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Purpose: Surgical robotics have demonstrated their significance in assisting physicians during minimally invasive surgery. Especially, the integration of haptic and tactile feedback technologies can enhance the surgeon's performance and overall patient outcomes. However, the current state-of-the-art lacks such interaction feedback opportunities, especially in robotic-assisted interventional magnetic resonance imaging (iMRI), which is gaining importance in clinical practice, specifically for percutaneous needle punctures. Methods: The cable-driven 'Micropositioning Robotics for Image-Guided Surgery' (µRIGS) system utilized the back-electromotive force effect of the stepper motor load to measure cable tensile forces without external sensors, employing the TMC5160 motor driver. The aim was to generate a sensorless haptic feedback (SHF) for remote needle advancement, incorporating collision detection and homing capabilities for internal automation processes. Three different phantoms capable of mimicking soft tissue were used to evaluate the difference in force feedback between manual needle puncture and the SHF, both technically and in terms of user experience. Results: The SHF achieved a sampling rate of 800 Hz and a mean force resolution of 0.26 ± 0.22 N, primarily dependent on motor current and rotation speed, with a mean maximum force of 15 N. In most cases, the SHF data aligned with the intended phantom-related force progression. The evaluation of the user study demonstrated no significant differences between the SHF technology and manual puncturing. Conclusion: The presented SHF of the µRIGS system introduced a novel MR-compatible technique to bridge the gap between medical robotics and interaction during real-time needle-based interventions. [ABSTRACT FROM AUTHOR]

Sherpa is a general-purpose Monte Carlo event generator for the simulation of particle collisions in high-energy collider experiments. We summarise new developments, essential features, and ongoing improvements within the Sherpa 3 release series. Physics improvements include higher-order electroweak corrections, simulations of photoproduction and hard diffraction at NLO QCD, heavy-flavour matching in NLO multijet merging, spin-polarised cross section calculations, and a new model of colour reconnections. In addition, the modelling of hadronisation, the underlying event and QED effects in both production and decay has been improved, and the overall event generation efficiency has been enhanced. [ABSTRACT FROM AUTHOR]

Purpose: During the last few years, the number of electric scooter (e-scooter) users has risen to an all-time high. This study aimed to analyze e-scooter related accidents and trauma prevention measures in a large European city (Vienna, Austria). Methods: This retrospective study comprises a thorough data assessment and analysis of all e-scooter related accidents between 2018 and 2021 at a large level 1 trauma center in Vienna. Based on the data analysis, risk factors were identified, and possible prevention strategies were proposed. Results: During the observed period, 1337 patients sustained an injury from an e-scooter. Of these, 1230 were injured directly while driving (92%). The remaining 107 patients (8%) were classified as non-driving injuries. 927 injuries involved males (69.3%). The mean age was 32.1 years (range 4–86 years). Of all injured patients, 429 (32.1%) sustained at least one serious injury. The most common injuries included radial head fractures and concussions. Among the accidents treated, the use of protective equipment was sporadic. For example, helmets were worn in only 13.7% of cases. Wearing a helmet reduced the number of head injuries (24% versus 46.8%). In just three years, the number of patients increased 19-fold with a focus in the summer months. Conclusion: This study shows a substantial and sustained increase in e-scooter accidents with potentially serious injuries. Helmet use was found to be an effective form of head injury prevention. Further options for using protective equipment should be evaluated to improve the safety aspects of riding e-scooters. [ABSTRACT FROM AUTHOR]

Recent successes in developing small molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the recruitment of targets to LC3/GABARAP, a family of ubiquitin-like proteins that presumably bind to the autophagosome membrane and tether cargo-loaded autophagy receptors into the autophagosome. In this work, we rigorously tested the target engagement of the reported ATTECs to validate the existing LC3/GABARAP ligands. Surprisingly, we were unable to detect interaction with their designated target LC3 using a diversity of biophysical methods. Intrigued by the idea of developing ATTECs, we evaluated the ligandability of LC3/GABARAP by in silico docking and large-scale crystallographic fragment screening. Data based on approximately 1000 crystal structures revealed that most fragments bound to the HP2 but not to the HP1 pocket within the LIR docking site, suggesting a favorable ligandability of HP2. Through this study, we identified diverse validated LC3/GABARAP ligands and fragments as starting points for chemical probe and ATTEC development. Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but establish good ligandability of ATG8 isoforms through fragment screening and docking. [ABSTRACT FROM AUTHOR]

Purpose: Vertebral Body Tethering (VBT), an alternative treatment for adolescent idiopathic scoliosis, shows satisfactory post-operative results. However, the biomechanical quantities and consequences after VBT surgery remain largely unknown. Therefore, the aim of this study is to analyze the spinal biomechanics during different motions using a multibody simulation approach. Methods: The tether and intervertebral compression forces were simulated in a validated spine model during different physiological movements at different pre-tensions and screw positions, while considering the anatomical muscle and ligament properties. Results: The simulations showed that an augmentation of the pre-tension and an alteration of the screw position have both significant impact on the intervertebral compression and tether forces. The forces also vary depending on the movement performed, with the highest tether forces measured during lateral bending. In the upright position, with a pre-tension of 200 N, the maximum compression force increases by up to 157% compared to the untethered maximum compression force. The screw position can lead to large differences in the distribution of forces in the spine. Conclusion: The biomechanical data provide a first impression of the forces that occur along the spine during various physiological movements and are consistent with published clinical data. Forces are not evenly distributed along the spine, with higher lumbar forces. The tether forces reach values during lateral bending that can potentially destroy the tether´s integrity and thus may explain the common post-operative complication, namely tether breakage. The results of the model can therefore have an impact on future directions for improved surgical VBT treatment. [ABSTRACT FROM AUTHOR]

Purpose: Previous work comparing ASD to a normative population demonstrated that a large proportion of lumbar lordosis is lost proximally (L1-L4). The current study expands on these findings by collectively investigating regional angles and spinal contours. Methods: 119 asymptomatic volunteers with full-body free-standing radiographs were used to identify age-and-PI models of each Vertebra Pelvic Angle (VPA) from L5 to T10. These formulas were then applied to a cohort of primary surgical ASD patients without coronal malalignment. Loss of lumbar lordosis (LL) was defined as the offset between age-and-PI normative value and pre-operative alignment. Spine shapes defined by VPAs were compared and analyzed using paired t-tests. Results: 362 ASD patients were identified (age = 64.4 ± 13, 57.1% females). Compared to their age-and-PI normative values, patients demonstrated a significant loss in LL of 17 ± 19° in the following distribution: 14.1% had "No loss" (mean = 0.1 ± 2.3), 22.9% with 10°-loss (mean = 9.9 ± 2.9), 22.1% with 20°-loss (mean = 20.0 ± 2.8), and 29.3% with 30°-loss (mean = 33.8 ± 6.0). "No loss" patients' spine was slightly posterior to the normative shape from L4 to T10 (VPA difference of 2°), while superimposed on the normative one from S1 to L2 and became anterior at L1 in the "10°-loss" group. As LL loss increased, ASD and normative shapes offset extended caudally to L3 for the "20°-loss" group and L4 for the "30°-loss" group. Conclusion: As LL loss increases, the difference between ASD and normative shapes first occurs proximally and then progresses incrementally caudally. Understanding spinal contour and LL loss location may be key to achieving sustainable correction by identifying optimal and personalized postoperative shapes. [ABSTRACT FROM AUTHOR]

