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Abstract A derivative is a financial asset whose future payoff is a function of underlying assets. Pricing a financial derivative involves setting up a market model, finding a martingale (“fair game”) probability measure for the model from the existing asset prices, and using that probability measure to price the derivative. When the number of underlying assets and/or the number of market outcomes in the model is large, pricing can be computationally demanding. In this work, we first formulate the pricing problem in a linear algebra setting, including the realistic setting of incomplete markets where derivatives do not have a unique price. We show that the problem can be solved with a variety of quantum techniques such as quantum linear programming and the quantum linear systems algorithm. While in previous works the martingale measure is assumed to be given, here it is extracted from market variables akin to bootstrapping, a common practice among financial institutions. We discuss the quantum zero-sum game algorithm and the quantum simplex algorithm as viable subroutines. For quantum linear systems solvers, we formalize a new market assumption milder than market completeness, which allows the potential for large speedups. Towards prototype use cases, we conduct numerical experiments motivated by the Black–Scholes–Merton model.

Abstract In many intact African savannah ecosystems, martial eagles are the top avian predator, while lions are the top terrestrial predator. Here, we report seven records of martial eagle predation or attempted predation of lion cubs in the greater Mara region, Kenya. These events resulted in the death of nine lion cubs, most of which were at least partially consumed, and are the first detailed records of this behaviour to be published. While these observations represent intraguild interactions, we suggest that they reflect neither intraguild predation nor interspecific killing. Rather, the ecology of both species coupled with the details of our records suggest that martial eagles opportunistically kill lion cubs purely to eat them. We hope that by publishing these records we will encourage others to share their observations of raptors predating on large mammalian carnivores, thus improving our understanding of a behaviour that we suspect may be more widespread than the current lack of evidence suggests.

BackgroundAlthough several digital health interventions (DHIs) have shown promise in the care of skin diseases their uptake in Germany has been limited. To fully understand the reasons for the low uptake, an in-depth analysis of patients’ and health care providers’ barriers and facilitators in dermatology is needed. ObjectiveThe objective of this study was to explore and compare attitudes, acceptability, barriers, and facilitators of patients, dermatologists, and nurses toward DHIs in dermatology. MethodsWe conducted 6 web-based focus groups each with patients (n=34), dermatologists (n=30), and nurses (n=30) using a semistructured interview guide with short descriptions of DHIs described in the literature. A content analysis was performed using deductive constructs, following the unified theory of acceptance and use of technology framework, and inductive categories. ResultsPatients identified many positive performance expectancies, such as reduced travel times and improvement in follow-up appointments. Dermatologists also stated positive effects (eg, promotion of standardized care), but also negative implications of health care digitalization (eg, increased workload). All stakeholders reported that a DHI should bring additional value to all stakeholders. A lack of digital competence among patients was identified as the major barrier to adoption by all 3 groups. Nurses and dermatologists want apps that are easy to use and easy to implement into their daily routines. Trust in selected institutions, colleagues, and physicians was identified as a facilitator. Patients reported their dependence on the dermatologists’ acceptance. All groups expressed concerns about data privacy risks and dermatologists stated insecurities toward data privacy laws. ConclusionsTo ensure successful digitalization in dermatology, apps should be user-friendly, adapted to users’ skill levels, and beneficial for all stakeholders. The incorporation of dermatologists’ perspectives is especially important as their acceptance may impact use among patients and nurses. DHIs should ensure and be transparent about data privacy. The found barriers and facilitators can be used for implementation strategies.

Background: Patients with bone metastases from solid tumors often have additional treatment with bone targeted agents (BTAs) to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture leading toradiation therapy or surgery to the bone, spinal cord compression, or hypercalcemia. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown. Methods: Patients with bone metastases treated with immunotherapy within the Alpine Tumor Immunology Registry were compared based on whether they received an additional BTA such as denosumab or zoledronic acid. The primary endpoint was time to first SSE. Continuous data were summarized as median and range, categorical data using frequency counts and percentages. Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables. Results: One hundred and ninety-seven patients with bone metastases and treatment with immunotherapy such as nivolumab (48 %), pembrolizumab (40 %), atezolizumab (12 %), ipilimumab (9 %) and other immunotherapy (5 %) were included. The most frequent tumor types were lung cancer (50 %), malignant melanoma (11 %), renal cell cancer (10 %) and bladder cancer (9 %), respectively. One hundred and twenty-two patients (62 %) received a BTA treatment (91 % denosumab). The median treatment duration of a BTA was 178 days (min: 1 day, max: 2010 days). Out of the 197 patients, 47 (24 %) experienced at least one SSE, 100 (51 %) had bone pain. Ten of the 122 patients (8 %) receiving a BTA developed osteonecrosis of the jaw (ONJ). The percentage of patients without an SSE at fixed time points was higher if treated with a BTA (e.g., at 6 months, 92 % [95 % CI: 84 % - 96 %] versus 88 % [95 % CI: 77 % - 94 %]), but no significant difference in time to first SSE (HR 0.69; 95 % CI 0.34–1.39, log-rank p = 0.29) or time to first bone pain (HR: 0.85; 95 % CI: 0.51–1.43, p = 0.54) between these two groups could be detected. There were differences in OS between patients treated with a BTA and patients not treated with a BTA (HR: 1.46; 95 % CI: 1.01–2.10, p = 0.043). Conclusion: No significant difference in time to first SSE or bone pain was observed between patients who have received a BTA or not when treated with immunotherapy. Based on these retrospective results the indication of BTAs to reduce SSEs in cancer patients under treatment with immunotherapy needs further evaluation.

Objective: This video aims to provide a detailed description of a robot-assisted laparoscopic harvest of a vertical rectus abdominis muscle (VRAM) for interposition in a complex vesicovaginal fistula repair. Patient: The case presented involves a 38-year-old female patient with a body mass index of 54, who was undergoing chemotherapy for stage 3 high-grade endometrial carcinoma. The patient experienced recurrent urinary tract infections and continuous leakage of fluid per vagina one month after undergoing a robot-assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and macrodebulking. Cystoscopy revealed a 3 cm vesicovaginal fistula, which was biopsied and found to exhibit necrosis and dystrophic calcification. Surgical procedure: Considering the size of the fistula, interposition tissue was deemed necessary for the repair. The patient had previously undergone omentectomy, and macrobulking of the peritoneum was performed by the gyn-oncologists. Consequently, the VRAM was identified as the most suitable option. The vesicovaginal fistula repair was conducted using standard pelvic port placement. 3–0 PDS stay sutures were placed between and around the bladder and vaginal closures to secure the VRAM in place. The robot was undocked and re-docked to a retroperitoneal configuration, and with the aid of a 30 up camera, the posterior rectus sheath was opened. The muscle was dissected off the anterior sheath, with any perforating vessels being ligated and the superior epigastric artery being sealed using a vessel sealer. The flap was then rotated into the pelvis and secured over the bladder and vaginal defect closure. The inferior epigastric artery supplies the flap. With the robotic approach the anterior sheath remains intact. The posterior sheath is not closed. This can cause a post-operative budge in the area. Results: The patient was discharged with an 18 Fr foley catheter, and a postoperative cystogram was performed at 3 weeks, revealing no evidence of a leak. The patient has been followed for 15 months without reporting any urological complaints. Conclusion: The VRAM represents a robust and healthy flap that can be safely harvested using robotic techniques. It can be effectively employed in pelvic reconstruction to fill dead space or serve as tissue interposition

