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Abstract Background The COVID-19 pandemic has had an unparalleled impact, precipitating not only direct threats to physical health but also widespread economic and psychological challenges. This study aims to explore the dynamics of coping behaviour and psychological distress (PD) across different phases of the pandemic within an adult general population sample, spanning Austria and Italy. Methods An online questionnaire-based panel study was conducted between 2020 and 2023 including three measurements. We collected data on sociodemographic variables, coping responses (Brief COPE), and PD (Brief-Symptom-Checklist). Statistical analyses were conducted within a linear-mixed-model framework. Multiple imputation and sensitivity analysis were applied to validate the results obtained by complete case analysis. Results The study follows 824 participants and reveals a marginal decrease in overall PD from the first to the second follow-up, particularly in clinically relevant phobic anxiety (35.6% and 34.5% to 25.4%). Most coping behaviours exhibited stable mean-levels with intra-individual variability across the study period. Maladaptive coping strategies were consistently linked to increased PD, whereas adaptive strategies were associated with decreased PD. Conclusion Our findings underscore the complex nature of coping behaviours and PD during and after the pandemic, suggesting that while mean-levels of PD and coping responses remained relatively stable, most coping strategies were subject to intra-individual change. Maladaptive strategies were associated with increased PD, pinpointing to the need for interventions that establish the foundation for adaptive coping mechanisms and promote their application. Further research should explore the reciprocal influences of mental health on coping behaviour, incorporating interventional designs to unravel the nuances of these relationships.

Abstract Background The demand for natural product-based treatment options for livestock is increasing by animals’ owners, veterinarians and policy makers. But at the same time, the traditional knowledge about it is at risk of falling into oblivion in Europe. The present study recorded this knowledge for the linguistically and geographically interesting Swiss canton of Valais. Method Open, semi-structured interviews were used to collect detailed information on formulations and applications, including plant species and natural substances, origin of material, extraction and preparation of herbal products, indication and type of application, dosage, sources of knowledge, frequency of usage and self-assessment of the treatment. Results and discussion In the course of 43 interviews, 173 homemade single species herbal remedy report (HSHR) were recorded. They included 53 plant species from 30 botanical families. Plant species from the botanical families of Asteraceae, Rubiaceae and Cupressaceae were mentioned the most, while the most frequently documented plant species were Coffea arabica L., Juniperus sabina L., Arnica montana L. and Matricaria chamomilla L. For the 173 HSHR, a total of 215 uses were mentioned, most of which were for the treatment of gastrointestinal and metabolic disorders, followed by skin lesions and genito-urinary tract problems. Regional peculiarities emerged, such as the use of Leontopodium alpinum Cass. for diarrhea in the French-speaking Valais, while Matricaria chamomilla and Camellia sinensis L. were used in the German-speaking part instead. In comparison with other regions of Switzerland, 10 plants were reported for the first time, including Juniperus sabina with 18 use reports. Conclusion The daily use on farms and the high satisfaction of farmers with homemade herbal remedies demonstrate their high practical relevance. In conclusion, the traditional regional knowledge about the use of medicinal plants is not only a cultural heritage worth protecting, but also an essential resource for the further development of European veterinary medicine.

Confluences are dynamic morphological nodes that are found in all river networks. In mountain regions, they are influenced by hydraulic and sedimentary processes that occur in steep channels during extreme events in small watersheds. Sediment transport in the tributary channel and aggradation in the confluence can be massive, potentially causing overbank flooding and sedimentation into adjacent settlement areas. Previous works dealing with confluences have mainly focused on lowland regions, and those that have focused on mountain areas have used sediment concentrations and channel gradients that are largely under-representative of mountain river conditions. The presented work contributes to filling this research gap with 45 experiments that use a large-scale physical model. Geometric model parameters, the applied grain size distribution, and the considered discharges represent the conditions at 135 confluences in South Tyrol (Italy) and Tyrol (Austria). The experimental program allowed for a comprehensive analysis of the effects of (i) the confluence angle, (ii) the tributary gradient, (iii) the channel discharges, and (iv) the tributary sediment concentration. In contrast to most research dealing with confluences, results indicate that, in the presence of an intense tributary sediment supply and a small tributary-to-main-channel discharge ratio (0.1), the confluence angle does not have a decisive effect on confluence morphology. Adjustments to the tributary channel gradient yielded the same results. A reoccurring range of depositional geomorphic units was observed in which a deposition cone transitioned to a bank-attached bar. The confluence morphology and tributary channel gradient rapidly adjusted, tending towards an equilibrium state to accommodate both water discharges and the sediment load from the tributary. Statistical analyses demonstrated that the confluence morphology was controlled by the combined channel discharge and the depositional or erosional extent was controlled by the sediment concentration. Applying conclusions drawn from lowland confluence dynamics could misrepresent depositional and erosional patterns and the related flood hazard at mountain river confluences.