The recent success of the fusion ignition experiment at Lawrence-Livermore National Laboratory has renewed excitement for inertial confinement fusion. Designing such experiments relies on computational modeling using radiation hydrodynamic codes run on massively parallel supercomputers which simulate hydrodynamic flows, radiation diffusion, and thermonuclear burn. Constructing a quantum algorithm for radiation hydrodynamics that provides a quantum speedup is of great interest. A recent quantum algorithm that solves the Navier-Stokes equations of hydrodynamics with a quadratic speedup marks a first step towards this goal. Here we take the next step and present a quantum algorithm for nonlinear radiation diffusion that also has a quadratic speedup. To verify the algorithm we consider radiation striking a cold, optically thick target that generates a Marshak wave in the target. Results of numerical simulation of the quantum algorithm are compared with those of a standard partial differential equation solver and excellent agreement is found. [ABSTRACT FROM AUTHOR]

IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course. [ABSTRACT FROM AUTHOR]

Background: Apert syndrome is a congenital condition characterized by coronal craniosynostosis, ex-orbitism, midface hypoplasia as well as symmetric syndactyly of both feet and hands. Apert syndrome is linked by autosomal dominant inheritance to fibroblast growth factors receptor gene alteration. Case presentation: We present the case of a 20-month-old African boy who exhibited the characteristic facial features of Apert syndrome. Additionally, the child presented with syndactyly of both the fingers and toes. He was born to non-consanguineous parents, with the father being 33 years old at the time of the child's birth. A skull X-ray revealed an increased anteroposterior diameter of the skull, consistent with the cranial abnormalities associated with Apert syndrome. Further imaging of the hands and feet confirmed the pathognomonic syndactyly characteristic of the condition. The patient successfully underwent a series of surgeries to release the syndactyly in both his right and left hands. These surgical interventions have significantly improved the functionality of his hands. Conclusions: There is a paucity of information about Apert syndrome in Africa. Therefore, in order to enhance strong advocacy of this condition in Africa, more cases should be reported. [ABSTRACT FROM AUTHOR]

Over the last few decades the pharmaceutical industry has generated a vast corpus of knowledge on the safety and efficacy of drugs. Much of this information is contained in toxicology reports, which summarise the results of animal studies designed to analyse the effects of the tested compound, including unintended pharmacological and toxic effects, known as treatment-related findings. Despite the potential of this knowledge, the fact that most of this relevant information is only available as unstructured text with variable degrees of digitisation has hampered its systematic access, use and exploitation. Text mining technologies have the ability to automatically extract, analyse and aggregate such information, providing valuable new insights into the drug discovery and development process. In the context of the eTRANSAFE project, we present PretoxTM (Preclinical Toxicology Text Mining), the first system specifically designed to detect, extract, organise and visualise treatment-related findings from toxicology reports. The PretoxTM tool comprises three main components: PretoxTM Corpus, PretoxTM Pipeline and PretoxTM Web App. The PretoxTM Corpus is a gold standard corpus of preclinical treatment-related findings annotated by toxicology experts. This corpus was used to develop, train and validate the PretoxTM Pipeline, which extracts treatment-related findings from preclinical study reports. The extracted information is then presented for expert visualisation and validation in the PretoxTM Web App. Scientific Contribution While text mining solutions have been widely used in the clinical domain to identify adverse drug reactions from various sources, no similar systems exist for identifying adverse events in animal models during preclinical testing. PretoxTM fills this gap by efficiently extracting treatment-related findings from preclinical toxicology reports. This provides a valuable resource for toxicology research, enhancing the efficiency of safety evaluations, saving time, and leading to more effective decision-making in the drug development process. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disorder that affects multiple neurotransmitters, and its exact cause is still unknown. Developing new drugs for PD is a lengthy and expensive process, making it difficult to find new treatments. This study aims to create a detailed dataset to build strong predictive models with various machine learning algorithms. An ensemble modeling approach was employed to screen the DrugBank database, aiming to repurpose approved medications as potential treatments for Parkinson's disease (PD). The dataset was constructed using pIC50 values of various compounds targeting the inhibition of leucine-rich repeat kinase 2 (LRRK2). The best ensemble model showed exceptional predictive performance, with five-fold cross-validation and external validation metrics exceeding 0.8 (Q2cv = 0.864 and Q2ext = 0.873). The DrugBank screening resulted in three promising drugs—triamterene, phenazopyridine, and CRA_1801—with predicted pIC50 values greater than 7, warranting further investigation as novel PD treatments. Molecular docking and molecular dynamics simulations were performed to provide a comprehensive understanding of the interactions between LRRK2 and the inhibitors in the data set and best molecules of the screening. Free energy of binding calculation along with hydrogen bond occupancy analysis and RMSD of the ligand in the pocket show CRA_1801 as the best candidate to be repurposed as LRRK2 inhibitor. [ABSTRACT FROM AUTHOR]

We study a class of stochastic models of mass transport on discrete vertex set V. For these models, a one-parameter family of homogeneous product measures ⊗ i ∈ V ν θ is reversible. We prove that the set of mixtures of inhomogeneous product measures with equilibrium marginals, i.e., the set of measures of the form ∫ (⨂ i ∈ V ν θ i ) Ξ (∏ i ∈ V d θ i) is left invariant by the dynamics in the course of time, and the “mixing measure” Ξ evolves according to a Markov process which we then call “the hidden parameter model”. This generalizes results from De Masi et al. (Preprint , 2023) to a larger class of models and on more general graphs. The class of models includes discrete and continuous generalized KMP models, as well as discrete and continuous harmonic models. The results imply that in all these models, the non-equilibrium steady state of their reservoir driven version is a mixture of product measures where the mixing measure is in turn the stationary state of the corresponding “hidden parameter model”. For the boundary-driven harmonic models on the chain { 1 , … , N } with nearest neighbor edges, we recover that the stationary measure of the hidden parameter model is the joint distribution of the ordered Dirichlet distribution (cf. Carinci et al., Preprint , 2023), with a purely probabilistic proof based on a spatial Markov property of the hidden parameter model. [ABSTRACT FROM AUTHOR]

