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Abstract Background Early detection of melanoma, a potentially lethal type of skin cancer with high prevalence worldwide, improves patient prognosis. In retrospective studies, artificial intelligence (AI) has proven to be helpful for enhancing melanoma detection. However, there are few prospective studies confirming these promising results. Existing studies are limited by low sample sizes, too homogenous datasets, or lack of inclusion of rare melanoma subtypes, preventing a fair and thorough evaluation of AI and its generalizability, a crucial aspect for its application in the clinical setting. Methods Therefore, we assessed “All Data are Ext” (ADAE), an established open-source ensemble algorithm for detecting melanomas, by comparing its diagnostic accuracy to that of dermatologists on a prospectively collected, external, heterogeneous test set comprising eight distinct hospitals, four different camera setups, rare melanoma subtypes, and special anatomical sites. We advanced the algorithm with real test-time augmentation (R-TTA, i.e., providing real photographs of lesions taken from multiple angles and averaging the predictions), and evaluated its generalization capabilities. Results Overall, the AI shows higher balanced accuracy than dermatologists (0.798, 95% confidence interval (CI) 0.779–0.814 vs. 0.781, 95% CI 0.760–0.802; p = 4.0e−145), obtaining a higher sensitivity (0.921, 95% CI 0.900–0.942 vs. 0.734, 95% CI 0.701–0.770; p = 3.3e−165) at the cost of a lower specificity (0.673, 95% CI 0.641–0.702 vs. 0.828, 95% CI 0.804–0.852; p = 3.3e−165). Conclusion As the algorithm exhibits a significant performance advantage on our heterogeneous dataset exclusively comprising melanoma-suspicious lesions, AI may offer the potential to support dermatologists, particularly in diagnosing challenging cases.

Abstract Background High sedentary times (ST) is highly prevalent in patients with coronary artery disease (CAD), highlighting the need for behavioural change interventions that effectively reduce ST. We examined the immediate and medium-term effect of the SIT LESS intervention on changes in ST among CAD patients enrolled in cardiac rehabilitation (CR). Methods CAD patients participating in CR at 2 regional hospitals were included in this randomized controlled trial (1:1, stratified for gender and hospital). The control group received CR, whereas SIT LESS participants additionally received a 12-week hybrid behaviour change intervention. The primary outcome was the change in accelerometer-derived ST from pre-CR to post-CR and 3 months post-CR. Secondary outcomes included changes in ST and physical activity characteristics, subjective outcomes, and cardiovascular risk factors. A baseline constrained linear mixed-model was used. Results Participants (23% female; SIT LESS: n = 108, control: n = 104) were 63 ± 10 years. Greater ST reductions were found for SIT LESS compared to control post-CR (-1.7 (95% confidence interval (CI): -2.0; -1.4) versus − 1.1 (95% CI: -1.4; -0.8) h/day, pinteraction=0.009), but not at 3 months post-CR (pinteraction=0.61). Besides, larger light-intensity physical activity (LIPA) increases were found for SIT LESS compared to control post-CR (+ 1.4 (95% CI: +1.2; +1.6) versus + 1.0 (95% CI: +0.8; +1.3) h/day, pinteraction=0.020). Changes in other secondary outcomes did not differ among groups. Conclusion SIT LESS transiently reduced ST and increased LIPA, but group differences were no longer significant 3 months post-CR. These findings highlight the challenge to induce sustainable behaviour changes in CAD patients without any continued support. Trial registration Netherlands Trial Register: NL9263. Registration Date: 24 February 2021.

Abstract We explore long-lived particle (LLP) searches using non-pointing photons at the LHC as a probe for sterile-to-sterile and active-to-sterile transition magnetic dipole moments of sterile neutrinos. We consider heavy sterile neutrinos with masses ranging from a few GeV to several hundreds of GeV. We discuss transition magnetic dipole moments using the Standard Model effective field theory and low-energy effective field theory extended by sterile neutrinos (N R SMEFT and N R LEFT) and also provide a simplified UV-complete model example. LLP searches at the LHC using non-pointing photons will probe sterile-to-sterile dipole moments two orders of magnitude below the current best constraints from LEP, while an unprecedented sensitivity to sterile neutrino mass of about 700 GeV is expected for active-to-sterile dipole moments. For the UV model example with one-loop transition magnetic moments, the searches for charged lepton flavour violating processes in synergy with LLP searches at the LHC can probe new physics at several TeV mass scales and provide valuable insights into the lepton flavour structure of new physics couplings.

Abstract Background The Ross procedure is a technically complex operation to address the pathology of the aortic valve. Prior attempts at widespread implementation have been plagued with variations in effectiveness. We report our initial programmatic outcomes using dissemination and implementation (D&I) science frameworks, with an aim to define both programmatic efficacy and effectiveness. The study design was a single center, explanatory sequential mixed methods evaluation of a Ross surgery program from June 2020 to April 2023. Quantitative measures for baseline patient characteristics and postoperative outcomes were summarized. Qualitative measures were obtained using semi-structured interviews and characterized using implementation science frameworks. Results A total of 71 patients underwent the Ross procedure at a single academic center. Mean age was 40 years (± 13). There were no perioperative deaths or valve-related reinterventions (0%). During the follow-up period, 2 (2.8%) patients required re-operation and 2 (2.8%) required balloon dilation of the pulmonary homograft. Qualitative measures noted communication and prospective self-audit facilitated measures of effectiveness, as dichotomy within expected vs. observed outcomes led to program modifications. Collaboration across hospital systems promoted adoption and implementation, which led to the incorporation of the Ross procedure into accepted organizational practice. Conclusions In this formative evaluation, limited-efficacy outcomes demonstrated similar programmatic success to data from other established centers. With the prerequisite center volume and case selection, the Ross procedure is a safe and efficacious treatment for aortic valvular disease. Implementation science can be used both in real-time and retrospectively to guide organizational efforts to improve outcomes and to improve the translation of results across centers.

Abstract Attaining complete anomeric control is still one of the biggest challenges in carbohydrate chemistry. Glycosyl cations such as oxocarbenium and dioxanium ions are key intermediates of glycosylation reactions. Characterizing these highly-reactive intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Although C-2 acyl neighbouring-group participation has been well-studied, the reactive intermediates in more remote participation remain elusive and are challenging to study. Herein, we report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors. First, we use a combination of quantum-chemical calculations and infrared ion spectroscopy to determine the structure of the cationic glycosylation intermediate in the gas-phase. In addition, we establish the structure and exchange kinetics of highly-reactive, low-abundance species in the solution-phase using chemical exchange saturation transfer, exchange spectroscopy, correlation spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple-bond correlation nuclear magnetic resonance spectroscopy. Finally, we apply C-3 acyl neighbouring-group participation to the synthesis of complex bacterial oligosaccharides. This combined approach of finding answers to fundamental physical-chemical questions and their application in organic synthesis provides a robust basis for elucidating highly-reactive intermediates in glycosylation reactions.