Introduction & Purpose The prevalence of smoking among people with mental illness is two to four times higher than in the general population. Unsuccessful quit attempts, often due to low confidence in their ability to quit, suggest that smokers with mental illness may benefit from additional smoking cessation strategies (Mann-Wrobel et al., 2011). Exercise as an adjunct treatment for smoking cessation in healthy individuals is increasingly recommended in the literature (Ussher et al., 2019), but there is limited data for people with mental illness. Therefore, the aim of this study is to evaluate the effectiveness of an exercise program as an add-on therapy for smoking cessation in people with mental illness. Methods 66 smokers with a diagnosed mental illness or mood disorders were included in a randomized controlled trial and received a standardized group smoking cessation program. Out of these 66 smokers, 38 individuals additionally participated in an exercise group (Nordic walking) and 28 in a control group (social contact group discussing health issues). Outcome variables were assessed by questionnaires at baseline (data available for 59 participants: 32 exercise group, 27 control group), during (after 3 weeks), and at the end of the program (5 weeks). Results The study had a dropout rate of 32%. At the end of the program, the abstinence rate was 19% in the exercise group and 30% in the control group (intention-to-treat analysis). There were no significant time-by-group interaction effects for any outcome variables. Significant group differences were found after 3 weeks for internal stimuli of self-efficacy (smokers’ confidence to resist smoking in certain situations; p = 0.026, ƞ² = 0.121) and after 5 weeks for frequency (p = 0.003, ƞ² = 0.210) and intensity (p = 0.007, ƞ² = 0.174) of cigarette craving. The control group showed higher self-efficacy and lower frequency and intensity of cigarette craving compared to the exercise group. Main effects over time were observed in both groups with improvement in several outcome variables (e.g., self-efficacy, positive affect, frequency, and intensity of cigarette craving). Discussion Group differences may be explained by pre-existing differences in cigarette dependence, motivation to quit, and BMI at baseline. It is known from the literature that higher cigarette dependence can lead to less successful quitting and higher relapse rates (Gierisch et al., 2012). Participants also had difficulty integrating program content into their daily lives and had low attendance rates. According to Zhou et al. (2023), a higher adherence rate would lead to a higher quit rate. Since the study was conducted in groups, the influence of group dynamics on motivation to quit smoking needs to be considered. Conclusion An additional effect of exercise as an adjunctive therapy in smoking cessation could not be confirmed, since the control group showed better outcome scores. Due to the high dropout rate, further studies with larger samples are needed. Improving access to smoking cessation programs, developing additional strategies, integrating evidence-based treatment into existing settings, and training health care professionals to engage people with mental illness in smoking cessation remain important areas for improvement (Falcaro et al., 2021). References Falcaro, M., Osborn, D., Hayes, J., Coyle, G., Couperthwaite, L., Weich, S., & Walters, K. R. (2021). Time trends in access to smoking cessation support for people with depression or severe mental illness: A cohort study in English primary care. BMJ Open, 11(12), Article e048341. https://doi.org/10.1136/bmjopen-2020-048341 Gierisch, J. M., Bastian, L. A., Calhoun, P. S., McDuffie, J. R., & Williams, J. W. (2012). Smoking cessation interventions for patients with depression: A systematic review and meta-analysis. Journal of General Internal Medicine, 27(3), 351–360. https://doi.org/10.1007/s11606-011-1915-2 Mann-Wrobel, M. C., Bennett, M. E., Weiner, E. E., Buchanan, R. W., & Ball, M. P. (2011). Smoking history and motivation to quit in smokers with schizophrenia in a smoking cessation program. Schizophrenia Research, 126(1-3), 277–283. https://doi.org/10.1016/j.schres.2010.10.030 Ussher, M. H., Faulkner, G. E. J., Angus, K., Hartmann-Boyce, J., & Taylor, A. H. (2019). Exercise interventions for smoking cessation. The Cochrane Database of Systematic Reviews, 2019(10), Article CD002295. https://doi.org/10.1002/14651858.CD002295.pub6 Zhou, Y., Feng, W., Guo, Y., & Wu, J. (2023). Effect of exercise intervention on smoking cessation: A meta-analysis. Frontiers in Physiology, 14, Article 1221898. https://doi.org/10.3389/fphys.2023.1221898