Background: Huntington disease (HD) is a progressive neurodegenerative disease that causes psychiatric and neurological symptoms, including involuntary and irregular muscle movements (chorea). Chorea can disrupt activities of daily living, pose safety issues, and may lead to social withdrawal. The vesicular monoamine transporter 2 inhibitors tetrabenazine, deutetrabenazine, and valbenazine are approved treatments that can reduce chorea. Objective: This post hoc analysis was conducted to evaluate safety and efficacy among participants who received high-dosage deutetrabenazine treatment (> 48 mg/d) in ARC-HD, an open-label study that assessed long-term safety and efficacy of deutetrabenazine for the treatment of chorea in HD in adults. Methods: ARC-HD was a single-arm, two-cohort, open-label study. Participants either successfully completed the First-HD study or switched overnight from tetrabenazine to deutetrabenazine. Participants were dosed with deutetrabenazine in a response-driven manner (maximum 72 mg/d allowed). For the current analysis, exposure-adjusted incidence rates (EAIRs) for adverse events of interest were analyzed according to daily dosage (≤ 48 mg/d versus > 48 mg/d), and total maximal chorea (TMC) scores were analyzed by cohort during the stable-dose period. Results: In total, 116 of the 119 participants enrolled in ARC-HD entered the stable-dose period, where no apparent differences were seen in EAIRs when receiving deutetrabenazine dosages ≤ 48 mg/d (exposure = 177.7 person-years) compared with > 48 mg/d (exposure = 74.1 person-years). Similar results were found among the subset of participants who received deutetrabenazine dosages > 48 mg/d at least once during the study (n = 49, 42%) when their dosage was ≤ 48 mg/d (exposure = 37.9 person-years) versus > 48 mg/d (74.1 person-years). Efficacy analyses were conducted for participants who had TMC scores available (rollover cohort, n = 77; switch cohort, n = 35). For most participants, the lowest deutetrabenazine dosage needed to achieve a TMC response (≥ 30% improvement from baseline) was between 24 and 48 mg/d in both the rollover (n = 57, 74.0%) and switch (n = 16, 46.0%) cohorts. Whereas the dosage needed for a TMC response was independent of baseline TMC score in the rollover cohort, participants with higher baseline TMC scores in the switch cohort required higher dosages to achieve a TMC response during the trial. Conclusions: In this open-label, long-term study, some participants received deutetrabenazine dosing > 48 mg/d to achieve adequate chorea control. There was no new safety concern or incremental change in the safety profile between dosages of ≤ 48 mg/d and > 48 mg/d. These results include dosages that have not been approved for clinical use, however, they increase our understanding of safety and tolerability of deutetrabenazine doses. Clinical Trials Registration: ARC-HD (ClinicalTrials.gov identifier: NCT01897896); First-HD (ClinicalTrials.gov identifier: NCT01795859). Plain Language Summary: ARC-HD was a medical study in which participants took a medicine called deutetrabenazine. Deutetrabenazine is used to treat unplanned movements known as chorea, which happen in participants who have Huntington disease. At the start of the ARC-HD study, all participants took 6 milligrams per day (mg/d) of the medicine. Each week, the doctor could give them more medicine, but not more than 72 mg/d. The doctor checked if the medicine helped to lower their chorea and if any safety concerns occurred. The highest amount of the medicine that is allowed in the USA is 48 mg/d. Some participants took more than that. We wanted to learn more about the safety (side effects) and the chorea in participants who took more than 48 mg/d. Participants who took more than 48 mg/d had no new side effects of interest. They also reported the same number of side effects as participants who took 48 mg/d or less. For most participants, the lowest amount of medicine they needed to lower their chorea was between 24 and 48 mg/d. [ABSTRACT FROM AUTHOR]

By the Aharonov–Casher theorem, the Pauli operator P has no zero eigenvalue when the normalized magnetic flux α satisfies | α | < 1 , but it does have a zero energy resonance. We prove that in this case a Lieb–Thirring inequality for the γ -th moment of the eigenvalues of P + V is valid under the optimal restrictions γ ≥ | α | and γ > 0 . Besides the usual semiclassical integral, the right side of our inequality involves an integral where the zero energy resonance state appears explicitly. Our inequality improves earlier works that were restricted to moments of order γ ≥ 1 . [ABSTRACT FROM AUTHOR]

Introduction: Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year. Methods: RESTORE is a multicenter, open-label randomized controlled trial. Candidates were assessed for CLBP associated with multifidus dysfunction, with no indication for or history of lumbar spine surgery. Participants were randomized to either restorative neurostimulation with the ReActiv8 system or OMM. The primary endpoint was a comparison of the mean change in the Oswestry Disability Index (ODI) between the treatment and control arms at 1 year, and secondary endpoints included pain (numeric rating scale [NRS]) and health-related quality of life (EuroQol Five-Dimension [EQ-5D-5L]). Results: A total of 203 patients, average age 47 years, and with an average 11-year history of low back pain, were included in the analysis. The primary endpoint was a statistically significant demonstration of a clinically relevant mean improvement in the Oswestry Disability Index (ODI) between restorative neurostimulation and OMM arms: ODI (−19.7 ± 1.4 vs. −2.9 ± 1.4; p < 0.001). Additionally, improvements in both the numeric rating scale (NRS) (−3.6 ± 0.2 vs. −0.6 ± 0.2; p < 0.001) and EuroQol Five-Dimension (EQ-5D-5L) (0.155 ± 0.012 vs. 0.008 ± 0.012; p < 0.001) were statistically and clinically significant in the restorative neurostimulation arm compared to the OMM arm. Conclusion: The RESTORE trial demonstrates that restorative neurostimulation is a safe, reversible, clinically effective, and highly durable option for patients suffering with nonoperative CLBP associated with multifidus dysfunction. This demonstration of treatment superiority over OMM through 1 year is a significant milestone in addressing a major health burden and unmet clinical need. Trial Registration: ClinicalTrials.gov Identifier: NCT04803214. Plain Language Summary: Chronic low back pain can occur as a consequence of dysfunction in the key stabilizing muscles of the spine, the multifidi. This type of low back pain is difficult to treat, with many interventions resulting in limited improvement or short-term relief for a significant proportion of patients. Despite this limitation, these approaches still represent the best available care in most practices. Restorative neurostimulation is a technique that stimulates dysfunctional multifidi, overriding muscle inhibition to improve spinal function, reduce disability, and alleviate pain. The hypothesis was that this treatment is appropriate for a specific subset of patients who have failed to respond to best available conservative and interventional care. The goal of this study was to compare the effect of restorative neurostimulation to standard-of-care interventions (optimal medical management) for patients with chronic mechanical low back pain. Patients with an average 11-year history of chronic low back pain and diagnosed with multifidus dysfunction were randomly assigned to either ongoing optimal medical management or restorative neurostimulation. At 1 year, disability, pain, and healthcare-related quality of life were assessed. Patients treated with restorative neurostimulation demonstrated significant improvements in their clinical outcomes compared to those receiving optimal medical management alone. Device-related adverse events were rare, reinforcing the safety profile of this technique. This study demonstrated that without restorative neurostimulation, patients with chronic low back pain and multifidus dysfunction have very few effective options and obtained little clinical benefit from ongoing optimal medical management. Restorative neurostimulation is an important advancement for this difficult-to-treat population. [ABSTRACT FROM AUTHOR]

