of recurrence and mortality. We used a machine-based learning approach to stratify patients into distinct prognostic groups using preperative variables., Methods: Patients undergoing curative-intent resection of GBC were identified using a multi-institutional database. A classification and regression tree (CART) was used to stratify patients relative to overall survival (OS) based on preoperative clinical factors., Results: CART analysis identified tumor size, biliary drainage, carbohydrate antigen 19-9 (CA19-9) levels, and neutrophil-lymphocyte ratio (NLR) as the factors most strongly associated with OS. Machine learning cohorted patients into four prognostic groups: Group 1 (n = 109): NLR ≤1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 2 (n = 88): NLR >1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 3 (n = 46): CA19-9 >20, no drainage, tumor size <5.0 cm; Group 4 (n = 77): tumor size <5.0 cm with drainage OR tumor size ≥5.0 cm. Median OS decreased incrementally with CART group designation (59.5, 27.6, 20.6, and 12.1 months; p < 0.0001)., Conclusions: A machine-based model was able to stratify GBC patients into four distinct prognostic groups based only on preoperative characteristics. Characterizing patient prognosis with machine learning tools may help physicians provide more patient-centered care., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of this Neonatal and Pediatric Heart and Renal Outcomes Network study was to describe the epidemiology and outcomes of cardiac surgery-associated acute kidney injury (CS-AKI) after cardiac surgery without cardiopulmonary bypass (non-CPB)., Methods: We performed a retrospective study of neonates (≤30 days) who underwent non-CPB cardiac surgery at 22 centers affiliated with the Pediatric Cardiac Critical Care Consortium. CS-AKI was defined using the modified Kidney Disease: Improving Global Outcomes serum creatinine and urine output criteria from postoperative days 0 to 6. CS-AKI defined by serum creatinine was further subclassified into transient (resolved by postoperative day 3) and persistent/late (≥3 days). Multivariable regression analyses were used to determine risk factors for CS-AKI and associations with outcomes of ventilation hours and cardiac intensive care unit length of stay., Results: Five hundred eighty-two neonates (median age at surgery, 9 days [interquartile range, 5-15], 25% functional single ventricle] were included. CS-AKI occurred in 38.3%: Rate and severity varied across centers. Aggregate daily CS-AKI prevalence peaked on postoperative day 1 (17.1%). No stage of CS-AKI was associated with ventilation hours or length of stay. Persistent/late CS-AKI occurred in 48 patients (8%). Prostaglandin use and single-ventricle surgery were associated with persistent/late CS-AKI. Higher baseline serum creatinine but not persistent/late CS-AKI was associated with longer ventilation duration and intensive care unit length of stay after adjusting for confounders., Conclusions: Kidney Disease: Improving Global Outcomes-defined CS-AKI occurred commonly in neonates undergoing non-CPB cardiac surgery. However most CS-AKI was transient, and no CS-AKI classification was associated with worse outcomes. Further work is needed to determine the CS-AKI definition that best associates with outcomes in this cohort., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear., Research Question: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?, Study Design and Methods: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated., Results: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm., Interpretation: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04344587; URL: www., Clinicaltrials: gov., (Copyright © 2022 American College of Chest Physicians. All rights reserved.)

Background: Research addressing sexualised use of GHB to date has largely focussed on gay and bisexual men's GHB use in the context of chemsex, this research has highlighted risks and experiences associated with sexual violence. No studies have included people of diverse sexualities and genders and documented reported practices to ensure mutually gratifying and consensual sex in the context of sexualised drug use (SDU)., Methods: Semi-structured interviews were conducted with 31 people from sexuality and gender diverse communities living in Australia who reported three or more occasions of GHB use in the previous 12 months. Participants were asked about their use of GHB for sex, their experiences of GHB sex and their approaches to negotiating sexual boundaries. Data were analysed thematically., Results: Most participants valued the sexual possibilities enabled by disinhibitory components of GHB and were cognisant of respecting other's sexual boundaries in the context of GHB sex. Participants reported strategies to ensure communication prior to and throughout GHB sex. However, several participants narrated experiences of GHB sex that they felt were distressing and, in some circumstances, sexually violent. In most instances participant's resisted terminology of sexual violence or non-consent as descriptors of their experience and none reported accessing sexual violence services., Conclusion: Positive strategies to facilitate sexual communication prior to and throughout GHB sex should be reflected in health promotion and service level responses to promote affirmative and continuous consent among people who use GHB for sex. Education initiatives to help people engaged in SDU to recognise and respond to sexual violence if it occurs ought to be prioritised., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Histone chaperones facilitate the assembly and disassembly of nucleosomes and regulate DNA accessibility for critical cellular processes. Spn1 is an essential, highly conserved histone chaperone that functions in transcription initiation and elongation in a chromatin context. Here we demonstrate that Spn1 binds H3-H4 with low nanomolar affinity, residues 85-99 within the acidic N-terminal region of Spn1 are required for H3-H4 binding, and Spn1 binding to H3-H4 dimers does not impede (H3-H4) 2 tetramer formation. Previous work has shown the central region of Spn1 (residues 141-305) is important for interaction with Spt6, another conserved and essential histone chaperone. We show that the C-terminal region of Spn1 also contributes to Spt6 binding and is critical for Spn1 binding to nucleosomes. We also show Spt6 preferentially binds H3-H4 tetramers and Spt6 competes with nucleosomes for Spn1 binding. Combined with previous results, this indicates the Spn1-Spt6 complex does not bind nucleosomes. In contrast to nucleosome binding, we found that the Spn1-Spt6 complex can bind H3-H4 dimers and tetramers and H2A-H2B to form ternary complexes. These important results provide new information about the functions of Spn1, Spt6, and the Spn1-Spt6 complex, two essential and highly conserved histone chaperones., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: GHB is used among some sexuality and gender diverse populations at elevated rates, however little qualitative research has explored GHB use among these populations with regards to diverse contexts, settings, practices, and experiences of use. Internationally, harms relating to GHB overdose appear to be increasing. Research outlining consumers' experiences of GHB-related pleasures and their strategies to reduce harms may inform GHB education and intervention responses., Methods: N = 31 participants reporting three or more occasions of GHB use within the previous 12 months were recruited via digital advertising and snowball methods. Semi-structured interviews were conducted, data were transcribed and analysed in NVivo using a thematic framework analysis. Emergent themes were charted, and divergences and convergences were considered with regards to the sexuality and gender identities of participants., Results: Pleasures associated with GHB were described in relation to the sensation of the GHB high and experiences of intimacy, and connection. GHB was used to enhance socialising and sex in domestic, private, and commercial venues. Participants prioritised terminology of 'control' when describing their practices associated with GHB dosing, measuring, timing and peer moderation. Most participants reported personal experience of GHB overdose with loss of consciousness., Conclusion: Participants' near-ubiquitous experience of GHB overdose highlights ongoing education needs around overdose prevention. Efforts must target people new to GHB use who appeared particularly susceptible to overdose. Inconsistencies in understandings around GHB overdose, the perceived severity of overdose and the differences between GHB and its precursors GBL and 1,4-BD, highlight potential focus areas of future education responses. Further research is required to better understand consumers' experiences of sexual violence in the context of GHB use., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)