Background There are different modes and ways to assess patient-reported outcomes (PROs) in clinical trials. However, there is little systematic information on how often different modes of assessment (MOA) are used in cancer clinical trials and how exactly assessments are conducted. The goal of this scoping review is to gain an understanding of the MOA and data management of PROs in cancer randomised controlled trials (RCTs) and the reporting quality thereof.Methods and analysis This scoping review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant trials will be identified via their indexed publications. We will search PubMed for RCTs conducted in cancer populations that evaluate a biomedical treatment with a PRO endpoint. Trials with publications published between January 2019 and November 2023 will be included. Two independent reviewers will review the references for both the abstract and full-text screening. We will extract data from the publications from a trial and the trial protocol if a protocol can be traced. Data will be summarised at the trial level. We will focus on a descriptive analysis of the MOA of PROs and on the relative frequencies of the different MOA. We will also evaluate the quality of reporting for the relevant SPIRIT and CONSORT guidelines that refer to the assessment of PROs in trials. Due to the scoping nature of our review, we will not perform a dedicated quality assessment of all trials.Ethics and dissemination The proposed review is based on secondary, published data. Hence, no ethics review is necessary. The review is part of an ongoing project on the use of electronic data capture methods in cancer clinical trials. The findings from the review will support the project and contribute to synthesising guidance to ultimately improve the (electronic) measurement of patient-reported outcome measures in clinical trials.

Kidney transplantation is a life-saving intervention for end-stage renal disease; yet, the persistent gap between organ demand and supply remains a significant challenge. This paper explores the escalating discard rates of deceased donor kidneys in the United States to assess trends, discard reasons, demographical differences, and preservation techniques. Data from the Scientific Registry of Transplant Recipients from 2010 to 2021 was analyzed using chi-squared tests for trend significance and logistic regression to estimate odds ratios for kidney discard. Over the last decade, discard rates have risen to 25% in 2021. Most discarded kidneys came from extended criteria donor (ECD) donors and elevated kidney donor profile index (KDPI) scores. Kidney biopsy status was a significant factor and predictor of discard. Discard rates varied greatly between Organ Procurement and Transplantation Network regions. Of reasons for discard, “no recipient located” reached a high of 60%. Additionally, there has been a twofold increase in hypothermic machine perfusion (HMP) since 2010, with transportation difficulties being the main reason for the discard of perfused kidneys. Our findings suggest a need to recalibrate organ utilization strategies, optimize the use of lower-quality kidneys through advanced preservation methods, and address the evolving landscape of organ allocation policies to reduce kidney discard rates.

Abstract Background The use of open-ended questions supplementing static questionnaires with closed questions may facilitate the recognition of symptoms and toxicities. The open-ended ‘Write In three Symptoms/Problems (WISP)’ instrument permits patients to report additional symptoms/problems not covered by selected EORTC questionnaires. We evaluated the acceptability and usefulness of WISP with cancer patients receiving active and palliative care/treatment in Austria, Chile, France, Jordan, the Netherlands, Norway, Spain and the United Kingdom. Methods We conducted a literature search on validated instruments for cancer patients including open-ended questions and analyzing their responses. WISP was translated into eight languages and pilot tested. WISP translations were pre-tested together with EORTC QLQ-C30, QLQ-C15-PAL and relevant modules, followed by patient interviews to evaluate their understanding about WISP. Proportions were used to summarize patient responses obtained from interviews and WISP. Results From the seven instruments identified in the literature, only the free text collected from the PRO-CTAE has been analyzed previously. In our study, 161 cancer patients participated in the pre-testing and interviews (50% in active treatment). Qualitative interviews showed high acceptability of WISP. Among the 295 symptoms/problems reported using WISP, skin problems, sore mouth and bleeding were more prevalent in patients in active treatment, whereas numbness/tingling, dry mouth and existential problems were more prevalent in patients in palliative care/treatment. Conclusions The EORTC WISP instrument was found to be acceptable and useful for symptom assessment in cancer patients. WISP improves the identification of symptoms/problems not assessed by cancer-generic questionnaires and therefore, we recommend its use alongside the EORTC questionnaires.