Background: Since obesity has emerged as a major public health concern, there is an urgent need to better understand factors related to weight gain and treatment success. Methods: This study included 118 persons with obesity who participated in a multidisciplinary combined lifestyle intervention with cognitive-behavioral therapy at the outpatient clinic of the Obesity Center CGG at Erasmus University Medical Center, Rotterdam, The Netherlands. Neighborhood characteristics were assessed using a 13-item questionnaire. Multiple regression analyses were performed to examine the association between perceived safety, social cohesion, and the availability of facilities on relative changes in body mass index and waist circumference changes, adjusted for corresponding neighborhood socioeconomic status scores. Results: Higher total scores, indicating more unfavorable neighborhood perceptions, were associated with less relative improvements in BMI and waist circumference after 1.5 years (β = 3.2, 95%CI 0.3–6.0; β = 3.4, 95%CI 0.3–6.6, respectively). Also, more neighborhood unsafety was associated with less relative improvements in BMI and waist circumference on the long term (β = 3.1, 95%CI 1.1–5.1; β = 2.8, 95%CI 0.6–5.1, respectively). Conclusion: The results indicate that living in a neighborhood perceived as less favorable may lower the chances of successful weight loss in response to combined lifestyle interventions in persons with obesity. [ABSTRACT FROM AUTHOR]

The creation of a common European currency has been scrutinized in the context of optimum currency area theory since its origin in Mundell (1961). The debate gained particular prominence in light of the endogeneity hypothesis (Frankel and Rose 1998), which argues that once two countries establish a common currency, their economic structures and cycles increasingly align due to strengthening intra-industry trade. By contrast, the specialization hypothesis (Eichengreen 1992; Krugman and Venables 1996) argues that the creation of a currency union will predominantly increase inter-industry trade, ultimately lowering business cycle correlation. To test these views, we establish several indices of bilateral trade intensity across EU members using input–output data, measuring gross and so-called value-added trade, which also considers the contribution of intermediary goods in the production of final exports. The results of the fixed effect panel data framework indicate a strong and robust empirical relationship between growth correlations and intra-industry trade, much in line with both Mundell's and Frankel and Rose's theories. However, we cannot establish a similarly robust relationship between total trade intensity and growth correlations. We reconcile these results by identifying a statistically significant relationship between economic alignment and trade when only considering industrial production, highlighting the importance of pan-European industrial supply chains for European economic integration. Rerunning our regression framework on the subsample of the eurozone indicates that the common currency area displayed even stronger properties of an optimum currency area than the entire European Union. [ABSTRACT FROM AUTHOR]

Purpose: Over half of hormone receptor-positive (HR+) breast cancer recurrences occur >5 years from diagnosis, however, little is known about well-being or breast cancer risk perceptions and knowledge in long-term HR+ breast cancer survivors. Methods: From 1/2021 to 1/2022, we surveyed patients with a history of stage II/III, HR+ breast cancer, ≥5 years from diagnosis, without recurrence about concerns and perceptions related to their diagnosis and recurrence risk, physical and emotional health, knowledge, and risk reduction. Logistic regression identified factors associated with overestimation of 5–10 year distant recurrence risk. Results: Among 166 women, median age at diagnosis was 51, 2.4% were Black and 1.2% Hispanic; 19.3% did not have a college degree. Median time from diagnosis was 10 years (range: 5–23). Median PROMIS anxiety (53; range: 37–73), physical (51, range: 32–68), and mental (51, range: 25–68) scores were similar to population norms (score of 50). 40% of women estimated metastatic recurrence risk to be ≥20% 5–10 years post-treatment; patients without a college degree were more likely to overestimate this risk (multivariable prevalence odds ratio: 3.69, 95% confidence interval: 1.49, 9.18). Only 17% correctly indicated HR+ breast cancer as having a higher risk of recurrence after 5 years; over one-third inaccurately responded that alcohol in moderation decreases recurrence risk. Conclusion: While physical and emotional health were comparable to the general population, many survivors harbored inaccurate risk perceptions and knowledge. The association between lower educational attainment and risk overestimation underscores the importance of attention to literacy and numeracy when developing interventions to improve risk communication. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Digitally Enhanced Hands-on Surgical Training (DEHST) platform was introduced to overcome the lack of training capabilities for the challenging task of freehand distal interlocking of intramedullary nails. It demonstrates high perceived realism for surgeons, and novices perform significantly better after DEHST training. However, characterization of how performance improves remained unexplored. The aim of this study was to evaluate the training progression of novices in freehand distal interlocking during five training rounds with DEHST and to compare their performance in a simulated operation against experienced surgeons. Methods: Ten novices (Group 1) underwent five DEHST training sessions (approximately one hour in total) and their performance data was acquired and evaluated. The surgical performance of Group 1 was compared with ten surgical experts (Group 2) by performing distal interlocking of a real tibia nail in an artificial bone model in a simulated operation. Time taken, number of X-rays, accuracy of nail hole roundness, and success rates were compared between the groups. Results: Group 1 achieved comparable performance to Group 2 in number of X-rays 26.0 (range 15–40) versus 22.5 (range 16–34), p = 0.281, and accuracy of hole roundness 95.0% (range 91.1–98.0%) versus 93.3% (range 90.7–95.9%), p = 0.087. However, Group 1 needed significantly longer time compared with Group 2, p = 0.001, and furthermore, one participant in Group 1 (10%) failed to hit the nail hole with the drill bit, while 100% of the participants in Group 2 were successful. Conclusions: DEHST appears to be a useful tool to gradually improve the proficiency level of novices and to train relevant practical surgical skills needed for distal interlocking of intramedullary nails. However, further investigations are needed to demonstrate the performance under the conditions of a real operation. [ABSTRACT FROM AUTHOR]

Purpose: Thoracic trauma causes pain and hospitalisation. Middle- and high-income countries have different trauma contexts and populations. To report patients’ clinical presentation (pain and shortness of breath) and its influence on hospital length of stay (LOS), acute care management, and discharge destinations in South Africa (SA) and Sweden. Methods: Prospective observational multicenter study by means of clinical record review. Two centers in SA and four centers in Sweden participated. One thousand nine hundred and eighteen adults with thoracic trauma were screened over the 20 months period. Study objectives guided information retrieved from clinical records. Statistical analysis was done with significance at p-value < 0.05. Results: Three-hundred-sixty-four participants were recruited with most being male (n = 170/179 (95%) SA; n = 125/185 (68%) Sweden). Type and mechanism of injury differed (SA penetrating (82%) versus Sweden blunt (95%); SA assaults (90%) versus Sweden falls (44%)). Unilateral haemopneumothorax was common (SA 68%, Sweden 35%) and managed with intercostal drainage. Rib cage injuries were common in the Swedish cohort with rib fixation surgery for 17%. Physiotherapy treatment frequency was mostly daily. Blunt injury resulted in higher pain levels during deep breathing (day 1: p = 0.014; day 2: p < 0.001; day 3: p < 0.001) and shortness of breath during activity (day 1: p = 0.036; day 2: p = 0.003; day 3: p < 0.001). LOS was shorter for SA cohort (5 (± 4) versus 7 (± 5) days; p = 0.024). Age influenced LOS in the blunt injury group. Discharge destination was mostly home (99% SA, 56% Sweden). Conclusion: Priority care is indicated for those who are older and have blunt thoracic injury to prevent pulmonary complications and prolonged hospitalisation. [ABSTRACT FROM AUTHOR]