Abstract Fluorescent molecule-based direct labeling of amplified DNA is a sensitive method employed across diverse DNA detection and diagnostics systems. However, using pre-labeled primers only allows for the attachment of a single fluorophore to each DNA strand and any modifications of the system are less flexible, requiring new sets of primers. As an alternative, direct labeling of amplified products with modified nucleotides is available, but still poorly characterized. To address these limitations, we sought a direct and adaptable approach to label amplicons produced through Loop-mediated isothermal amplification (LAMP), using labeled nucleotides (dUTPs) rather than primers. The focus of this study was the development and examination of a direct labeling technique of specific genes, including those associated with drug resistance in Mycobacterium tuberculosis. We used 5-(3-Aminoallyl)-2′-deoxyuridine-5′triphosphate, tagged with 5/6-TAMRA (TAMRA-dUTP) for labeling LAMP amplicons during the amplification process and characterized amplification and incorporation efficiency. The optimal TAMRA-dUTP concentration was first determined based on amplification efficiency (0.5% to total dNTPs). Higher concentrations of modified nucleotides reduced or completely inhibited the amplification yield. Target size also showed to be determinant to the success of amplification, as longer sequences showed lower amplification rates, thus less TAMRA incorporated amplicons. Finally, we were able to successfully amplify all four M. tuberculosis target genes using LAMP and TAMRA-modified dUTPs.

Aims: Proper preoperative planning benefits fracture reduction, fixation, and stability in tibial plateau fracture surgery. We developed and clinically implemented a novel workflow for 3D surgical planning including patient-specific drilling guides in tibial plateau fracture surgery. Methods: A prospective feasibility study was performed in which consecutive tibial plateau fracture patients were treated with 3D surgical planning, including patient-specific drilling guides applied to standard off-the-shelf plates. A postoperative CT scan was obtained to assess whether the screw directions, screw lengths, and plate position were performed according the preoperative planning. Quality of the fracture reduction was assessed by measuring residual intra-articular incongruence (maximum gap and step-off) and compared to a historical matched control group. Results: A total of 15 patients were treated with 3D surgical planning in which 83 screws were placed by using drilling guides. The median deviation of the achieved screw trajectory from the planned trajectory was 3.4° (interquartile range (IQR) 2.5 to 5.4) and the difference in entry points (i.e. plate position) was 3.0 mm (IQR 2.0 to 5.5) compared to the 3D preoperative planning. The length of 72 screws (86.7%) were according to the planning. Compared to the historical cohort, 3D-guided surgery showed an improved surgical reduction in terms of median gap (3.1 vs 4.7 mm; p = 0.126) and step-off (2.9 vs 4.0 mm; p = 0.026). Conclusion: The use of 3D surgical planning including drilling guides was feasible, and facilitated accurate screw directions, screw lengths, and plate positioning. Moreover, the personalized approach improved fracture reduction as compared to a historical cohort. Cite this article: Bone Jt Open 2024;5(1):46–52.

Objective:. To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background:. mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods:. This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results:. Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%–30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%–20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%–21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4–1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3–1.1). Conclusion:. Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

Abstract Background Abdominal aortic endoleaks after endovascular aneurysm repair might be position-dependent, therefore undetectable using supine imaging. We aimed to determine the feasibility and benefit of using a low-field tiltable magnetic resonance imaging (MRI) scanner allowing to study patients who can be imaged in both supine and upright positions of endoleaks. Methods Ten EVAR patients suspected of endoleak based on ultrasound examination were prospectively included. MRI in upright and supine positions was compared with routine supine computed tomography angiography (CTA). Analysis was performed through (1) subjective image quality assessment by three observers, (2) landmark registration between MRI and CTA scans, (3) Euclidean distances between renal and endograft landmarks, and (4) evaluation of endoleak detection on MRI by a consensus panel. Statistical analysis was performed by one-way repeated measures analysis of variance. Results The image quality of upright/supine MRI was inferior compared to CTA. Median differences in both renal and endograft landmarks were approximately 6–7 mm between upright and supine MRI and 5–6 mm between supine MRI and CTA. In the proximal sealing zone of the endograft, no differences were found among all three scan types (p = 0.264). Endoleak detection showed agreement between MRI and CTA in 50% of the cases, with potential added value in only one patient. Conclusions The benefit of low-field upright MRI for endoleak detection was limited. While MRI assessment was non-inferior to standard CTA in detecting endoleaks in selected cases, improved hardware and sequences are needed to explore the potential of upright MRI in patients with endoleaks. Relevance statement Upright low-field MRI has limited clinical value in detecting position-dependent endoleaks; improvements are required to fulfil its potential as a complementary modality in this clinical setting. Key points • Upright MRI shows potential for imaging endoleaks in aortic aneurysm patients in different positions. • The image quality of upright MRI is inferior to current techniques. • Upright MRI complements CTA, but lacks accurate deformation measurements for clinical use. • Advancements in hardware and imaging sequences are needed to fully utilise upright MRI capabilities. Graphical Abstract

BackgroundDistal radius fractures are the most frequently encountered fractures in Western societies, typically affecting patients aged 50 years and older. Although this is a common injury, the best treatment for these fractures in older patients is still under debate. ObjectiveThis prospective study aims to compare the outcome of operatively and nonoperatively treated distal radius fractures in the older population. Only patients with distal radius fractures for which equipoise regarding the optimal treatment exists will be included. MethodsThis prospective international multicenter observational cohort study will be designed as a natural experiment. Natural experiments are observational studies in which treatment allocation is determined by factors outside the control of the investigators but also (largely) independent of patient characteristics. Patients aged 65 years and older with an acute distal radius fracture will be considered for inclusion. Treatment allocation (operative vs nonoperative) will be based on the local preferences of the treating hospital either in Switzerland or the Netherlands. Hence, the process governing treatment allocation resembles that of randomization. Patients will be identified after treatment has been initiated. Based on the radiographs and baseline information of the patient, an expert panel of 6 certified trauma surgeons from 2 regions will provide their treatment recommendation. Only patients for whom the experts disagree on treatment recommendations will ultimately be included in the study (ie, for whom there is a clinical equipoise). For these patients, both operative and nonoperative treatment of distal radius fractures are viable, and treatment choice is predominantly determined by personal or local preference. The primary outcome will be the Patient-Rated Wrist Evaluation score at 12 weeks. Secondary outcomes will include the Physical Activity Score for the Elderly, the EQ questionnaire, pain, the living situation, range of motion, complications, and radiological outcomes. By including outcomes such as living situation and the Physical Activity Score for the Elderly, which are not relevant for younger cohorts, valuable information to tailor treatment to the needs of the older population can be gained. According to the sample size collection, which was based on the minimal important clinical difference of the Patient-Rated Wrist Evaluation, 92 patients will have to be included, with at least 46 patients in each treatment group. ResultsEnrollment began in July 2023 and is expected to continue until summer 2024. The final follow-up will be 2 years after the last patient is included. ConclusionsAlthough many trials on this topic have previously been published, there remains an ongoing debate regarding the optimal treatment for distal radius fractures in older patients. This observational study, which will use a fairly new methodological study design, will provide further information on treatment outcomes for older patients with distal radius fractures for which to date equipoise exists regarding the optimal treatment. International Registered Report Identifier (IRRID)DERR1-10.2196/52917