BackgroundResection of colorectal liver metastasis is the standard of care for patients with Stage IV CRC. Despite undoubtedly improving the overall survival of patients, pHx for colorectal liver metastasis frequently leads to disease recurrence. The contribution of this procedure to metastatic colorectal cancer at a molecular level is poorly understood. We designed a mouse model of orthograde metastatic colorectal cancer (CRC) to investigate the effect of partial hepatectomy (pHx) on tumor progression.MethodsCRC organoids were implanted into the cecal walls of wild type mice, and animals were screened for liver metastasis. At the time of metastasis, 1/3 partial hepatectomy was performed and the tumor burden was assessed longitudinally using MRI. After euthanasia, different tissues were analyzed for immunological and transcriptional changes using FACS, qPCR, RNA sequencing, and immunohistochemistry.ResultsMice that underwent pHx presented significant liver hypertrophy and an increased overall metastatic load compared with SHAM operated mice in MRI. Elevation in the metastatic volume was defined by an increase in de novo liver metastasis without any effect on the growth of each metastasis. Concordantly, the livers of pHx mice were characterized by neutrophil and bacterial infiltration, inflammatory response, extracellular remodeling, and an increased abundance of tight junctions, resulting in the formation of a premetastatic niche, thus facilitating metastatic seeding.ConclusionsRegenerative pathways following pHx accelerate colorectal metastasis to the liver by priming a premetastatic niche.

Background:. Organ shortage remains a major challenge for the field of transplantation. Maximizing utilization and minimizing discard of available organs is crucial to reduce waitlist times. Our aim was to investigate the landscape of liver recovery, discard over the past decade in the United States, and identify areas to reduce organ discard. Methods:. This study used the Scientific Registry of Transplant Recipients United Network for Organ Sharing database to analyze the rates and associated reasons of discarded organs from 2010 to 2021. All deceased donors were evaluated, and data were analyzed by organ type, year, and region. Organ disposition was analyzed by year and region. Donor demographics and liver biopsy data were also analyzed. Results:. The volume of liver transplantation increased steadily, with a 44% increase from 2010 to 2021. Donation after circulatory death transplantation increased by 239%, comprising 10.6% of transplants in 2021, yet discard rates remained high at 30% for this donor subset. For all donor types, the liver discard rate has remained stable around 10% despite a 74% increase in available donors. Seventy percent of liver discards were attributed to organ factors, with biopsy findings accounting for 40% of all discards. Of livers that were biopsied, 70% had macrosteatosis of

Abstract The hemodynamics in the aorta as well as the durability of aortic valve prostheses vary greatly between different types of devices. Although placement and sizing of surgical aortic valve prostheses are excellent, the valve geometry of common devices cannot be customized to fit the patient’s anatomy perfectly. Similarly, transcatheter aortic valve implantation (TAVI) devices are not customizable and may be orientated unfavorably during implantation. Imperfect fit of an aortic valve prosthesis may result in suboptimal performance and in some cases the need for additional surgery. Leveraging the advent of precision, multi-material 3D-printing, a bioinspired silicone aortic valve was developed. The manufacturing technique makes it fully customizable and significantly cheaper to develop and produce than common prostheses. In this study, we assess the hemodynamic performance of such a 3D-printed aortic valve and compare it to two TAVI devices as well as to a severely stenosed valve. We investigate the blood flow distal to the valve in an anatomically accurate, compliant aorta model via three-dimensional particle tracking velocimetry measurements. Our results demonstrate that the 3D-printed aortic valve induces flow patterns and topology compatible with the TAVI valves and showing similarity to healthy aortic blood flow. Compared to the stenosis, the 3D-printed aortic valve reduces turbulent kinetic energy levels and irreversible energy losses by over 75%, reaching values compatible with healthy subjects and conventional TAVIs. Our study substantiates that the 3D-printed heart valve displays a hemodynamic performance similar to established devices and underscores its potential for driving innovation towards patient specific valve prostheses.