Abstract Lack of rigorous reproducibility and validation are significant hurdles for scientific development across many fields. Materials science, in particular, encompasses a variety of experimental and theoretical approaches that require careful benchmarking. Leaderboard efforts have been developed previously to mitigate these issues. However, a comprehensive comparison and benchmarking on an integrated platform with multiple data modalities with perfect and defect materials data is still lacking. This work introduces JARVIS-Leaderboard, an open-source and community-driven platform that facilitates benchmarking and enhances reproducibility. The platform allows users to set up benchmarks with custom tasks and enables contributions in the form of dataset, code, and meta-data submissions. We cover the following materials design categories: Artificial Intelligence (AI), Electronic Structure (ES), Force-fields (FF), Quantum Computation (QC), and Experiments (EXP). For AI, we cover several types of input data, including atomic structures, atomistic images, spectra, and text. For ES, we consider multiple ES approaches, software packages, pseudopotentials, materials, and properties, comparing results to experiment. For FF, we compare multiple approaches for material property predictions. For QC, we benchmark Hamiltonian simulations using various quantum algorithms and circuits. Finally, for experiments, we use the inter-laboratory approach to establish benchmarks. There are 1281 contributions to 274 benchmarks using 152 methods with more than 8 million data points, and the leaderboard is continuously expanding. The JARVIS-Leaderboard is available at the website: https://pages.nist.gov/jarvis_leaderboard/

Abstract Background Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0–5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. Results Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the “lame” trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the “sound” trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. Conclusions When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Abstract Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention. Strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech. Combining simultaneously recorded eye tracking and magnetoencephalographic data with temporal response functions, we show that gaze tracks attended speech, a phenomenon we termed ocular speech tracking. Ocular speech tracking even differentiates a target from a distractor in a multi-speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition.

In this study, we explored the effects of chronic stress on lumpfish (Cyclopterus lumpus) physiological, immune response, health, and plasma free amino acids. 3 groups of lumpfish were exposed to 1-minute air exposure. 1 group was exposed to stress once per week, a second group exposed 2 times per week, and a third group exposed 4 times per week. The present study revealed significant alterations in immunity and increased nutritional demands, particularly the branched chain amino acids and lysine. Cortisol levels fluctuated, with significantly higher levels halfway through the experiment on the groups that were stressed more often. Though, by the end of the experiment, there were no significant differences in cortisol levels between groups. Regardless of stress exposure, cataract developed in virtually all sampled fish, pointing toward a potential dietary imbalance. A transient immunomodulation of stress was visible. While in early stages stress had an immune enhancing effect, as seen by the increase in plasma nitric oxide and peroxidase in the group most frequently exposed to stress, these differences were not apparent by the end of the experiment. Additionally, the worst health condition was found in this group. Our results underscore the complex interplay between stress, immunity and nutrition, highlighting the need for tailored dietary strategies and improved rearing practices.

Background: Invasive Staphylococcus aureus infections cause significant morbidity and mortality in neonatal intensive care unit (NICU) infants.1 Colonization (asymptomatic carriage in the nose, skin, or gut) is a risk factor for subsequent invasive infection (e.g., pneumonia, bone infections, bloodstream infections, etc.). Active surveillance and decolonization measures for S. aureus-colonized infants have been associated with decreased invasive infection rates. 2-4 Methods: A methicillin-resistant S. aureus (MRSA) surveillance and decolonization program, consisting of admission and weekly MRSA nasal cultures followed by intranasal mupirocin plus chlorhexidine baths for colonized infants, was implemented in our level IV NICU with 150 beds in 2006.5 Due to poor compliance with decolonization protocols5, existing practices were reviewed and multiple interventions to increase compliance were implemented in 2018. These renewed efforts included revision of the existing MRSA decolonization protocol, updating the associated electronic medical record order set, re-education of unit staff, and weekly review by the Infection Prevention (IP) and NICU leadership teams to ensure the decolonization protocol was followed for newly colonized infants. Mean MRSA bloodstream infection (BSI) rates were calculated quarterly pre- (January 2014-December 2017) and post- (January 2018-December 2023) implementation of renewed efforts and compared via unpaired t-test. In July 2020 a similar methicillin-susceptible S. aureus (MSSA) surveillance and decolonization program was implemented with an associated revision of existing documents, education campaign, and weekly review of infants with new MSSA colonization. Mean MSSA BSI rates pre- (July 2018-June 2020) and post- (July 2020-December 2023) implementation were compared via unpaired t-test. Results: Renewed implementation of MRSA surveillance and decolonization was associated with a sustained decrease in the mean MRSA BSI rate (Figure 1): 0.10 per 1000 patient-days pre-implementation, 0.03 post-implementation (p=0.02). Following implementation of MSSA surveillance and decolonization, there was no statistically significant change in the mean MSSA BSI rate (Figure 2): 0.20 per 1000 patient-days pre-implementation, 0.15 post-implementation (p=0.32). Conclusions: Implementation of a robust MRSA surveillance and decolonization program in the NICU was associated with a sustained decrease in invasive MRSA infections. No change in invasive MSSA infection rates was observed following implementation of a similar protocol for MSSA. Additional research is needed to better understand the role of MSSA surveillance and decolonization in the NICU.