Purpose: In polytrauma patients, injuries involving the extremities are frequently seen. Treatment concepts vary from early definitive care to temporary fixation and delayed definite stabilization. This analysis therefor aims to illuminate the impact of timing for operative stabilization of extremity fractures on outcome factors in adult polytrauma patients. Methods: We searched PubMed and Cochrane CENTRAL to identify studies from inception of each database to 14 September 2022. We included systematic reviews and RCTs comparing immediate versus delayed operative fracture stabilization and early definite care versus primary external fixation in adult polytrauma patients. Results: Five randomized controlled trials were included, with a total of 335 patients. The analysis found no statistically significant difference in overall mortality or improvement in ICU admission between early (< 24 h) and late fracture stabilization. Comparing femoral nailing and external fixation, findings showed that femoral nailing reduce ICU length of stay and duration of invasive mechanical ventilation. Conclusion: The results indicate that immediate surgical treatment by nailing is superior to delayed treatment or a staged surgical approach in stable polytrauma patients with long-bone fractures. As there is a lack of clear evidence regarding the optimal timing for definitive operative stabilization of extremity fractures in polytrauma patients, further high-quality studies are essential to enhance the certainty of evidence and provide more conclusive treatment algorithms. [ABSTRACT FROM AUTHOR]

Purpose: Distal radius fractures (DRFs) are often initially assessed by junior doctors under time constraints, with limited supervision, risking significant consequences if missed. Convolutional Neural Networks (CNNs) can aid in diagnosing fractures. This study aims to internally and externally validate an open source algorithm for the detection and localization of DRFs. Methods: Patients from a level 1 trauma center from Adelaide, Australia that presented between 2016 and 2020 with wrist trauma were retrospectively included. Radiographs were reviewed confirming the presence or absence of a fracture, as well as annotating radius, ulna, and fracture location. An internal validation dataset from the same hospital was created. An external validation set was created with two other level 1 trauma centers, from Groningen and Rotterdam, the Netherlands. Three surgeons reviewed both sets for DRFs. Results: The algorithm was trained on 659 radiographs. The internal validation set included 190 patients, showing an accuracy of 87% and an AUC of 0.93 for DRF detection. The external validation set consisted of 188 patients, with an accuracy and AUC were 82% and 0.88 respectively. Radial and ulnar bone segmentation on the internal validation was excellent with an AP50 of 99 and 98, but moderate for fracture segmentation with an AP50 of 29. For external validation the AP50 was 92, 89 and 25 for radius, ulna, and fracture respectively. Conclusion: This open-source algorithm effectively detects DRFs with high accuracy and localizes them with moderate accuracy. It can assist clinicians in diagnosing suspected DRFs and is the first radiograph-based CNN externally validated on patients from multiple hospitals. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the prevalence, impact and change of the symptoms after implant removal due to irritation in multiple rib fractures. This study aims to explore these aspects to improve treatment decision-making. Methods: Data was collected from two hospitals in the Netherlands and Switzerland. The study included only adults with operatively treated multiple rib fractures, regardless of whether the fractures were flail or non-flail. The primary outcome was the incidence of implant removal due to irritation. Secondary outcomes included implant irritation not leading to removal, other postoperative complications, and remission rates after implant removal. These outcomes were assessed during a follow-up phone call using a standardized questionnaire. Results: Hundred-twenty patients were identified, with 83 (69.2%) completing the final follow-up after a median of 49 months (IQR 40–59). Twenty-five (30.1%) patients experienced implant irritation, of whom four (4.8%) got their implant removed. Two (2.4%) reported significant improvement, one (1.2%) moderate, and one (1.2%) no improvement of symptoms. Conclusion: Implant irritation in patients with multiple rib fractures is a common problem, even years after surgery, without guaranteed symptom improvement post-removal. These results provide an additional argument to be more selective in offering rib fixation to patients with multiple rib fractures in the first place. [ABSTRACT FROM AUTHOR]

The adult electric organ in weakly electric mormyrid fish consists of action-potential-generating electrocytes, structurally and functionally modified skeletal muscle cells. The electrocytes have a disc-shaped portion and, on one of its sides, numerous thin processes, termed stalklets. These unite to stalks leading to a single main stalk that carries the innervation site. Here, we describe the 3-dimensional layout of the stalklet/stalk system in adult Campylomormyrus compressirostris by differential interference contrast microscopy and confocal fluorescence microscopy. Using antibodies against Na+/K+-ATPase α-subunit and plasma membrane Ca2+-ATPase, we show that these ion pumps are differentially distributed over the stalklet/stalk system, with plasma membrane Ca2+-ATPase being enriched on the stalklet membrane. Stalklets are distributed and organized in a quite uniform pattern on the posterior face of the electrocyte disc and fuse to terminal stalks. The latter then unite in a mostly dichotomic mode to stalks of increasing thickness, with the main stalk measuring about 100 µm in diameter. We further analyse the structural organization of stalklets and stalks, with a characteristic cytoskeletal system of bundled actin filaments in the centre and nuclei in subsurface position. These results suggest that the stalklet/stalk system is adapted in its structural layout to generate an action potential highly synchronized over the entire disc-portion of the electrocyte, accounting for the short electric organ discharge in this species. Our results suggest that actin-related proteins overexpressed in electrocytes, as shown previously by transcriptome analysis, may be involved in the organization of the unique F-actin system in stalklets and stalks. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC) is a rare cancer that most commonly occurs in the salivary glands, making up approximately 2–4% of all head and neck malignancies. Treatment for ACC varies, with combinations of surgical excision, adjuvant radiotherapy, and chemotherapy reported in the literature. In this study, we aim to assess ACC recurrence rates with Mohs Micrographic Surgery (MMS) treatment compared to traditional wide local excision (WLE). In June of 2024, a comprehensive review of the literature was performed using the following keywords: "Adenoid Cystic Carcinoma" and/or "Mohs Micrographic Surgery" and/or "MMS" and/or "excision." Between the two databases, 25 articles were identified which included a total of 30 patients. Among all the articles, 30 procedures were documented — 8 MMS and 22 WLE. Patients with ACC treated with WLE had a higher rate of recurrence (40.9%) compared to those treated with MMS (12.5%). Limitations include a small number of tumors treated and reporting bias. MMS for the treatment of ACC demonstrated a decreased recurrence rate compared to WLE. Further studies with larger sample sizes are needed to confirm the benefit of MMS over WLE. [ABSTRACT FROM AUTHOR]