Abstract In the race to curb energy and oil consumption, zeroing of wall frictional forces is highly desirable. The turbulent skin friction drag at the solid/liquid interface is responsible for substantial energy losses when conveying liquids through hydraulic networks, contributing approximately 10% to the global electric energy consumption. Despite extensive research, efficient drag reduction strategies effectively applicable in different flow regimes are still unavailable. Here, we use a wall-attached magnetic fluid film to achieve a wall drag reduction of up to 90% in channel flow. Using optical measurements supported by modelling, we find that the strong damping of wall friction emerges from the co-existence of slip and waviness at the coating interface, and the latter is a key factor to obtain almost complete wall drag reduction across laminar and turbulent flow regimes. Our magnetic fluid film is promising and ready to be applied in energy-saving and antifouling strategies in fluid transport and medical devices.

Support teachers are responsible for educating students with disabilities who have complex needs and require additional resources. Because of the highly stressful nature of the role, support teachers are at greater risk of professional burnout, higher attrition rates, and impacts on wellbeing. There is a distinct lack of Australian or state/territory empirical evidence on strategies to promote support teacher wellbeing. In this exploratory qualitative study, we applied thematic analysis to interviews of Tasmanian support teachers to find that their wellbeing relies on principals' and leadership staff's support and implementation of wellbeing and inclusive education practices. Support teachers are experiencing stress, anxiety, emotional exhaustion, and depression caused by workload, accountability for funding, and poor leadership. School leaders who value wellbeing and inclusive practices foster a positive culture, demonstrating ecological theory. This study marks an initial step towards understanding how to nurture the support teachers of Tasmania.

The rapid expansion of public-school preschool programs significantly challenges America's school administrators, teachers, and school professionals. The complex issues of preschool mental health needs, expulsion, and suspension are at the forefront. In the United States, schools are reporting rapidly increasing numbers of preschool programs, primarily in the form of 3K, 4K, and inclusion programs. This dramatic increase of young children in the public schools is a result of (a) research on the long-term cognitive and social benefits of high-quality early childhood programs, (b) federal and state legislation supporting state-funded preschool education, and (c) the continued need to support working parents via public-funded education for their young children. This article is a review of the research on preschool mental health and early trauma from adverse childhood experiences (ACEs), the impact of suspension and expulsion on preschool children, and the benefits of high-quality preschool programs in the public schools. Also included is a review of current policies and practices in exemplary public-school preschool programs related to mental health services, ACEs, suspension, and expulsion. Recommendations for future policy and practices for the preschool population are presented. Appendix B provides resources for school administrators and professionals.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004–2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3–8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

BackgroundOver the past years, the COVID-19 pandemic has caused significant disruptions in daily routines. Although the pandemic has affected almost everyone, it has been particularly challenging for people with pre-existing mental health conditions. Therefore, this study investigated the long-term impact of resilience and extraversion on psychological distress in individuals diagnosed with mental health disorders (MHD) compared to the general population. In addition, possible gender-specific differences were investigated.Methods123 patients with pre-existing MHD and 343 control subjects from Austria and Italy participated in three online surveys that had been conducted after the initial wave of the COVID-19 pandemic (t0), during the second lockdown in both countries (t1), and one year thereafter (t2). Participants completed standardized questionnaires on psychological distress (Brief-Symptom-Checklist), resilience (Resilience Scale), and extraversion (Big Five Inventory). A mediation model was employed to test the primary hypothesis. Possible gender-specific differences were analyzed using a moderated mediation model.ResultsThe prevalence of psychological distress was consistently higher in patients compared to controls (t0: 37.3% vs. 13.2%, t1: 38.2% vs 11.7%, t2: 37.4% vs. 13.1%). This between-group difference in psychological distress at the first follow-up was fully mediated by baseline resilience scores (65.4% of the total effect). During the second-follow up, extraversion accounted for 18% of the total effect, whereas resilience slightly decreased to 56% of the total effect. Gender was not a significant moderator in the model.ConclusionNext to showing that people with MHD were particularly affected by the pandemic, these findings indicate that higher degrees of resilience and extraversion are related to less long-term psychological distress. Our findings stress the relevance of strengthening resilience and extraversion and to provide mental health support in times of crises, both to patients with MHD and the general population.