Ringed seals are consumed in Greenland and are therefore included as a key biomonitoring species with the focus on pollution exposure and health effects. Ringed seals in Central West Greenland (Qeqertarsuaq) and in North West Greenland (Qaanaaq) were analyzed for metal concentrations in the liver and histological changes in the liver and kidney. The mean liver concentration of mercury in Qaanaaq was 3.73 ± 5.01 µg/g ww (range: 0.28–23.29 µg/g ww), and the mean cadmium concentration was 7.80 ± 8.95 µg/g ww (range: 0.013–38.79 µg/g ww). For Qeqertarsuaq, the liver concentration of mercury was 1.78 ± 1.70 µg/g ww (range: 0.45–8.00 µg/g ww) and the mean cadmium concentration was 11.58 ± 6.32 µg/g ww (range: 0.11–25.45 µg/g ww). Age had a positive effect on the liver concentrations of metals, while no effect was found for sex or histological changes. The prevalence of histological changes in liver tissue decreased in the following order: random pattern mononuclear cell infiltration (92.1%), portal cell infiltration (68.4%), hepatic intracellular fat (18.4%), portal fibrosis (7.9%), focal hepatic fibrosis (7.9%), bile duct hyperplasia/fibrosis (7.9%) and lipid granuloma (2.6%). For kidney tissue, the prevalence of histological changes decreased in the following order: glomerular mesangial deposits (54.1%) > glomerular basement membrane thickening (45.9%) > THD (40%) > tubular hyaline casts (14.0%) > glomerular atrophy (13.5%) > dilated tubules (13.5%) > glomerular hyper-cellularity (10.8%) > mononuclear cell infiltrations (8.1%).

Introduction Rotational malalignment occurs in up to 30% of cases after intramedullary nailing of tibial shaft fractures. The aim of this study is to assess the clinical feasibility of a newly introduced standardised intraoperative fluoroscopy protocol coined ‘C-arm rotational view (CARV)’ in order to reduce the risk of rotational malalignment during intramedullary nailing of tibial shaft fractures. The CARV includes predefined fluoroscopy landmark views of the uninjured side to obtain correct alignment of the injured side with use of the rotation of the C-arm.Methods and analysis This randomised controlled trial will be conducted in a level 1 trauma centre. Adult patients with an open or closed tibial fracture, eligible for intramedullary nailing, will be enrolled in the study. The interventional group will undergo intramedullary nailing guided by the CARV protocol to obtain accurate alignment. The control group is treated according to current clinical practice, in which alignment control of the tibia is based on clinical estimation of the treating surgeon. The primary endpoint is defined as the degree of rotation measured on low-dose postoperative CT scans.Ethics and dissemination The study protocol will be performed in line with local ethical guidelines and the Declaration of Helsinki. The results of this trial will be disseminated in a peer-reviewed manuscript. Future patients are likely to benefit from this trial as it aims to provide a clinically feasible and easy-to-use standardised fluoroscopy protocol to reduce the risk for rotational malalignment during intramedullary nailing of tibial shaft fractures.Trial registration number NCT05459038.

Aims: To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials. Methods: This study included 2,388 patients from the HEALTH and FAITH trials, with 90-day and one-year mortality proportions of 3.0% (71/2,388) and 6.4% (153/2,388), respectively. The mean age was 75.9 years (SD 10.8) and 65.9% of patients (1,574/2,388) were female. The algorithms included patient and injury characteristics. Six algorithms were developed, internally validated and evaluated across discrimination (c-statistic; discriminative ability between those with risk of mortality and those without), calibration (observed outcome compared to the predicted probability), and the Brier score (composite of discrimination and calibration). Results: The developed algorithms distinguished between patients at high and low risk for 90-day and one-year mortality. The penalized logistic regression algorithm had the best performance metrics for both 90-day (c-statistic 0.80, calibration slope 0.95, calibration intercept -0.06, and Brier score 0.039) and one-year (c-statistic 0.76, calibration slope 0.86, calibration intercept -0.20, and Brier score 0.074) mortality prediction in the hold-out set. Conclusion: Using high-quality data, the ML-based prediction models accurately predicted 90-day and one-year mortality in patients aged 50 years or older with a FNF. The final models must be externally validated to assess generalizability to other populations, and prospectively evaluated in the process of shared decision-making. Cite this article: Bone Jt Open 2023;4(3):168–181.

Abstract Tritium beta-decay is the most promising approach to measure the absolute masses of active light neutrinos in the laboratory and in a model-independent fashion. The development of Cyclotron Radiation Emission Spectroscopy techniques and the use of atomic tritium has the potential to improve the current limits by an order of magnitude in future experiments. In this paper, we analyse the potential sensitivity of such future searches to keV-mass sterile neutrinos and exotic interactions of either the active or sterile neutrinos. We calculate the relevant decay distributions in both energy and angle of the emitted electron with respect to a potential polarisation of the tritium, including the interference with the Standard Model case as well as incorporating relevant final state corrections for atomic tritium. We present projected sensitivities on the active-sterile neutrino mixing and effective coupling constants of exotic currents, demonstrating the potential to probe New Physics in tritium experiments.

Abstract A large experimental program is being mounted to search for neutrinoless double-beta decay over the next decade. Multiple experiments using different target isotopes are being prepared to explore the whole parameter space allowed for inverted-ordered light neutrinos, and have the potential to make discoveries in several other scenarios, including normal-ordered light neutrinos and other exotic mechanisms. We investigate to what extent long-range and exotic short-range contributions may be distinguished by combining measurements of the decay half-life across isotopes in the framework of a global Bayesian analysis. We demonstrate how measurements in two isotopes will constrain the parameter space up to a two-fold degeneracy, and how a further measurement in a third isotope removes such a degeneracy. We also discuss the impact of uncertainties and correlations in nuclear matrix element calculations. Our work motivates an experimental program measuring neutrinoless double-beta decay in more than one isotope, as this would break parameter degeneracies and advance our understanding of particle physics beyond the Standard Model.