The Surface Dust Analyser (SUDA) is a mass spectrometer onboard the Europa Clipper mission for investigating the surface composition of the Galilean moon Europa. Atmosphereless planetary moons such as the Galilean satellites are wrapped into a ballistic dust exosphere populated by tiny samples from the moon's surface produced by impacts of fast micrometeoroids. SUDA will measure the composition of such surface ejecta during close flybys of Europa to obtain key chemical signatures for revealing the satellite's composition such as organic molecules and salts, history, and geological evolution. Because of their ballistic orbits, detected ejecta can be traced back to the surface with a spatial resolution roughly equal to the instantaneous altitude of the spacecraft. SUDA is a Time-Of-Flight (TOF), reflectron-type impact mass spectrometer, optimized for a high mass resolution which only weakly depends on the impact location. The instrument will measure the mass, speed, charge, elemental, molecular, and isotopic composition of impacting grains. The instrument's small size of 268 mm × 250 mm × 171 mm , radiation-hard design, and rather large sensitive area of 220 cm2 matches well the challenging demands of the Clipper mission. [ABSTRACT FROM AUTHOR]

We prove a parametric jet interpolation theorem for symplectic holomorphic automorphisms of C 2 n with parameters in a Stein space. Moreover, we provide an example of an unavoidable set for symplectic holomorphic maps. [ABSTRACT FROM AUTHOR]

Objectives: In patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the response to treatment is evaluated based on microbiological, clinical, and radiological data. However, little is known about the dynamics of CT findings. The aim of this study was to evaluate CT changes in NTM-PD in order to define radiological criteria for treatment success. Methods: Retrospective multicenter study (Hannover, Heidelberg, Gauting). Sixty patients with NTM-PD and at least two consecutive CT scans were included. Scoring for NTM-PD was performed by evaluating variables of bronchiectasis, mucus plugging, bronchiolitis, cavities, nodules, and consolidations on an ordinal scale from 0 to 3. Differences between baseline and follow-up were calculated, and patients with/without cultural conversion were compared using the Mann–Whitney U-test. For paired comparison of the two consecutive CT scans the Wilcoxon test was used. Results: Comparing patients with and without culture conversion, there were significant differences in temporal changes of bronchiectasis (p < 0.001), cavities (p = 0.006), bronchiolitis (p < 0.001), consolidations (p = 0.004), and total score (p < 0.001). Nodules showed no significant differences between groups (p = 0.060). The Wilcoxon test showed significant differences between both CTs in patients with a microbiological cure for the total score (p < 0.001), cavities (p = 0.005), bronchiolitis (p < 0.001), and consolidations (p = 0.021) with a decrease after microbiological cure, whereas bronchiectasis (p = 0.102) and nodules (p = 0.18) stayed stable. In the case of persistently positive cultures, there was an increase in the total score (p = 0.010) which was attributable to progressive bronchiectasis (p < 0.001). Conclusion: Cavities, consolidations, and bronchiolitis are useful to assess treatment response, whereas bronchiectasis and nodules may remain stable despite successful treatment. Clinical relevance statement: Cavities, consolidations, and bronchiolitis can assess treatment response whereas bronchiectasis and nodules may remain stable despite successful treatment. In persistently positive cultures, bronchiectasis showed an increase over time indicating that NTM-PD is a progressive chronic disease. Key Points: Little is known about CT changes in nontuberculous mycobacteria pulmonary disease (NTM-PD) and criteria to evaluate treatment response. In the case of culture conversion, cavities and bronchiolitis decreased whereas bronchiectasis and nodules remained stable. Cavities and bronchiolitis can evaluate treatment response in NTM, but bronchiectasis and nodules may persist despite successful treatment. [ABSTRACT FROM AUTHOR]

Objectives: 3D phase-resolved functional lung (PREFUL) MRI offers evaluation of pulmonary ventilation without inhalation of contrast agent. This study seeks to compare ventilation maps obtained from 3D PREFUL MRI with a direct ventilation measurement derived from 129Xe MRI in both patients with chronic obstructive pulmonary disease (COPD) and healthy volunteers. Methods: Thirty-one patients with COPD and 12 healthy controls underwent free-breathing 3D PREFUL MRI and breath-hold 129Xe MRI at 1.5 T. For both MRI techniques, ventilation defect (VD) maps were determined and respective ventilation defect percentage (VDP) values were computed. All parameters of both techniques were compared by Spearman correlation coefficient (r) and the differences between VDP values were quantified by Bland–Altman analysis and tested for significance using Wilcoxon signed-rank test. In a regional comparison of VD maps, spatial overlap and Sørensen–Dice coefficients of healthy and defect areas were computed. Results: On a global level, all 3D PREFUL VDP values correlated significantly to VDP measure derived by 129Xe ventilation imaging (all r > 0.65; all p < 0.0001). 129Xe VDP was significantly greater than 3D PREFUL derived VDPRVent (mean bias = 10.5%, p < 0.001) and VDPFVL-CM (mean bias = 11.3%, p < 0.0001) but not for VDPCombined (mean bias = 1.7%, p = 0.70). The total regional agreement of 129Xe and 3D PREFUL VD maps ranged between 60% and 63%. Conclusions: Free-breathing 3D PREFUL MRI showed a strong correlation with breath-hold hyperpolarized 129Xe MRI regarding the VDP values and modest differences in the detection of VDs on a regional level. Clinical relevance statement: 3D PREFUL MRI correlated with 129Xe MRI, unveiling regional differences in COPD defect identification. This proposes 3D PREFUL MRI as a ventilation mapping surrogate, eliminating the need for extra hardware or inhaled gases. Key Points: Current non-invasive evaluation techniques for lung diseases have drawbacks;129Xe MRI is limited by cost and availability. 3D PREFUL MRI correlated with129Xe MRI, with regional differences in identifying COPD defects. 3D PREFUL MRI can provide ventilation mapping without the need for additional hardware or inhaled gases. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Herz-, Thorax- und Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Purpose: Cancer-related cognitive impairment (CRCI) can have a profound impact on the lives of cancer survivors. A multitude of subjective and objective assessment tools exist to assess the presence and severity of CRCI. However, no purpose-built tool exists to assess the unmet needs of cancer survivors directly relating to CRCI. This paper details the development and initial validation of the Multinational Association of Supportive Care in Cancer - Unmet Needs Assessment of Cancer-Related Cognitive Impairment Impact (the MASCC COG-IMPACT). Methods: A multistep mixed-methods measurement development and validation approach was taken with a strong emphasis on co-design. Qualitative interviews were conducted with cancer survivors (n = 32) and oncology health professionals (n = 19), followed by a modified Delphi survey with oncology health professionals (n = 29). Cognitive interviews with cancer survivors (n = 22) over two rounds were then conducted to finalise the penultimate version of the unmet needs assessment tool for CRCI. Four-hundred and ninety-one (n = 491) cancer survivors then completed the MASCC COG-IMPACT and other established measures to inform structural, reliability, validity, acceptability, appropriateness, and feasibility analyses. Results: The final MASCC COG-IMPACT is a 55-item and eight subscale tool including two indices: “difficulties” and “unmet needs”. The MASCC COG-IMPACT was found to have strong structural validity, convergent validity, discriminant validity, internal consistency, and test–retest reliability. The MASCC COG-IMPACT was also found to be highly acceptable, appropriate, and feasible. Conclusion: The MASCC COG-IMPACT may facilitate optimal care and referral in line with a cancer survivor’s CRCI-related difficulties and unmet needs. The MASCC COG-IMPACT may also be used to explore factors and contributors to CRCI-related difficulties and unmet needs. Overall, the MASCC COG-IMPACT is a highly reliable and valid tool for the assessment of CRCI-related difficulties and unmet needs in both clinical and research settings. The MASCC COG-IMPACT and supporting materials can be accessed on the MASCC webpage or via the MASCC COG-IMPACT Open Science Framework webpage (). [ABSTRACT FROM AUTHOR]