Abstract Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells. In longitudinally studied bone marrow cells from a patient at FPD-MM vs RUNX1-FPD state, we confirmed increased chromatin accessibility and mRNA expressions of MYB, MECOM and BCL2 in FPD-MM cells. GMR-AML1 and PD FPD-MM cells were sensitive to homoharringtonine (HHT or omacetaxine) or mebendazole-induced lethality, associated with repression of c-Myc, EVI1, PLK1, CDK6 and MCL1. Co-treatment with MB and the PLK1 inhibitor volasertib exerted synergistic in vitro lethality in GMR-AML1 cells. In luciferase-expressing GMR-AML1 xenograft model, MB, omacetaxine or volasertib monotherapy, or co-treatment with MB and volasertib, significantly reduced AML burden and improved survival in the immune-depleted mice. These findings highlight the molecular features of FPD-MM progression and demonstrate HHT, MB and/or volasertib as effective agents against cellular models of FPD-MM.

Abstract Background The revision knee complexity classification (RKCC) stratifies knee revision operations depending on their level of complexity from simple revisions (R1) to highly complex cases (R3). Current financial codes used for calculation of reimbursement for knee revision services provided at the Trust, rely on patients’ comorbidities. However, previous research has demonstrated that this approach may not yield an accurate financial account of knee revision arthroplasty cost. This is a single centre study from a secondary and tertiary revision unit, with work previously presented by the authors demonstrating that the majority of complex revision knee replacement within the region, take place in this unit. The aims of this study were to illustrate the current cost profile and renumeration service currently in place for revision knee and show the differences in cost based on complexity of the operation. Methods In this retrospective study, 90 cases who underwent revision knee operations in 2019 were analysed. Data was obtained from a tertiary referral centre where the episodes had occurred. Mean cost, tariff, and subsequent deficit were calculated for the R1, R2 and R3 episodes. Results R2 and R3 episodes were significantly more expensive than R1 episodes. The increase in cost between R3 and R2 episodes was not significant. The total cost of the revision operations was £1,162,343. Tariffs received for R2 and R3 revision operations were significantly more expensive than R1 operations. However, the increase in tariffs received for R3 operations was not significant in relation to R2 operations. The total amount of tariffs received by the Trust was £ 770,996 generating a net deficit of - £ 391,347. Conclusion Current financial coding for revision knee does not accurately predict costs associated with revision knee surgery. Net deficit varies depending on the RKCC grade of the knee revision episode with more complex operations resulting in a higher mean net deficit. Implementation of the RKCC could prove to be a useful tool in generating an accurate prediction of the cost associated with knee revision surgery.

In recent years, Quantum Machine Learning (QML) has increasingly captured the interest of researchers. Among the components in this domain, activation functions hold a fundamental and indispensable role. Our research focuses on the development of activation functions quantum circuits for integration into fault-tolerant quantum computing architectures, with an emphasis on minimizing T-depth. Specifically, we present novel implementations of ReLU and leaky ReLU activation functions, achieving constant T-depths of 4 and 8, respectively. Leveraging quantum lookup tables, we extend our exploration to other activation functions such as the sigmoid. This approach enables us to customize precision and T-depth by adjusting the number of qubits, making our results more adaptable to various application scenarios. This study represents a significant advancement towards enhancing the practicality and application of quantum machine learning.

What are the effects of cycling infrastructure? This question is crucial as cities begin to give more space to cycling. In this paper, we propose to use the theoretical concept of affordance to consider not only what a cycle lane affords (or enables), but also how it does this and for whom. This has led us to consider three dimensions: (1) the number of cyclists using a route, (2) their characteristics and (3) their experience of cycling. We adopt an approach that combines counting, observation, and intercept surveys both before and then one year after the installation of a new 1.1 km cycle lane in Fribourg, Switzerland. A large increase in cycling traffic following the introduction of the cycle lane (+20 % on weekdays) reveals a latent demand that has been triggered by an improvement in cycling infrastructure. While the characteristics of cyclists (age, gender, etc.) did not fundamentally change, there was a clear improvement in the experience of cycling, particularly in terms of feeling safe. This effect is important, as developing cycling is not only about attracting new users but also reinforcing potentially fragile existing practices. Nonetheless, for a minority of users, the new infrastructure still does not meet safety expectations, and the lack of cycling amenities in the rest of the town limits the expansion of cycling. The approach we have designed could be replicated in other contexts by researchers, advocates, or professionals in order to obtain comparative data on cycling infrastructure.

IntroductionRecent research on word learning has found that adults can rapidly learn novel words by tracking cross-situational statistics, but learning is greatly influenced by the phonological properties of the words and by the native language of the speakers. Mandarin-native speakers could easily pick up novel words with Mandarin tones after a short exposure, but English-native speakers had specific difficulty with the tonal components. It is, however, unclear how much experience with Mandarin is needed to successfully use the tonal cue in word learning. In this study, we explored this question by focusing on the heritage language population, who typically are exposed to the target language at an early age but then develop and switch to another majority language. Specifically, we investigated whether heritage Mandarin speakers residing in an English-speaking region and speaking English as a dominant language would be able to learn novel Mandarin tonal words from statistical tracking. It helps us understand whether early exposure to the target feature is sufficient to promote the use of that feature in word learning later in life.MethodsWe trained 30 heritage Mandarin speakers with Mandarin pseudowords via a cross-situational statistical word learning task (CSWL).Results and discussionHeritage Mandarin speakers were able to learn the pseudowords across multiple situations, but similar-sounding words (i.e., minimal pairs) were more difficult to identify, and words that contrast only in lexical tones (i.e., Mandarin lexical tone) were distinguished at chance level throughout learning. We also collected information about the participants’ heritage language (HL) experience and usage. We did not observe a relationship between HL experience/usage and performance in tonal word learning, suggesting that HL exposure does not necessarily lead to an advantage in learning the target language.

Abstract Understanding fish movement is critical in determining the spatial scales in which to appropriately manage wild populations. Genetic markers provide a natural tagging approach to assess the degree of gene flow and population connectivity across a species distribution. We investigated the genetic structure of black bream Acanthopagrus butcheri across its entire distribution range in Australia, as well as regional scale gene flow across south‐eastern Australia by undertaking a comprehensive analysis of the populations in estuaries across the region. We applied genome‐wide sampling of single‐nucleotide polymorphism (SNP) markers generated from restriction site‐associated DNA sequencing. Genetic structure and potential gene flow was assessed using principal component analyses and admixture analyses (STRUCTURE). Using 33,493 SNPs, we detected broad scale genetic structuring, with limited gene flow among regional clusters (i.e. Western Australia, South Australia and western Victoria; and eastern Victoria, Tasmania and New South Wales). This is likely the result of unsuitable habitats, strong ocean currents (e.g. the Leeuwin Current and the East Australian Current), large water bodies (e.g. Bass Strait) and known biogeographical provinces across the continent. Local‐scale genetic structuring was also identified across the south‐eastern Australian estuaries sampled, reflecting that the coexistence of both migratory and resident individuals within populations (i.e. partial migration), and the movement of fish into coastal waters, still results in strong philopatry across the region. Instances of movement among estuaries at this spatial scale were primarily found between adjacent estuaries and were likely attributed to lone migrants utilising inshore coastal currents for movement beyond nearby habitats. Targeting SNP markers in A. butcheri at this continental scale highlighted how neither spatial proximity of estuaries nor black bream's ability to move into coastal waters reflects increased gene flow. Overall, our findings highlight the importance of location‐specific management.