A versatile cytosine base editor system is developed to achieve highly efficient C to T conversion in the genome of a series of phytopathogenic bacteria, including Xanthomonas, Pseudomonas, Erwinia, and Agrobacterium.

This study investigates patterns of communication among non-coresident kin in the aftermath of the COVID-19 pandemic using data from the New York City Robin Hood Poverty Tracker. Over half of New Yorkers spoke to their non-coresident family members several times a week during the pandemic, and nearly half increased their communication with non-coresident kin since March 2020. Siblings and extended kin proved to be especially important ties activated during the pandemic. New Yorkers were most likely to report increased communication with siblings. A quarter of respondents reported that they increased communication with at least one aunt, uncle, cousin, or other extended family member. Although non-Hispanic White respondents reported the highest frequency of communication with kin, it was those groups most impacted by COVID-19—foreign-born, Black, and Hispanic New Yorkers—who were most likely to report that they increased communication with kin in the wake of the pandemic.

Abstract Background Prolonged sitting is associated with increased risk of obesity, type 2 diabetes and cardiovascular disease. Occupational sitting accounts for up to 50 h/week for employees. This pilot study assessed the acceptability of stair climbing as an interruption to sitting throughout working hours, and provided preliminary data of the effects on glucose and lipid profiles. Methods A quasi-experimental design was conducted involving 16 sedentary office workers (five females and 11 males) for intervention (n = 8) and control groups (n = 8) with mean age of 36.38 (5.58). For the eight-week intervention, a continuous four-floor stair climb and descent was performed eight times/day spread evenly over the working day. A prompt to climb was presented on the participant’s computer eight times/day. Participants in the experimental group recorded daily floors climbed and steps (measured using pedometers) in a weekly log sheet. Blood samples were collected pre and post intervention to test effects on fasting glucose and 2 h plasma glucose, triglycerides, and total (TC), LDL and HDL cholesterol. Experimental participants were interviewed at the end of the study. The Wilcoxon signed rank test was used to compare the median changes (pre-post) of the dependent variables. Results On average, the experimental group climbed 121 floors/week when prompted. There were significant reductions in fasting blood glucose, TC and LDL, as well as the derived measures of ‘bad’ cholesterol and the TC/HDL ratio in the experimental group. Post-experimental interviews indicated that the interruption to sitting was well tolerated. Conclusion Prompted stair climbing activity had impacts on health outcomes and was found acceptable to employees at work. Trial registration Ethics for this study was approved by Science, Technology, Engineering and Mathematics Ethical Review Committee, University of Birmingham with ethics reference number ERN_15_0491.

Abstract We investigate the pair-production of Right-Handed Neutrinos (RHNs) via a $$B-L$$ B - L $$Z'$$ Z ′ boson and present the sensitivity studies of the active-sterile neutrino mixing ( $$|V_{\mu N}|$$ | V μ N | ) at the High-Luminosity run of the LHC (HL-LHC) and a future pp collider (FCC-hh). We focus on RHN states with a mass of $$10-70$$ 10 - 70 GeV which naturally results in displaced vertices for small $$|V_{\mu N}|$$ | V μ N | . Being produced through a mass resonance with $$M_{Z'} \ge 1$$ M Z ′ ≥ 1 TeV, the RHNs are heavily boosted, leading to collimated decay products that give rise to fat-jets. We investigate the detection prospect of dedicated signatures in the inner detector and the muon spectrometer, namely a pair of displaced fat-jets and the associated tracks, respectively. We find that both the HL-LHC and FCC-hh can be sensitive to $$|V_{\mu N}| > 10^{-6}$$ | V μ N | > 10 - 6 and $$|V_{\mu N}| > 10^{-7}$$ | V μ N | > 10 - 7 with the number of events reaching $${\mathcal {O}}(10)$$ O ( 10 ) and $${\mathcal {O}}(10^3)$$ O ( 10 3 ) , respectively. This allows probing the generation of light neutrino masses through the Seesaw mechanism.

This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing.

A murine muskelin knockout induces increased exploratory drive and alters cognition and functional connectivity. These effects correlate with actin-dependent changes in dendritic branching, spine structure, and AMPAR-mediated synaptic transmission.

Abstract The red‐footed booby (Sula sula) is one of the most common pantropical seabird species, but its populations have been declining in the Caribbean region and elsewhere. We used distance sampling from point‐counts to estimate population size of red‐footed boobies in Mona Island, Puerto Rico, USA, before and during the breeding season in 2019. We compared results from early morning and early night surveys to determine the best survey time given that many individuals are foraging at sea during the daylight hours but not at night. We also examined the suitability of drone photography to survey active nests (a measure of breeding pairs) and compared it to point count and transect survey data. Point count surveys show that an estimated 6,130 birds occupied the colony, which is more than double previous estimates for Mona Island. Our results also showed that to avoid underestimates, red‐footed booby colonies are best surveyed at night as they yield higher bird densities than daytime surveys. For the same reason, daytime photographic surveys with a drone underestimated population size compared to nighttime point‐count surveys. However, drones were more effective than ground surveys in detecting active nests, and thus breeding pairs, which provides a better estimate of the resident population of a colony. We recommend that nighttime surveys are tailored to site‐specific conditions to improve estimates of red‐footed boobies, while drones can save significant effort and time in monitoring numbers of active nests in the remote and rugged islands where red‐footed boobies typically nest.

IntroductionMost studies about rib fractures focus on mortality and morbidity. Literature is scarce on long term and quality of life (QoL) outcomes. Therefore, we report QoL and long-term outcomes after rib fixation in flail chest patients.MethodsA prospective cohort study of clinical flail chest patients admitted to six level 1 trauma centres in the Netherlands and Switzerland between January 2018 and March 2021. Outcomes included in-hospital outcomes and long-term outcomes, such as QoL measurements 12 months after hospitalization using the EuroQoL five dimensions (EQ-5D) questionnaire.ResultsSixty-one operatively treated flail chest patients were included. Median hospital length of stay was 15 days and intensive care length of stay was 8 days. Sixteen (26%) patients developed pneumonia and two (3%) died. One year after hospitalization the mean EQ5D score was 0.78. Complication rates were low and included hemothorax (6%) pleural effusion (5%) and two revisions of the implant (3%). Implant related irritation was commonly reported by patients (n = 15, 25%).ConclusionsRib fixation for flail chest injuries can be considered a safe procedure and with low mortality rates. Future studies should focus on quality of life rather than solely short-term outcomes.Trial registration: Registered in the Netherlands Trial Register NTR6833 on 13/11/2017 and the Swiss Ethics Committees Registration Number 2019-00668