Purpose: While surgical intervention of scoliosis in cerebral palsy (CP) patients has shown notable improvements in quality of life, the high risk of post-operative complications in CP patients necessitates careful preoperative optimization. A preoperative multidisciplinary (Multi-D) pathway at our tertiary pediatric hospital in effect since 2014 led to a significant reduction in mortality at one year. However, such a strategy delays surgery, potentially increasing the risk of curve progression. This study aims to elucidate the impact of the Multi-D screening process on curve progression in neuromuscular scoliosis among complex CP patients. Methods: A retrospective review of all CP patients with scoliosis at a tertiary care center from 2012 to 2020 was conducted. This assessment focused on the progression of the major Cobb angle from the time of the indications conference to surgery of patients who went through Multi-D screening. Patient demographics and perioperative variables were obtained from the electronic medical record (EPIC, Systems Verona, WI). Results: After exclusion criteria were met, there were 85 patients who went through Multi-D, 78 of whom had surgery, and seven who did not. Surgery was delayed an average of 202 days for Multi-D optimization. We found a trend in increasing Cobb angle over time, but this correlation did not reach statistical significance (p = 0.079). 45 Multi-D surgery participants had a decrease or no change in Cobb angle and had surgery an average of 5.6 months after indications. 33 Multi-D surgery participants had an increase in Cobb angle and had surgery an average of 8.5 months after indications. Cobb angle progressed an average of 13.4° in the increased group, and − 0.4° in the decrease or no change group. There were no associations with change in Cobb angle and GMFCS, starting major curve angle, number of referrals, or intrathecal baclofen pump use according to this analysis. Conclusions: Multi-D optimization resulted in an average delay in surgery of 6.7 months. Patients that did not have a change in Cobb angle had surgery within 5.6 months vs. patients that had an increase in Cobb angle had surgery on average 8.5 months after indicated for surgery, with an average increase of Cobb angle of 13.4°. Level of evidence: Level III, retrospective comparative study. [ABSTRACT FROM AUTHOR]

We assessed the global incidence, mortality, and disability-adjusted life years (DALYs) associated with various liver diseases, including alcohol-related liver disease (ALD), hepatitis B/C virus infections (HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index (SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD, along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States (U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world. [ABSTRACT FROM AUTHOR]

Background: Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases. Material and methods: In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan–Meier estimates and Cox proportional hazards regression. Results: Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38–48%] compared to 32% [95% CI 29–35%] in TTF-1 positive (TTF-1 +) patients (p < 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18–31 mL]) vs. 15 mL [95% CI 12–17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45–70 mL]) vs. 84 mL [95% CI 73–94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression. Conclusion: In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype. [ABSTRACT FROM AUTHOR]

Structural performance of timber buildings can be adversely affected by exposed harsh environment and sustained load. This study investigates bending performance degradation of glued laminated timber (GLT) beams (50 mm × 50 mm × 950 mm) that are exposed to unfavorable environmental conditions. The experiments consider eight scenarios, including various climate cycling periods, duration, and stress levels. Eight groups of GLT beams were exposed to the different scenarios for four stages, then loaded by short-term bending to obtain the MOR and MOE. The results showed that coupling effects of sustained loading and the environmental factors such as UV-light and mist spraying aggravated the pronounced damage on the laminates and gluelines and caused the degradation of strength and stiffness. The highest degradation rate occurred in the first stage. In the relatively mild environments, some performance recovery was observed in the later stages, most specimens exhibited ductile failure accompanied by the significant increase of the ultimate deflection with the exposure time. While in the harsh environments, the MOR and MOE degradation was evident and continuous, more specimens experienced brittle failure, and the increase of the ultimate deflection slowed down greatly with the exposure time. Additionally, the effects of sustained loading period were significantly exacerbated under the harsh environmental conditions, the specimens loaded by less than 50% stress level exhibited the distinguished degradation in 24 days. [ABSTRACT FROM AUTHOR]

Urban river pollution has become a critical sustainability challenge worldwide. In the studies of urban river pollution, very little research focus has gone into understanding pollution effects on main river-dependent livelihoods among marginal communities in urban centres. In this study, using a context-specific risk framework, we identify and analyze (i) urban river-dependent livelihoods (ii) pathways to community exposure to urban river pollution (iii) effects and consequences on urban river-dependent livelihoods (iv) potential intervention strategies. The study uses knowledge co-production workshops, and ethnographic methods involving participant observations, focus group discussions, in-depth interviews, and key informant interviews as a means of generating the needed data. Our findings indicate that degraded urban rivers have had profound negative effects on river-dependent livelihoods such as food processing, poultry, livestock farming and the small-scale brick industries for construction. Further, urban river pollution has also led to livelihood-related conflicts over access to limited, good-quality water resources. Intervention strategies to improve livelihood resilience are suggested at the institutional, communal and livelihood levels. Institutional interventions include strengthening environmental laws compliance and enforcement, inter-agency collaborations and extending sanitation and urban planning to marginal communities in cities. Communal interventions are sensitization campaigns, enforced sanitation practices and calls for behavioural and attitudinal change. Livelihoods-linked interventions aim to reduce livelihood strategies’ contributions to river pollution. Such interventions include proper disposal of waste generated through livelihood strategies, and instituting practices that minimize run-off from wet industries. [ABSTRACT FROM AUTHOR]