Abstract The 10-item Kessler Psychological Distress scale (K10) and its 6-item short-form version (K6) measure psychological distress, particularly anxiety or depressive symptoms. While these questionnaire scales are widely used in various settings and populations, general population normative data are rarely available. To facilitate the interpretation of K10 and K6 scores, we provide normative general population data from seven European countries. We used an online survey to collect K10 data from general population samples in Austria, Italy, Germany, France, the Netherlands, Poland and Spain. We calculated the age- and sex-specific normative values separately for each country. For more specific estimates of K10 and K6 scores for individuals or groups, we also established a multivariable regression model based on socio-demographic and health data. In total, N = 7,087 adults participated in our study (51.6% women; mean age, 49.6 years). The mean K10 score in the total sample was 8.5 points (standard deviation, 7.3) on 0–40 points metric, with mean scores in individual countries ranging from 6.9 (the Netherlands) to 9.9 (Spain). Women showed higher scores than men and younger participants scored higher than older participants. Our study is the first to present normative K10 and K6 data from several European countries using a consistent sampling approach. These reference values will facilitate the interpretation of K10 and K6 scores in clinical research and practice and also highlight the variation in psychological distress levels across countries and groups according to their socio-demographic and health characteristics.

Background & aimsUnited Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown.MethodsIn this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019.ResultsProbability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%.ConclusionIn this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.

Abstract Countless processes in nature and industry, from rain droplet nucleation to plankton interaction in the ocean, are intimately related to turbulent fluctuations of local concentrations of advected matter. These fluctuations can be described by considering the change of the separation between particle pairs, known as pair dispersion, which is believed to obey a cubic in time growth according to Richardson’s theory. Our work reveals a universal, scale-invariant alignment between the relative velocity and position vectors of dispersing particles at a mean angle that we show to be a universal constant of turbulence. We connect the value of this mean angle to Richardson’s traditional theory and find agreement with data from a numerical simulation and a laboratory experiment. While the Richardson’s cubic regime has been observed for small initial particle separations only, the constancy of the mean angle manifests throughout the entire inertial range of turbulence. Thus, our work reveals the universal nature of turbulent pair dispersion through a geometrical paradigm whose validity goes beyond the classical theory, and provides a framework for understanding and modeling transport and mixing processes.

Abstract Carbon efflux from soils is the largest terrestrial carbon source to the atmosphere, yet it is still one of the most uncertain fluxes in the Earth’s carbon budget. A dominant component of this flux is heterotrophic respiration, influenced by several environmental factors, most notably soil temperature and moisture. Here, we develop a mechanistic model from micro to global scale to explore how changes in soil water content and temperature affect soil heterotrophic respiration. Simulations, laboratory measurements, and field observations validate the new approach. Estimates from the model show that heterotrophic respiration has been increasing since the 1980s at a rate of about 2% per decade globally. Using future projections of surface temperature and soil moisture, the model predicts a global increase of about 40% in heterotrophic respiration by the end of the century under the worst-case emission scenario, where the Arctic region is expected to experience a more than two-fold increase, driven primarily by declining soil moisture rather than temperature increase.

The Hedgehog (HH) pathway is crucial for embryonic development, and adult homeostasis. Its dysregulation is implicated in multiple diseases. Existing cellular models used to study HH signal regulation in mammals do not fully recapitulate the complexity of the pathway. Here we show that Spinal Cord Organoids (SCOs) can be applied to quantitively study the activity of the HH pathway. During SCO formation, the specification of different categories of neural progenitors (NPC) depends on the intensity of the HH signal, mirroring the process that occurs during neural tube development. By assessing the number of NPCs within these distinct subgroups, we are able to categorize and quantify the activation level of the HH pathway. We validate this system by measuring the effects of mutating the HH receptor PTCH1 and the impact of HH agonists and antagonists on NPC specification. SCOs represent an accessible and reliable in-vitro tool to quantify HH signaling and investigate the contribution of genetic and chemical cues in the HH pathway regulation.