Abstract Background With sustainable bioenergy in the European energy mix, intermediate bioenergy carriers (IBC) become of growing importance, as they can ensure a more efficient utilisation of biomass feedstocks from agricultural and forest residues. A high potential for market uptake is foreseen for fast pyrolysis bio-oil (FPBO), one of several IBCs. While facing the chicken and egg problem in market entry, the aim of this study was the development of adequate strategies to support market implementation. The case study findings and methodological approach can provide policymakers, industry, and a broader audience with a vision for addressing similar challenges in market adoption of innovations in the bioeconomy and beyond. Therefore, we tested a new PESTEL + I approach and its practical applicability to an IBC value chain. Results With an adopted PESTEL method, we analysed a promising value chain in which FPBO is produced from sawdust in Sweden and Finland, transported to the Netherlands and upgraded and marketed as a marine biofuel. Our results show that the market uptake of IBCs such as FPBO and subsequently produced biofuels is above all driven by the European Renewable Energy Directive II (RED II). In Annex IX Part A, sawdust is listed as a feedstock for advanced biofuels, which can be double counted towards the 14% renewable energy share goal in the transport sector in 2030. To support the use of advanced biofuels in the maritime and aviation sector, the proposal for revision of RED II 2021 contains a new multiplier (1.2x) for fuels delivered to these sectors, while all other multipliers are deleted. These legal European obligations and implementation into national law of member states create strong incentives for many downstream market actors to use advanced biofuel. However, technological challenges for FPBO use still hamper fast market introduction. Conclusions Overcoming technology challenges and the creation of long-term validity of guidelines and regulatory framework will create stable market conditions, investment security and finally stimulate long-term offtake agreements between feedstock providers, technology developers and downstream customers. The approach and findings can provide a vision to overcome similar challenges in other bioeconomy innovations’ market uptake and beyond.

Abstract HOMO and LUMO energies are critical molecular properties that typically require high accuracy computations for practical applicability. Until now, a comprehensive dataset containing sufficiently accurate HOMO and LUMO energies has been unavailable. In this study, we introduce a new dataset of HOMO/LUMO energies for QM9 compounds, calculated using the GW method. The GW method offers adequate HOMO/LUMO prediction accuracy for diverse applications, exhibiting mean unsigned errors of 100 meV in the GW100 benchmark dataset. This database may serve as a benchmark of HOMO/LUMO prediction, delta-learning, and transfer learning, particularly for larger molecules where GW is the most accurate but still numerically feasible method. We anticipate that this dataset will enable the development of more accurate machine learning models for predicting molecular properties.

Objectives: Despite the currently prevailing, milder Omicron variant, coronary artery disease (CAD) patients constitute a major risk group in COVID-19, exhibiting 2.6 times the mortality risk of non-CAD patients and representing over 22% of non-survivors. No data are currently available on the efficacy of antibody levels in CAD patients, nor on the relevance of vaccination status versus antibody levels for predicting severe courses and COVID-19 mortality. Nor are there definitive indicators to assess if individual CAD patients are sufficiently protected from adverse outcomes or to determine the necessity of booster vaccinations. Methods: A prospective, propensity-score-matched, multicenter cohort study comprising 249 CAD patients and 903 controls was conducted. Anti-SARS-CoV-2-spike antibodies were measured on hospital admission. Prespecified endpoints were in-hospital mortality, intensive care, and oxygen administration. Results: After adjustment for potential confounders, CAD patients exhibited 4.6 and 6.1-times higher mortality risks if antibody levels were p < 0.001; 6.147, 95%CI 2.529–14.941, p < 0.001). Risk of intensive care was 3.7 and 4.0 (p = 0.003; p < 0.001), and risk of oxygen administration 2.6 and 2.4 times higher below these thresholds (p = 0.004; p = 0.010). Vaccination status was a weaker predictor of all three outcomes than both antibody thresholds. Conclusion: Antibody levels are a stronger predictor of outcome in CAD patients with COVID-19 than vaccination status, with 1200 BAU/mL being the more conservative threshold. Measuring anti-SARS-CoV-2 antibodies in CAD patients may ensure enhanced protection by providing timely booster vaccinations and identifying high-risk CAD patients at hospital admission.

Hoof care providers are pivotal for implementing biomechanical optimizations of the musculoskeletal system in the horse. Regular visits allow for the collection of longitudinal, quantitative information (“normal ranges”). Changes in movement symmetry, e.g., after shoeing, are indicative of alterations in weight-bearing and push-off force production. Ten Warmblood show jumping horses (7–13 years; 7 geldings, 3 mares) underwent forelimb re-shoeing with rolled rocker shoes, one limb at a time (“limb-by-limb”). Movement symmetry was measured with inertial sensors attached to the head, withers, and pelvis during straight-line trot and lunging. Normalized differences pre/post re-shoeing were compared to published test–retest repeatability values. Mixed-model analysis with random factors horse and limb within horse and fixed factors surface and exercise direction evaluated movement symmetry changes (p < 0.05, Bonferroni correction). Withers movement indicated increased forelimb push-off with the re-shod limb on the inside of the circle and reduced weight-bearing with the re-shod limb and the ipsilateral hind limb on hard ground compared to soft ground. Movement symmetry measurements indicate that a rolled rocker shoe allows for increased push-off on soft ground in trot in a circle. Similar studies should study different types of shoes for improved practically relevant knowledge about shoeing mechanics, working towards evidence-based preventative shoeing.