Finding a robust and efficient solver for (non-)symmetric systems that arise in incompressible Computational Fluid Dynamics (CFD) is of great interest to both academia and industry. We consider the Compatible Discrete Operator (CDO) discretization that has recently been devised for CFD simulations in the context of incompressible Stokes and Navier–Stokes flows. The discrete problems resulting from CDO schemes yield large saddle-point systems that require relevant numerical methods suitable to deal with large indefinite and poorly conditioned linear systems. In this paper, we focus on two segregated methods: the augmented Lagrangian Uzawa method and the generalized Golub–Kahan bidiagonalization, as well as a monolithic method based on an algebraic transformation by change of variables. We also employ algebraic multigrid (AMG) preconditioned Krylov solvers such as the Flexible Conjugate Gradient (FCG) method, and the Flexible Generalized Minimal Residual (FGMRES) method, to solve the linear systems. Using the CFD software code_saturne, we compare the numerical performance with respect to the choice of linear solvers and numerical strategies for the saddle-point problem. In the numerical experiments, the AMG preconditioned Krylov methods show robustness in test cases of Stokes and Navier–Stokes problems. [ABSTRACT FROM AUTHOR]

Many estimators of the variance of the well-known unbiased and uniform most powerful estimator of the Mann–Whitney effect, are considered in the literature. Some of these estimators are only valid in cases of no ties or are biased in small sample sizes where the amount of bias is not discussed. Here, we derive an unbiased estimator based on different rankings, the so-called ’placements’ (Orban and Wolfe in Commun Stat Theory Methods 9:883–904, 1980), which is therefore easy to compute. This estimator does not require the assumption of continuous distribution functions and is also valid in the case of ties. Moreover, it is shown that this estimator is non-negative and has a sharp upper bound, which may be considered an empirical version of the well-known Birnbaum–Klose inequality. The derivation of this estimator provides an option to compute the biases of some commonly used estimators in the literature. Simulations demonstrate that, for small sample sizes, the biases of these estimators depend on the underlying distribution functions and thus are not under control. This means that in the case of a biased estimator, simulation results for the type-I error of a test or the coverage probability of a confidence interval do not only depend on the quality of the approximation of by a normal distribution but also an additional unknown bias caused by the variance estimator. Finally, it is shown that this estimator is L 2 -consistent. [ABSTRACT FROM AUTHOR]

Key message: Deeper groundwater tables restrict taller, slenderer tree forms, pinpointing the importance of hydraulic path length presumably dictated by groundwater depth in regulating tree growth and architecture. How tree dimensions are interrelated (i.e., allometry) is a key question in biomechanics and forest ecology. Yet, the functional significance of tree allometry in coping with groundwater availability in drylands has been rarely explored. This gap of knowledge is particularly acute for riparian forests in Central Asia (known as Tugay forests), where groundwater table depth (GWD) is one of the most limiting factors. Based on the rationale of the hydraulic constraint hypothesis in explaining tree height growth, we posited that GWD should dictate hydraulic path length and eventually limit height (H) more than diameter (D) growth. Therefore, we predicted that there would be a lower increment in H with a unit increment in D (i.e., a small scaling exponent), or lower H at a given D, above deeper groundwater tables. Here we gathered a dataset of paired H–D measures for > 6500 trees of Populus euphratica, a keystone phreatophyte species of riparian Tugay forests, along a gradient of GWD from 1.5 m to 10 m across 16 sites in the Tarim River corridor (NW China). We quantified the H–D allometries at individual sites using standardized major axis regression, and tested for any significant shift in scaling exponents or expected H at a given D in relation to GWD. Results showed that the H–D scaling exponents in P. euphratica varied widely across sites, with an average of 0.65 (i.e., H ∝ D0.65) close to the “canonical” value of 2/3 as posited by theory. With increasing GWD, the scaling exponents did not vary predictably, but the expected H at the grand mean of D decreased as anticipated. This study highlights the functional importance of shorter, stouter tree architectures in persisting above deeper groundwater tables within and perhaps beyond riparian forests in Central Asia’s drylands. [ABSTRACT FROM AUTHOR]

Background: Metasurface coils (MCs) are a promising magnetic resonance imaging (MRI) technology. Aiming to evaluate the image quality of MCs for knee and elbow imaging, we compared signal-to-noise ratio (SNRs) obtained in standard clinical setups. Methods: Knee and elbow MRI routine sequences were applied at 1.5 T, implementing four coil scenarios: (1) 15-channel transmit/receive knee coil; (2) four-channel multipurpose coil (flex coil); (3) MC + spine coil; and (4) MC + multipurpose coil. Three regions of interest (ROIs) at different anatomical depths were compared. Results: Seven participants (aged 28 ± 2 years; 6 males) were enrolled. In elbow MRI, the MC + spine coil demonstrated the highest SNR across all ROIs (superficial-anterior: +114%, p = 0.008; middle: +147%, p = 0.008; deep-posterior: +24%, p = 0.039) compared to the flex coil and all ROIs, except the deepest from the MC, compared to the knee coil (superficial-anterior: +28%, p = 0.016; middle: +104%, p = 0.008; deep-posterior: −1%, p = 0.531). In knee MRI, the MC + spine coil provided higher SNR compared to the flex coil, except posterior (superficial-anterior: +69%, p = 0.008; middle: +288%, p = 0.008; deep-posterior: −12%, p = 0.148) versus the knee coil, the MC + spine coil was superior in the middle but non-different in superficial pre-patellar areas and less in deep-posterior areas (superficial-anterior: −8%, p = 0.188; middle: +44%, p = 0.008; deep-posterior: −36%, p = 0.016). Conclusion: Wireless MCs exhibited great potential for knee and elbow MRI outperforming the flex coil. Future developments will improve the posterior illumination to increase its clinical value. Relevance statement: MCs offer enhanced versatility, flexibility, and patient comfort. If universal MC designs can achieve image quality comparable to those of standard coils and simultaneously be utilized across multiple body areas, the technology may revolutionize future musculoskeletal MRIs. Key Points: MCs are promising in MRI, but homogeneity is challenging depending on the design. Signal-to-noise-ratio was improved for knee and elbow imaging with slight inhomogeneous illumination. MCs could match the image quality of standard coils in both knee and elbow imaging. [ABSTRACT FROM AUTHOR]

Optimizing athletic training programs with the support of predictive models is an active research topic, fuelled by a consistent data collection. The Fitness-Fatigue Model (FFM) is a pioneer for modelling responses to training on performance based on training load exclusively. It has been subject to several extensions and its methodology has been questioned. In this article, we leveraged a Bayesian framework involving biologically meaningful priors to diagnose the fit and predictive ability of the FFM. We used cross-validation to draw a clear distinction between goodness-of-fit and predictive ability. The FFM showed major statistical flaws. On the one hand, the model was ill-conditioned, and we illustrated the poor identifiability of fitness and fatigue parameters using Markov chains in the Bayesian framework. On the other hand, the model exhibited an overfitting pattern, as adding the fatigue-related parameters did not significantly improve the model's predictive ability (p-value > 0.40). We confirmed these results with 2 independent datasets. Both results question the relevance of the fatigue part of the model formulation, hence the biological relevance of the fatigue component of the FFM. Modelling sport performance through biologically meaningful and interpretable models remains a statistical challenge. [ABSTRACT FROM AUTHOR]