The rodent visual system has attracted great interest in recent years due to its experimental tractability, but the fundamental mechanisms used by the mouse to represent the visual world remain unclear. In the primate, researchers have argued from both behavioral and neural evidence that a key step in visual representation is ‘figure-ground segmentation’, the delineation of figures as distinct from backgrounds. To determine if mice also show behavioral and neural signatures of figure-ground segmentation, we trained mice on a figure-ground segmentation task where figures were defined by gratings and naturalistic textures moving counterphase to the background. Unlike primates, mice were severely limited in their ability to segment figure from ground using the opponent motion cue, with segmentation behavior strongly dependent on the specific carrier pattern. Remarkably, when mice were forced to localize naturalistic patterns defined by opponent motion, they adopted a strategy of brute force memorization of texture patterns. In contrast, primates, including humans, macaques, and mouse lemurs, could readily segment figures independent of carrier pattern using the opponent motion cue. Consistent with mouse behavior, neural responses to the same stimuli recorded in mouse visual areas V1, RL, and LM also did not support texture-invariant segmentation of figures using opponent motion. Modeling revealed that the texture dependence of both the mouse’s behavior and neural responses could be explained by a feedforward neural network lacking explicit segmentation capabilities. These findings reveal a fundamental limitation in the ability of mice to segment visual objects compared to primates.

Abstract We perform a study of neutrinoless double beta (0νββ) decay mediated by the lightest neutralino of arbitrary mass in the minimal supersymmetric Standard Model (MSSM) under the presence of R-parity violating trilinear interactions. In this scenario, the exchange of the lightest neutralino can result in 0νββ decay of either long-range or short-range behaviour, depending on the neutralino mass. Using nuclear matrix elements calculated in the interacting boson model, we use an interpolation between the long- and short-range behaviours with an approximate formula. The non-observation of 0νββ decay is then used to place constraints on the supersymmetry parameter space, compatible with constraints from collider experiments. We compare these constraints to bounds from pion decays, CKM unitarity and big bang nucleosynthesis.

Understanding the interacting role of climate and habitat in shaping wildlife population dynamics can help to reveal synergistic pathways that drive population resilience or decline across variable and changing environments. Moose (Alces alces) is a pan-boreal herbivore experiencing population declines across large portions of North America; however, the species has shown variable response to climate across its distribution. We investigated moose demographic response to climate and evaluated the interacting role of habitat across 36 years and along a biogeographic gradient in Ontario, Canada that has experienced decadal changes to climate and habitat quality. Moose density exhibited a nonlinear trend that initially increased and then decreased over the study timeframe and was negatively affected by regional and local patterns of winter severity and later frost onset. Recruitment exhibited a monotonic decline and was positively affected by spring heat and deciduous forest cover, while also exhibiting density-dependent effects. The negative response of moose density to winter severity was reduced in Wildlife Management Units (WMUs) with higher proportions of dense canopy cover, supporting expectations that this habitat type improves moose winter mobility and predator avoidance. The negative effect of later frost onset was greater in WMUs with more regenerating forest, and both variables are associated with higher exposure to parasites and predators. Further, density-dependent effects on recruitment were suppressed by warmer springs that support vegetation productivity and in WMUs with higher proportions of dense canopy cover that can provide concealment from predators. Our study illustrates the important role habitat conditions can have to mitigate, or exacerbate, climate-change effects for a wide-spread herbivore occupying variable environments by potentially altering pathways relevant to energetic balance, predation, and parasite transmission. In this system, moose occupying sparse or regenerating forests are more susceptible to adverse climatic effects and should be managed accordingly.

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.

Background: The World Health Organization (WHO) has made recommendations for breastfeeding. These recommendations are to promote proper breastfeeding practices, which are essential for improved child health and survival. Objectives: The study intended to determine the level of awareness of WHO breastfeeding recommendations among nursing mothers in Enugu and how awareness translates into practice. Materials and Methods: A questionnaire was used to assess the awareness of WHO recommendations on breastfeeding and breastfeeding practices of mothers in Enugu, Nigeria. Results: Most (254; 64.1%) mothers have not heard about the WHO recommendation on breastfeeding; majority (81.1%) were aware of exclusive breastfeeding. Antenatal clinics are the commonest source of information on breastfeeding. Only 2.5% mothers intend to breastfeed for the duration recommended. Awareness of WHO recommendations was not associated with decision to breastfeed or frequency of breastfeeding. Younger mothers were less likely to be aware of the recommendation (P = 0.007, OR = 0.559, 95% CI = 0.366–0.851), while antenatal care attendance was associated with increased awareness (P = 0.002, OR = 10.389, 95% CI = 2.439–44.262). Maternal education affected breastfeeding frequency only. Conclusion: Significant gaps exist in awareness of the WHO recommendations on breastfeeding among mothers in Enugu, Nigeria.

Abstract Background A procedure for sentinel lymph node biopsy (SLNB) using superparamagnetic iron-oxide (SPIO) nanoparticles and intraoperative sentinel lymph node (SLN) detection was developed to overcome drawbacks associated with the current standard-of-care SLNB. However, residual SPIO nanoparticles can result in void artefacts at follow-up magnetic resonance imaging (MRI) scans. We present a grading protocol to quantitatively assess the severity of these artefacts and offer an option to minimise the impact of SPIO nanoparticles on diagnostic imaging. Methods Follow-up mammography and MRI of two patient groups after a magnetic SLNB were included in the study. They received a 2-mL subareolar dose of SPIO (high-dose, HD) or a 0.1-mL intratumoural dose of SPIO (low-dose, LD). Follow-up mammography and MRI after magnetic SLNB were acquired within 4 years after breast conserving surgery (BCS). Two radiologists with over 10-year experience in breast imaging assessed the images and analysed the void artefacts and their impact on diagnostic follow-up. Results A total of 19 patients were included (HD, n = 13; LD, n = 6). In the HD group, 9/13 patients displayed an artefact on T1-weighted images up to 3.6 years after the procedure, while no impact of the SPIO remnants was observed in the LD group. Conclusions SLNB using a 2-mL subareolar dose of magnetic tracer in patients undergoing BCS resulted in residual artefacts in the breast in the majority of patients, which may hamper follow-up MRI. This can be avoided by using a 0.1-mL intratumoural dose.