BackgroundIn recent years, legal and infrastructural conditions have been set to improve the adoption of digital applications in health care in Germany. The impact of these actions was amplified by the COVID-19 pandemic. So far, no studies have confirmed this progress in dermatology. ObjectiveThe aim of this study was to measure changes in knowledge, interest, expectation, and use of digital applications in health care among dermatologists in Germany in 2019 and 2021. MethodsWe administered a repeated cross-sectional survey among dermatologists in medical practices and clinics in Germany at 2 time points: t1 (2019; before the COVID-19 pandemic) and t2 (2021; during the COVID-19 pandemic). We used a standardized questionnaire, including items on respondents’ knowledge, interest, expectation, and use of digital applications, as well as their demographics. The survey was distributed by post and email. The data were analyzed descriptively as well as with multiple logistic regressions. ResultsAt t1, 585 (272/571, 47.6% female; mean age 52.4, SD 8.9 years) dermatologists and at t2, 792 (360/736, 48.9% female; mean age 54.3, SD 8.6 years) dermatologists participated in this survey. Interest in digital medicine was higher at t1 than at t2 (381/585, 65.1% vs 458/792, 57.8%; P≤.001). Nevertheless, 38.6% (306/792) had used digital applications more often since the beginning of the pandemic. For example, real-time telemedicine with patients (12/585, 2.1% vs 160/792, 7.6%; P≤.001) and other specialists did increase (33/385, 5.7% vs 181/792, 22.8%; P≤.001). Almost one-third expressed great concerns about digitalization (272/792, 34.3% vs 294/792, 37.1%; P=.21). Spatial analysis revealed higher interest in, more positive expectations toward, and higher use of digital applications in urban areas in comparison to rural areas. For instance, dermatologists from urban areas assessed future applications as having less risk (adjusted odds ratio [aOR] 0.51, 95% CI 0.35-0.76) than did dermatologists from rural areas. The situation was similar with the age groups, as, for example, dermatologists aged

Causal machine learning tools are beginning to see use in real-world policy evaluation tasks to flexibly estimate treatment effects. One issue with these methods is that the machine learning models used are generally black boxes, that is, there is no globally interpretable way to understand how a model makes estimates. This is a clear problem for governments who want to evaluate policy as it is difficult to understand whether such models are functioning in ways that are fair, based on the correct interpretation of evidence and transparent enough to allow for accountability if things go wrong. However, there has been little discussion of transparency problems in the causal machine learning literature and how these might be overcome. This article explores why transparency issues are a problem for causal machine learning in public policy evaluation applications and considers ways these problems might be addressed through explainable AI tools and by simplifying models in line with interpretable AI principles. It then applies these ideas to a case study using a causal forest model to estimate conditional average treatment effects for returns on education study. It shows that existing tools for understanding black-box predictive models are not as well suited to causal machine learning and that simplifying the model to make it interpretable leads to an unacceptable increase in error (in this application). It concludes that new tools are needed to properly understand causal machine learning models and the algorithms that fit them.

It was recently reported that values of the transition heat capacities, as measured by differential scanning calorimetry, for two globular proteins and a short DNA hairpin in NaCl buffer are essentially equivalent, at equal concentrations (mg/mL). To validate the broad applicability of this phenomenon, additional evidence for this equivalence is presented that reveals it does not depend on DNA sequence, buffer salt, or transition temperature (Tm). Based on the equivalence of transition heat capacities, a calorimetric method was devised to determine protein concentrations in pure and complex solutions. The scheme uses direct comparisons between the thermodynamic stability of a short DNA hairpin standard of known concentration, and thermodynamic stability of protein solutions of unknown concentrations. Sequences of two DNA hairpins were designed to confer a near 20°C difference in their Tm values. In all cases, evaluated protein concentrations determined from the DNA standard curves agreed with the UV-Vis concentration for monomeric proteins. For multimeric proteins evaluated concentrations were greater than determined by UV-Vis suggesting the calorimetric approach can also be an indicator of molecular stoichiometry.

Introduction Currently, no group specifically supports and coordinates primary care focused cancer research in Ireland. The aim of this project is to establish an inclusive stakeholder group for primary care focused cancer research in Ireland, to coordinate research efforts and build capacity in researchers and institutions. Methods We will convene a stakeholder group, recruiting individuals with personal and professional experience of cancer care in a community setting. “Core stakeholders”—patients, clinicians, researchers, and policymakers—will attend regularly. Additional “specialist stakeholders”, such as representatives of secondary care, private healthcare, health insurance, industry, cancer charities, and health research funders, will participate on an ad hoc basis. An e-Delphi consensus process will be used to assess the stakeholders’ views on: (1) the relevance and importance of primary care focused cancer research; (2) the potential role and scope of the stakeholder group; (3) how best to engage with lived experience stakeholders and healthcare professionals affected by the research; (4) how to encourage the dissemination of results and the translation of findings into practice. Round 1 will be open-ended and will invite the independent suggestions of stakeholders; in Round 2 and 3, group members will vote on the inclusion of these suggestions in a position statement by the group, with consensus defined as ≥75% agreement. Discussion The formation of a broad stakeholder group to support primary care focused cancer research will ensure research is relevant, patient centered, and more readily translated into practice. It is also hoped that the group will support capacity building and strategic planning in this important research space.

Background C reactive protein (CRP) kinetics have recently been suggested as predictive biomarkers for the efficacy of immune checkpoint inhibitor (ICI) therapy in selected cancer types. The aim of this study was to characterize early CRP kinetics as a tumor-agnostic biomarker for ICI treatment outcomes.Methods In this multicenter retrospective cohort study, two independent cohorts of patients with various cancer types undergoing palliative ICI treatment at Austrian academic centers served as the discovery (n=562) and validation cohort (n=474). Four different patterns of CRP kinetics in the first 3 months of ICI therapy were defined (CRP-flare responders, CRP-responders, CRP non-responders, patients with all-normal CRP). Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were defined as coprimary endpoints. Univariable and multivariable logistic regression, landmark analysis and Cox regression including CRP kinetics as time-dependent variable were performed.Results The ORR in patients with all-normal CRP, CRP responders, CRP flare-responders and CRP non-responders was 41%, 38%, 31% and 12%, respectively. The median OS and PFS estimates were 24.5 months (95% CI 18.5 to not reached) and 8.2 months (95% CI 5.9 to 12.0) in patients with all-normal CRP, 16.1 months (95% CI 12.6 to 19-8) and 6.1 months (95% CI 4.9 to 7.2) in CRP-responders, 14.0 months (95% CI 8.5 to 19.4) and 5.7 months (95% CI 4.1 to 8.5) in CRP flare-responders and 8.1 months (95% CI 5.8 to 9.9) and 2.3 months (95% CI 2.2 to 2.8) in CRP non-responders (log-rank p for PFS and OS