Background: Conventional measures of fracture displacement have low interobserver reliability. This study introduced a novel 3D method to measure tibial plateau fracture displacement and its impact on functional outcome. Methods: A multicentre study was conducted on patients who had tibial plateau fracture surgery between 2003 and 2018. Eligible patients had a preoperative CT scan (slice thickness ≤ 1 mm) and received a Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. A total of 362 patients responded (57%), and assessment of initial and residual fracture displacement was performed via measurement using the 3D gap area (mm2). Patients were divided into four groups based on the 3D gap area size. Differences in functional outcome between these groups were assessed using analysis of variance (ANOVA). Multiple linear regression was used to determine the association between fracture displacement and patient-reported outcome. Results: Functional outcome appeared significantly worse when initial or residual fracture displacement increased. Multivariate linear regression showed that initial 3D gap area (per 100 mm2) was significantly negatively associated with all KOOS subscales: symptoms (−0.9, p < 0.001), pain (−0.0, p < 0.001), ADL (−0.8, p = 0.002), sport (−1.4, p < 0.001), and QoL (−1.1, p < 0.001). In addition, residual gap area was significantly negatively associated with the subscales symptoms (−2.2, p = 0.011), ADL (−2.2, p = 0.014), sport (−2.6, p = 0.033), and QoL (−2.4, p = 0.023). Conclusion: A novel 3D measurement method was applied to quantify initial and residual displacement. This is the first study which can reliably classify the degree of displacement and indicates that increasing displacement results in poorer patient-reported functional outcomes.

Aims: The number of convolutional neural networks (CNN) available for fracture detection and classification is rapidly increasing. External validation of a CNN on a temporally separate (separated by time) or geographically separate (separated by location) dataset is crucial to assess generalizability of the CNN before application to clinical practice in other institutions. We aimed to answer the following questions: are current CNNs for fracture recognition externally valid?; which methods are applied for external validation (EV)?; and, what are reported performances of the EV sets compared to the internal validation (IV) sets of these CNNs? Methods: The PubMed and Embase databases were systematically searched from January 2010 to October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The type of EV, characteristics of the external dataset, and diagnostic performance characteristics on the IV and EV datasets were collected and compared. Quality assessment was conducted using a seven-item checklist based on a modified Methodologic Index for NOn-Randomized Studies instrument (MINORS). Results: Out of 1,349 studies, 36 reported development of a CNN for fracture detection and/or classification. Of these, only four (11%) reported a form of EV. One study used temporal EV, one conducted both temporal and geographical EV, and two used geographical EV. When comparing the CNN’s performance on the IV set versus the EV set, the following were found: AUCs of 0.967 (IV) versus 0.975 (EV), 0.976 (IV) versus 0.985 to 0.992 (EV), 0.93 to 0.96 (IV) versus 0.80 to 0.89 (EV), and F1-scores of 0.856 to 0.863 (IV) versus 0.757 to 0.840 (EV). Conclusion: The number of externally validated CNNs in orthopaedic trauma for fracture recognition is still scarce. This greatly limits the potential for transfer of these CNNs from the developing institute to another hospital to achieve similar diagnostic performance. We recommend the use of geographical EV and statements such as the Consolidated Standards of Reporting Trials–Artificial Intelligence (CONSORT-AI), the Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence (SPIRIT-AI) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis–Machine Learning (TRIPOD-ML) to critically appraise performance of CNNs and improve methodological rigor, quality of future models, and facilitate eventual implementation in clinical practice.

Background and purpose — Artificial intelligence (AI), deep learning (DL), and machine learning (ML) have become common research fields in orthopedics and medicine in general. Engineers perform much of the work. While they gear the results towards healthcare professionals, the difference in competencies and goals creates challenges for collaboration and knowledge exchange. We aim to provide clinicians with a context and understanding of AI research by facilitating communication between creators, researchers, clinicians, and readers of medical AI and ML research. Methods and results — We present the common tasks, considerations, and pitfalls (both methodological and ethical) that clinicians will encounter in AI research. We discuss the following topics: labeling, missing data, training, testing, and overfitting. Common performance and outcome measures for various AI and ML tasks are presented, including accuracy, precision, recall, F1 score, Dice score, the area under the curve, and ROC curves. We also discuss ethical considerations in terms of privacy, fairness, autonomy, safety, responsibility, and liability regarding data collecting or sharing. Interpretation — We have developed guidelines for reporting medical AI research to clinicians in the run-up to a broader consensus process. The proposed guidelines consist of a Clinical Artificial Intelligence Research (CAIR) checklist and specific performance metrics guidelines to present and evaluate research using AI components. Researchers, engineers, clinicians, and other stakeholders can use these proposal guidelines and the CAIR checklist to read, present, and evaluate AI research geared towards a healthcare setting.

Anthropogenic climate change is causing changes to the Arctic sea-ice system with implications for the magnitude and timing of Arctic pelagic and ice-associated (sympagic) primary production that influences food web interactions. Ringed seals (Pusa hispida) are generalist predators that, as a species experience vastly different icescapes from low to high-Arctic latitudes. Quantifying spatial variation in their diet can help us understand how changes in sea-ice dynamics affect trophic interactions in Arctic marine food webs. However, multiple complementary analytical tools to examine variation in carbon source use and trophic dynamics in the diet of ringed seals have not yet been applied across their latitudinal range in the Arctic. We conducted stable isotope analysis (δ13C and δ15N) and measured highly branched isoprenoid diatom lipid biomarkers of ringed seals from the low, intermediate, and high Arctic (from 61.1°N to 77.5°N) to investigate spatial variation in their carbon source use and trophic position in relation to sea-ice dynamics. Both δ13C and highly branched isoprenoids indicated that ringed seals from higher latitudes had more sympagic carbon in their diet (liver δ13C: −18.3 ± 0.2 ‰, HBI: 89.9 ± 2.08 %) than ringed seals at lower latitudes (liver δ13C: −21.1 ± 0.1 ‰, HBI: 22.0 ± 2.73 %). Ringed seal trophic position increased from the low (3.78 ± 0.02) to high (4.76 ± 0.03) Arctic, suggesting increased fish consumption or a different trophic structure coinciding with the latitudinal change in carbon source. Ringed seals demonstrated a clear shift from low to high Arctic in the relative contribution of phytoplanktonic vs sympagic primary production. These patterns are likely linked to the vastly different icescapes in these environments and demonstrate that shifts in primary producer composition and Arctic food webs can be identified in ringed seal diets. Information on these prey and energy shifts over large spatial scales also provides insights into potential future changes to Arctic ecosystem function with continued sea-ice decline.