Abstract Background We evaluated the hydrostatic pressure of the renal pelvis (RPP) as a radiation-free alternative to fluoroscopic nephrostogram to assess ureteral patency after percutaneous nephrolithotomy (PCNL). Methods Retrospective non-inferiority study analyzing 248 PCNL-patients (86 female (35%) and 162 males (65%)) between 2007 and 2015. Postoperatively, RPP was measured using a central venous pressure manometer in cmH2O. The primary endpoint was to assess RPP depending on the patency of the ureter and the nephrostomy tube removal. Secondary, the upper limit of normal RPP of $$\le$$ ≤ 20 cmH2O was assessed as an indicator of an unobstructed patency. Results The median procedure duration was 141 min (112–171.5) with a stone free rate of 82% (n = 202). RPP was significantly higher in patients with obstructive nephrostogram with 25.0 mmH2O (21.0–32.0) versus 20.0 mmH2O (16.0–24.0; p

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

ABSTRACT Purpose: The primary objective of this study was to compare the WALANT (wide awake, local anesthesia, no tourniquet) technique with local anesthesia associated with sedation in relation to pain intensity for minor hand surgical procedures. The secondary objective was to evaluate the need for analgesic complementation. Methods: A prospective, randomized, comparative, and clinical study was carried out. The sample size in each group was determined after statistical evaluation of the results of a pilot project. The participants were allocated to one of two groups; those in group 1 were submitted to the WALANT technique, and those in group 2, to local anesthesia associated with sedation, for elective surgery. The surgical procedures were carpal tunnel syndrome, De Quervain’s tenosynovitis, synovial cyst, finger cyst, and trigger finger. Pain intensity, need for complementation and evolution to complex regional pain syndrome were evaluated. Results: There was no difference between groups in pain intensity after WALANT and need for intraoperative complementation. There was no significant difference in the amount of opioid applied postoperatively between the groups. There was no difference between groups regarding comfort during surgery. There was no difference in adverse effects and complications between the groups. Hematoma was the most frequent adverse event. No severe adverse events were observed. Conclusions: The WALANT technique promoted an analgesic effect similar to that of local anesthesia associated with sedation, without increasing adverse effects.

Depuis quelques années, Naval Group s'approprie la technologie de Focalisation en Tous Points (FTP plus connue sous son acronyme anglais TFM) en l'appliquant progressivement à ses cas industriels. Deux applications sont présentées dans cet article : – une utilisation de la TFM pour les mesures de profilométrie interne de composants, – une utilisation de la TFM pour le contrôle d'une soudure de forte épaisseur. Pour chaque cas, l'application est décrite et les comparaisons entre différentes techniques ultrasonores sont effectuées. Une analyse des gains potentiels est présentée. Des explications physiques utilisant la simulation CIVA sont proposées. Les éventuels inconvénients sont aussi discutés.

Dans le cadre de ses contrats, NAVAL GROUP assure le Maintien en Conditions Opérationnelles des sous-marins et bâtiments de surfaces de la Marine Nationale. Les contrôles non destructifs par ressuage, largement mis en oeuvre, participent à démontrer l’intégrité de matériaux métalliques sur coque et structure de ces bâtiments. Néanmoins, ces méthodes nécessitent des précautions particulières afin de limiter leur impact sur l’environnement et la santé des opérateurs (traitement des déchets, port de masques…) et de surcroît présentent de réelles contraintes en termes de mises en oeuvre à bord des bâtiments en phase de maintenance notamment. A ce titre, plusieurs études sur l’utilisation de capteurs courants de Foucault multiéléments sont menées au sein du département END du CESMAN (Centre d’Expertise des Matériaux et Structures Navales) sur diverses applications avec pour but de se substituer aux méthodes de ressuage. Un état des lieux de ces différentes études est présenté.

Depuis quelques années, Naval Group s’approprie la technologie Focalisation en Tous Points (FTP plus connue sous son acronyme anglais TFM) en l’appliquant progressivement sur des cas industriels concrets. Ce papier présente un premier retour d’expérience de la qualification formelle de la technologie TFM appliquée à l’inspection en service des chaufferies nucléaires embarquées de la propulsion navale. L’application présentée ici utilise la technologie TFM en mode émission/réception séparée sur des soudures de composant nucléaire en acier austénitique ou ferritique de forte épaisseur. Ces applications font l’objet d’une qualification conventionnelle au sens du référentiel interne actuellement en cours d’instruction. La configuration est brièvement présentée : elle utilise des traducteurs positionnés en mode Pitch Catch. La liste des paramètres influents est présentée et quelques résultats tirés des dossiers de justifications techniques utilisant assez largement la simulation mais aussi les expériences sont discutées. Certaines spécificités de la TFM en termes de qualifications sont soulignées. Les avantages/inconvénients de la technique sont évoquées et lorsque c’est possible, quantifiées.

The haem enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the rate-limiting step in the kynurenine pathway of tryptophan metabolism and plays an essential role in immunity, neuronal function, and ageing. Expression of IDO1 in cancer cells results in the suppression of an immune response, and therefore IDO1 inhibitors have been developed for use in anti-cancer immunotherapy. Here, we report an extension of our previously described highly efficient haem-binding 1,2,3-triazole and 1,2,4-triazole inhibitor series, the best compound having both enzymatic and cellular IC50 values of 34 nM. We provide enzymatic inhibition data for almost 100 new compounds and X-ray diffraction data for one compound in complex with IDO1. Structural and computational studies explain the dramatic drop in activity upon extension to pocket B, which has been observed in diverse haem-binding inhibitor scaffolds. Our data provides important insights for future IDO1 inhibitor design.

Abstract Background The preservation or restoration of hip geometry following total hip arthroplasty (THA) is of importance, considering that alterations in the centrum-collum-diaphysis (CCD)-angle, femoral offset (FO), acetabular offset (AO) and total offset (TO) change hip biomechanics. Therefore, the most suitable implant should be used. The aim of this study was to compare the ability of two short-stem-systems and one straight-stem-system to reconstruct hip geometry. Methods Two-hundred-fifty-one patients (mean age: 62.0 ± 10.0 years; 51.8% males) undergoing THA with three different stem types were retrospectively included, after excluding 11 patients with missing radiological follow-up. Pre- and postoperative radiographic images (group I, ANA.NOVA Alpha Schaft Proxy®, ImplanTec, 12 options: n = 99; group II, Optimys® Mathys, 24 options: n = 62; group III: Corail®-System, DePuy-Synthes, 76 options: n = 90) were analyzed. Differences in pre- and postoperative hip geometry (i.e. CCD, FO, AO, TO) were compared between groups with one-way-analysis-of-variance (ANOVA), and post-hoc t-tests. Results The CCD-angle increased by a mean of 8.4° ± 7.2° from pre-to postoperative, with no significant difference between groups (p = 0.097). Significantly larger increases in FO were observed for groups II (4.1 mm ± 7.8 mm) and III (4.9 ± 7.2 mm), in comparison to group I (1.6 ± 6.9 mm; p = 0.006). AO decreased by a mean of 2.2 ± 4.5 mm, with the largest decrease observed in group III (-3.3 ± 5.3 mm), and the smallest for group I (-1.4 ± 3.6 mm; p = 0.011). There was no significant difference in change of TO between groups (p = 0.177). Conclusions Reconstruction of hip geometry using a single-version novel short-stem-system is achievable with comparable results to stem-systems offering multiple options.