PurposeFracture-related infection (FRI) is an important complication related to orthopaedic trauma. Although the scientific interest with respect to the diagnosis and treatment of FRI is increasing, data on the microbiological epidemiology remains limited. Therefore, the primary aim of this study was to evaluate the microbiological epidemiology related to FRI, including the association with clinical symptoms and antimicrobial susceptibility data. The secondary aim was to analyze whether there was a relationship between the time to onset of infection and the microbiological etiology of FRI.MethodsFRI patients treated at the University Hospitals of Leuven, Belgium, between January 1st 2015 and November 24th 2019 were evaluated retrospectively. The microbiological etiology and antimicrobial susceptibility data were analyzed. Patients were classified as having an early ( 10 weeks) FRI.ResultsOne hundred ninety-one patients with 194 FRIs, most frequently involving the tibia (23.7%) and femur (18.6%), were included. Staphylococcus aureus was the most frequently isolated pathogen, regardless of time to onset (n=61; 31.4%), followed by S. epidermidis (n=50; 25.8%) and non-epidermidis coagulase-negative staphylococci (n=35; 18.0%). Polymicrobial infections (n=49; 25.3%), mainly involving Gram negative bacilli (GNB) (n=32; 65.3%), were less common than monomicrobial infections (n=138; 71.1%). Virulent pathogens in monomicrobial FRIs were more likely to cause pus or purulent discharge (n=45;54.9%; p=0.002) and fistulas (n=21;25.6%; p=0.030). Susceptibility to piperacillin/tazobactam for GNB was 75.9%. Vancomycin covered 100% of Gram positive cocci.ConclusionThis study revealed that in early FRIs, polymicrobial infections and infections including Enterobacterales and enterococcal species were more frequent. A time-based FRI classification is not meaningful to estimate the microbiological epidemiology and cannot be used to guide empiric antibiotic therapy. Large multicenter prospective studies are necessary to gain more insight into the added value of (broad) empirical antibiotic therapy.

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid inducer line in Arabidopsis thaliana allows for the rapid development of large populations of segregating haploid offspring. Because Arabidopsis haploids can be self-fertilised to give rise to homozygous doubled haploids, the same genotypes can be phenotyped at both the haploid and diploid ploidy level. Here, we compared the phenotypes of recombinant haploid and diploid offspring derived from a cross between two late flowering accessions to map genotype × ploidy (G × P) interactions. Ploidy-specific quantitative trait loci (QTLs) were detected at both ploidy levels. This implies that mapping power will increase when phenotypic measurements of monoploids are included in QTL analyses. A multi-trait analysis further revealed pleiotropic effects for a number of the ploidy-specific QTLs as well as opposite effects at different ploidy levels for general QTLs. Taken together, we provide evidence of genetic variation between different Arabidopsis accessions being causal for dissimilarities in phenotypic responses to altered ploidy levels, revealing a G × P effect. Additionally, by investigating a population derived from late flowering accessions, we revealed a major vernalisation-specific QTL for variation in flowering time, countering the historical bias of research in early flowering accessions.

Knowledge about anatomical shape variations in the pelvis is mandatory for selection, fitting, positioning, and fixation in pelvic surgery. The current knowledge on pelvic shape variation mostly relies on point-to-point measurements on 2D X-ray images and computed tomography (CT) slices. Three-dimensional region-specific assessments of pelvic morphology are scarce. Our aim was to develop a statistical shape model of the hemipelvis to assess anatomical shape variations in the hemipelvis. CT scans of 200 patients (100 male and 100 female) were used to obtain segmentations. An iterative closest point algorithm was performed to register these 3D segmentations, so a principal component analysis (PCA) could be performed, and a statistical shape model (SSM) of the hemipelvis was developed. The first 15 principal components (PCs) described 90% of the total shape variation, and the reconstruction ability of this SSM resulted in a root mean square error of 1.58 (95% CI: 1.53–1.63) mm. In summary, an SSM of the hemipelvis was developed, which describes the shape variations in a Caucasian population and is able to reconstruct an aberrant hemipelvis. Principal component analyses demonstrated that, in a general population, anatomical shape variations were mostly related to differences in the size of the pelvis (e.g., PC1 describes 68% of the total shape variation, which is attributed to size). Differences between the male and female pelvis were most pronounced in the iliac wing and pubic rami regions. These regions are often subject to injuries. Future clinical applications of our newly developed SSM may be relevant for SSM-based semi-automatic virtual reconstruction of a fractured hemipelvis as part of preoperative planning. Lastly, for companies, using our SSM might be interesting in order to assess which sizes of pelvic implants should be produced to provide proper-fitting implants for most of the population.

Displacement of the anterior and posterior column complicates decision making for both-column acetabular fractures. We questioned whether pelvic surgeons agree on treatment strategy, and whether the use of virtual 3D reconstructions changes the treatment strategy of choice. A nationwide cross-sectional survey was performed in all pelvic trauma centers in the Netherlands. Twenty surgeons assessed 15 both-column fractures in 2D as well as 3D. Based on conventional imaging, surgical treatment was recommended in 89% of cases, and by adding 3D reconstructions this was 93% (p = 0.09). Surgical approach was recommended as anterior (65%), posterior (8%) or combined (27%) (poor level of agreement, κ = 0.05) based on conventional imaging. The approach changed in 37% (p = 0.006), with most changes between a combined and anterior approach (still poor level of agreement, κ = 0.13) by adding 3D reconstructions. Additionally, surgeons’ level of confidence increased from good in 38% to good in 50% of cases. In conclusion, surgeons do not agree on the treatment strategy for both-column acetabular fractures. Additional information given by 3D reconstructions may change the chosen surgical approach and increase surgeons’ confidence about their treatment decision. Therefore, virtual 3D reconstructions are helpful for assessing both-column fracture patterns and aid in the choice of treatment strategy.

We examine a macroscopic system in a quantum superposition of two spatially separated localized states as a detector for a stream of weakly interacting relativistic particles. We do this using the explicit example of neutrinos with MeV-scale energy scattering from a solid object via neutral-current neutrino-nucleus scattering. Presuming the (anti)neutrino source to be a nuclear fission reactor, we utilize the estimated flux and coherent elastic neutrino-nucleus cross section to constrain the spatial separation Δx and describe the temporal evolution of the sensing system. Particularly, we find that a potentially measurable relative phase between quantum superposed components is obtained for a single gram scale mass placed in a superposition of spatial components separated by 10^{−14} m under sufficient cooling and background suppression.

Abstract Background The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and other elite lines. The lack of a genome assembly of A188 limits its use as a model for functional studies. Results Here, we present a chromosome-level genome assembly of A188 using long reads and optical maps. Comparison of A188 with B73 using both whole-genome alignments and read depths from sequencing reads identify approximately 1.1 Gb of syntenic sequences as well as extensive structural variation, including a 1.8-Mb duplication containing the Gametophyte factor1 locus for unilateral cross-incompatibility, and six inversions of 0.7 Mb or greater. Increased copy number of carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression in seeds together with low expression of yellow endosperm 1 (y1) reduces carotenoid accumulation, accounting for the white seed phenotype of A188. Furthermore, transcriptome and epigenome analyses reveal enhanced expression of defense pathways and altered DNA methylation patterns of the embryonic callus. Conclusions The A188 genome assembly provides a high-resolution sequence for a complex genome species and a foundational resource for analyses of genome variation and gene function in maize. The genome, in comparison to B73, contains extensive intra-species structural variations and other genetic differences. Expression and network analyses identify discrete profiles for embryonic callus and other tissues.