Graph neural networks are machine learning models that directly access the structural representation of molecules and materials. This Review discusses state-of-the-art architectures and applications of graph neural networks in materials science and chemistry, indicating a possible road-map for their further development.

The psychostimulant-sensitive neural mechanism linking the circadian clock to locomotion is unknown. Here, hypothalamic A14 neurons are shown to time diurnal activity by entraining the lateral septum, and their activity is shown to be sensitive to amphetamine.

Abstract Cementless calcar-guided femoral short stems in total hip arthroplasty (THA) have become increasingly popular over the years. Early distal migration of femoral stems measured by Einzel-Bild-Roentgen Analyse, Femoral Component Analyse (EBRA-FCA) has been reported to be a risk factor for aseptic loosening. The aim of this study was to analyse axial migration behavior and subsidence of a new short stem (launched in 2015) over a follow-up period of 3 years. According to the study protocol, 100 hip osteoarthritis patients who consecutively received an unilateral cementless calcar-guided short stem (ANA.NOVA proxy) at a single department were prospectively included in this mid-term follow-up study. Thirteen patients were lost to follow-up, resulting in 87 patients with unilateral THA who fulfilled the criteria for migration analysis with EBRA-FCA. The cohort comprised 41 males (mean age: 60 ± 16.5; mean BMI (Body Mass Index): 30 ± 13) and 46 females (mean age: 61 ± 15.5; mean BMI: 27 ± 10). Seven standardized radiographs per patient were analyzed with EBRA-FCA. An average migration of 2.0 mm (0.95–3.35) was observed within the first 3 years. The median increase during the first year was higher than in the second and third year (1.2 mm [IQR: 0.5–2.15] vs. 0.3 mm [IQR: 0.1–0.6 mm] vs. 0.25 mm [IQR: 0.1–0.5 mm]. Detected migration did not lead to stem loosening, instability, dislocation, or revision surgery in any patient. A higher risk for subsidence was observed in male and heavyweight patients, whereas the female gender was associated with a lower risk. No correlation between migration and revision could be observed. Although moderate subsidence was detectable, the performance of the short stem ANA.NOVA proxy is encouraging. Yet, its use may be re-considered in overweight and male patients due to more pronounced subsidence.

Abstract Robustness analysis can support the design and operation of large‐scale water infrastructure projects confronting deeply uncertain futures. However, diverse actors, contextual specificities, sectoral interests, and risk attitudes make it difficult to identify an appropriate robustness metric to rank decision alternatives under deep uncertainty. Here, we clarify how methodological choices affect robustness evaluation using the multi‐actor, multi‐sector Inchampalli‐Nagarjuna Sagar water transfer megaproject in Southern India. We compare a suite of water transfer strategies discovered using evolutionary multi‐objective direct policy search (EMODPS), a strategy proposed by regional authorities and the status quo of no water transfer. We stress‐test these strategies across scenarios that capture climatic and socioeconomic uncertainties and rank them using robustness metrics representing sectoral perspectives and priorities of different actors with varying risk attitudes. Results show a considerable impact of metric choices on robustness rankings of strategies, with compromise solution discovered via EMODPS as robust. The no‐transfer strategy results in the worst water supply robustness with an average volumetric deficit of 17% of total historical demands but emerges as a robust alternative for 6 out of 12 combinations of actor‐sectors with high risk aversion. Also, changes in the amplitude of the Indian Summer Monsoon is identified as the most important uncertain factor determining the failure of strategies. Our findings highlight that the selection of robust solutions should be guided by an understanding of how assumed risk attitudes shape stakeholders' perceptions of vulnerabilities. These findings are generalizable to large infrastructure projects with diverse stakeholders and multisectoral impacts.

Abstract Immobilization of oligonucleotides on solid surfaces is an important step in many experimental workflows in biology, such as gene expression analysis, genotyping, and drug discoveries. Capturing oligonucleotides in a highly efficient miniaturized format is still challenging. In this work, preparation of functionalized miniaturized acrylamide hydrogels on a droplet microarray (DMA) chip is reported. By further modification of these hydrogels through the Cu‐catalyzed alkyne‐azide cycloaddition, oligonucleotides are attached covalently, creating the OligoHydrogelArray (OHA). OHA enables the hybridization of oligonucleotides with defined sequences in a parallelized, miniaturized, and high‐throughput manner with an overall loading capacity and extraction efficiency suitable for most biological and chemical applications. This system enables the parallelized solid‐phase extraction of target oligonucleotides out of a mixture for purification and enrichment of DNA/RNA/PNA for application in fields such as transcriptomics. In the current study, are establish the chemical procedure for reproducible preparation of OHA and determine key characteristics, such as height, diameter, and shape of miniaturized gel pads as well as the loading capacity of oligonucleotides within the material. Finally, the ability to extract complementary oligonucleotide strands out of solution through hybridization is demonstrated to set the course for future applications.

Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden’s J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated.

The Peregrine Ion Trap Mass Spectrometer (PITMS) is a mass spectrometer instrument that operated during the Astrobotic Peregrine Mission-1 as part of the NASA Commercial Lunar Payload Services initiative. This paper describes the instrument and investigation design, development, and planning conducted by the PITMS team, consisting of a successful partnership between NASA Goddard Space Flight Center (GSFC), The Open University, NASA, and ESA. PITMS was designed to measure the abundance and temporal variability of volatile species in the near-surface lunar exosphere from a landed platform on the lunar surface. The PITMS instrument consisted of a European Space Agency–provided Exospheric Mass Spectrometer (including sensor, electronics, controller, and power supply boards) and a GSFC wrapper that provided structural elements, thermal control, and a deployable dust cover. PITMS was designed to operate as a passive sampler, where ambient gases would enter PITMS through an aperture, diffuse around the mass analyzer cavity, become ionized by electron impact and trapped in an RF field, and then sequentially be released to a detector to build a mass spectrum. PITMS was capable of measuring species with a mass-to-charge ratio ( m / z ) from 10 to 150 Da, with a mass resolution of approximately 0.5 amu. The PITMS science investigation was planned to be operated by GSFC with an international team of scientists. Though the mission did not achieve its lunar landing, information about the PITMS instrument and planning is provided to be able to understand and effectively use data that will be forthcoming from the investigation.