Abstract Background Stair climbing can be a vigorous lifestyle physical activity, and is associated with healthier lipoprotein profiles, lower body weight and blood pressure, as well as higher aerobic fitness. The present analysis of data from a cohort of late middle-aged men and women examined the association between daily stair climbing and the metabolic syndrome. Methods Data from 782 (423 women) participants (mean (SD) age 58.3 (0.95) years in the Dutch Famine Birth Cohort Study (2002–2004) were used to examine the cross-sectional association between self-reported daily stair climbing and the metabolic syndrome. Stair climbing was assessed by the question ‘Do you climb stairs daily?’ and the metabolic syndrome was defined using the established five components relating to lipid fractions, blood glucose levels, blood pressure and abdominal obesity. Results Not climbing stairs daily was associated with an increased incidence of the metabolic syndrome (OR = 1.90, 95% CI = 1.23, 2.92, p = 0.004) and a greater number of its components (F1,780 = 8.48, p = 0.004): these associations were still evident after adjusting for a variety of potential confounders. Conclusions The most likely explanation for the current findings is that daily stair climbing may be protective against the metabolic syndrome. This result reinforces public health recommendations for increased stair climbing with evidence from physiological outcomes.

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MRI) to determine colonic gas volumes throughout the menstrual cycle. To avoid dietary influence, the participants were instructed to avoid gas-producing foods before their scheduled MRI. We verified the measurement repeatability across the reviewers and obtained an intraclass correlation coefficient of 0.92. There were no significant differences in intraluminal gas volume between menses and non-menses scans (p = 0.679). Even among the women with dysmenorrhea, there was no significant difference in the intraluminal gas volume between menses and non-menses (p = 0.753). During menstruation, the participants with dysmenorrhea had less intraluminal gas than participants without dysmenorrhea (p = 0.044). However, the correlation between the bowel gas volume and the pain symptoms were not significant (p > 0.05). Although increased bowel symptoms and bloating are reported in the women with dysmenorrhea during menses, our results do not support the hypothesis that increased intraluminal gas is a contributing factor. Although dietary treatment has been shown in other studies to improve menstrual pain, the mechanism responsible for abdominal symptoms requires further investigation. Our findings demonstrate that the intraluminal bowel gas volume measurements are feasible and are unaffected by menses under a controlled diet. The method described might prove helpful in future mechanistic studies in clarifying the role of intraluminal bowel gas in other conditions.

Abstract Monitoring widely distributed species on a budget presents challenges for the spatio‐temporal allocation of survey effort. When there are multiple discrete units to monitor, survey alternatives such as model‐based estimates can be useful to fill information gaps but may not reliably reflect biological complexity and change. The spatio‐temporal allocation of survey effort that minimizes uncertainty for the greatest number of units within a budget can help to ensure monitoring is optimized. We used aerial survey‐based population estimates of moose (Alces alces) across 30 Wildlife Management Units (WMUs) in Ontario, Canada to parameterize simulated populations and test the performance of different monitoring scenarios in capturing WMU‐specific annual variation and trends. Firstly, we tested scenarios that prioritized conducting a survey for a unit based on one of three management criteria: population state, population uncertainty or number of years between surveys. Also incorporated in the decision framework were WMU‐specific costs and annual budget constraints. Secondly, we tested how using model‐based estimates to fill information gaps improved population and trend estimates. Lastly, we assessed how the utility (based on minimizing population uncertainty) of using a model‐based estimate rather than conducting a survey was impacted by population density, severity of environmental stressors and years since the last survey. Interval‐based monitoring that minimized the number of years between surveys captured accurate trends for the highest number of WMUs, but annual variation was poorly captured regardless of management criteria prioritized. Using model‐based estimates to fill information gaps improved trend estimation. Further, the utility of conducting a survey increased with time since the last survey and was greater for populations with low densities when the severity of environmental stressors was high, while being greater for populations with high densities when environmental severity was low. Overall, the utility of aerial survey monitoring was strongly associated with WMU‐specific monitoring precision and the predictive power of model‐based estimates. If long‐term trends are evident, then there is greater value in using alternatives such as model‐based predictions to replace surveys, but model‐based estimates may be a poor substitute when there is strong annual variation and when using a simple model.

We constrain the multistage tectonic evolution of the Palaeoproterozoic UHT metamorphic (P ​= ​0.9–1.0 ​GPa, T >1000 ​°C, t ​= ​2088–2031 ​Ma) Bakhuis Granulite Belt (BGB) in Surinam on the Guiana Shield, using large- to small-scale structures, Al-in-hornblende thermobarometry and published fluid inclusion and zircon geochronological data. The BGB forms a narrow, NE–SW striking belt between two formerly connected, ~E–W oriented granite-greenstone belts, formed between converging Amazonian and West African continental masses prior to collision and Transamazonian orogeny. Inherited detrital zircon in BGB metasediments conforms agewise to Birimian zircon of West Africa and suggests derivation from the subsequently subducted African passive margin. Ultrahigh-temperature metamorphism may have followed slab break-off and asthenospheric heat advection. Peak metamorphic structures result from layer-parallel shearing and folding, reflecting initial transtensional exhumation of the subducted African margin after slab break-off. A second HT event involves intrusion, at ca. 0.49 ​GPa, of charnockites and metagabbros at 1993–1984 ​Ma and a layered anorthosite at 1980 ​Ma, after the BGB had already cooled to

Abstract Background Blunt traumatic gastric perforations in children are rare. Delayed diagnosis will lead to abdominal contamination and may result in morbidity and even mortality. We present a case of an adolescent who sustained blunt abdominal injury in a motocross accident and presented with remarkable hyperdense spherical shaped structures on the computed tomography (CT). Case presentation A 15-year-old boy arrived at the emergency room with an acute abdomen after a motocross accident. A CT scan of the abdomen demonstrated free air and hyperdense round structures in the stomach, pelvic cavity and right paracolic gutter. During emergency laparotomy a traumatic gastric perforation was sutured, a splenic rupture was treated with a vicryl mesh and multiple spherical food scraps were removed from the abdomen. After surgery, the boy clarified that he had eaten a whole bag of colorful and spherical shaped candy just before the accident. Conclusions Traumatic gastric rupture in children is rare but physicians should be aware of this diagnosis in case of blunt abdominal trauma with free air on the CT scan. Gastric contents, in this case candy, can present as hyperdense shaped structures in the abdominal cavity on the CT scan.