Regulator of TElomere Length Helicase 1 (RTEL1) is a helicase required for telomere maintenance and genome replication and repair. RTEL1 has been previously shown to participate in the nuclear export of small nuclear RNAs. Here we show that RTEL1 deficiency leads to a nuclear envelope destabilization exclusively in cells entering S-phase and in direct connection to origin firing. We discovered that inhibiting protein import also leads to similar, albeit non-cell cycle-related, nuclear envelope disruptions. Remarkably, overexpression of wild-type RTEL1, or of its C-terminal part lacking the helicase domain, protects cells against nuclear envelope anomalies mediated by protein import inhibition. We identified distinct domains in the C-terminus of RTEL1 essential for the interaction with KPNB1 (importin β) and NUP153, respectively, and we demonstrated that, on its own, the latter domain can promote the dynamic nuclear internalization of peptides that freely diffuse through the nuclear pore. Consistent with putative functions exerted in protein import, RTEL1 can be visualized on both sides of the nuclear pore using high-resolution microscopy. In all, our work points to an unanticipated, helicase-independent, role of RTEL1 in connecting both nucleocytoplasmic trafficking and nuclear envelope integrity to genome replication initiation in S-phase.

Obesity is strongly associated with mortality and morbidity, but there is a lack of data on its impact on health-related quality of life (HRQoL) across different age groups. Therefore, this study’s objective was to determine the association between body mass index (BMI) and HRQoL in the Austrian adult population based on age groups using the 36-Item Short Form (SF-36) survey. Methods: The SF-36 survey was sent to 500 randomly assigned Austrian adults (response rate: 80.6%). This study assessed HRQoL subscale and component scores based on gender, level of education, smoking status, and alcohol consumption in 403 participants. Results: Increasing BMI is associated with a negative impact on all domains of physical health and social function. The study uncovered substantial variations in the impact of increasing BMI on HRQoL across different age groups, with a pronounced effect observed in the physical components, particularly among individuals aged 65–74. Conclusions: BMI is negatively associated with the physical aspects of HRQoL and social function, affecting various adult age groups differently. Consequently, our results emphasize assessing different age groups and possible influencing factors on HRQoL, such as BMI, for further optimization in designing prevention programs against obesity.

Aim Internal fixation of femoral neck fractures is a widely used procedure that is comparatively less invasive and faster than hip replacement. While head preserving internal fixation of these fractures are still preferred where feasible, a faster recovery and lower reoperation rates make arthroplasty increasingly more appealing, in spite of being a more invasive option. Our aim was to determine the reoperation rate after internal fixation at our institution and to explore relevant risk factors in a geriatric population. Methods This monocentric follow-up study was conducted analyzing 116 patients aged 65 and older with femoral neck fractures who were surgically treated with either cancellous screws or dynamic hip screws between 2010 and 2017. We retrospectively collected longitudinal data from our patient database, supplemented by a telephone survey, with a follow-up period of at least 18 months. Results Twenty reoperations, due to either a failure of fixation, avascular necrosis, or posttraumatic osteoarthritis, were identified in our cohort, which constituted a reoperation rate of 17.2% (20/116). Fracture displacement was significantly associated with the reoperation risk (HR 8, CI 3-20; P < .001). The reoperation rate was 52.2% in displaced fractures vs 8.9% in undisplaced fractures. No link was found between the reoperation rate and gender, age, BMI, ASA score, type of implant, quality of internal fixation, type of living accommodation, and pre-fracture mobility. Conclusion Internal fixation has been found to be an effective option in elderly patients with undisplaced fractures regardless of their specific age, cognitive ability or physical condition. In displaced fractures the reoperation rate was found to be high, therefore a primary hip replacement should be recommended.

Abstract. Introduction: The media coverage of high-profile sporting events can bring increased pressure to athletes’ psychological wellbeing. There may be speculation regarding athletes’ mental state before, during and after competition potentially impacting on both the athlete’s wellbeing and public perception of the individual if a negative tone is attached to an article. As mental health understanding and literacy develop, media reporting of elite athlete mental health may contribute to shaping of opinions and help seeking behaviour. Thus, we have aimed to understand and analyse the tone and content of media reporting on a high-profile sporting event using qualitative methods to explore key aspects of the articles sampled. Methods: We selected two UK broadsheet newspapers available online (The Guardian and The Telegraph) and identified all text articles including the terms “Mental Health” and “Olympics” or “Paralympics” published between 23rd July 2019 and 30th November 2021. We selected articles relevant to the Tokyo 2020 Olympic and Paralympic Games and including mental health as a subject. Relevant articles were read in full, and we conducted a thematic analysis to explore how mental health was portrayed. Results: 581 results were generated from our initial search. Following screening and removal of irrelevant articles, we had 95 articles for analysis. We identified four themes relating to portrayal of mental health: Pressure, impact of COVID, Lack of specific diagnostic terms, and athletes as humans. Conclusion: Media portrayal of mental health at the Tokyo Games was generally positive and portrayed athletes as relatable, inspiring, and “human” rather than superhuman. Reporting particularly focused on athlete-specific factors in mental health conditions and the pressures of high-level competition.

Abstract In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P 0.5 (40 versus 21 days, P = 0.15) and platelet > 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P

After the successful detection of cosmic high-energy neutrinos, the field of multiwavelength photon studies of active galactic nuclei (AGN) is entering an exciting new phase. The first hint of a possible neutrino signal from the blazar TXS 0506+056 leads to the anticipation that AGN could soon be identified as point sources of high-energy neutrino radiation, representing another messenger signature besides the established photon signature. To understand the complex flaring behavior at multiwavelengths, a genuine theoretical understanding needs to be developed. These observations of the electromagnetic spectrum and neutrinos can only be interpreted fully when the charged, relativistic particles responsible for the different emissions are modeled properly. The description of the propagation of cosmic rays in a magnetized plasma is a complex question that can only be answered when analyzing the transport regimes of cosmic rays in a quantitative way. In this paper, therefore, a quantitative analysis of the propagation regimes of cosmic rays is presented in the approach that is most commonly used to model non-thermal emission signatures from blazars, i.e., the existence of a high-energy cosmic-ray population in a relativistic plasmoid traveling along the jet axis. It is shown that in the considered energy range of high-energy photon and neutrino emission, the transition between diffusive and ballistic propagation takes place, significantly influencing not only the spectral energy distribution, but also the lightcurve of blazar flares.