Search

BackgroundThe cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs.MethodsWe identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer-related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life-years gained system-wide were calculated from the difference in adjusted 5-year restricted mean survival times.ResultsThere were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54-0.58, p

PurposeReal world evidence is crucial to understanding the diffusion of new oncologic therapies, monitoring cancer outcomes, and detecting unexpected toxicities. In practice, real world evidence is challenging to collect rapidly and comprehensively, often requiring expensive and time-consuming manual case-finding and annotation of clinical text. In this Review, we summarise recent developments in the use of artificial intelligence to collect and analyze real world evidence in oncology.MethodsWe performed a narrative review of the major current trends and recent literature in artificial intelligence applications in oncology.ResultsArtificial intelligence (AI) approaches are increasingly used to efficiently phenotype patients and tumors at large scale. These tools also may provide novel biological insights and improve risk prediction through multimodal integration of radiographic, pathological, and genomic datasets. Custom language processing pipelines and large language models hold great promise for clinical prediction and phenotyping.ConclusionsDespite rapid advances, continued progress in computation, generalizability, interpretability, and reliability as well as prospective validation are needed to integrate AI approaches into routine clinical care and real-time monitoring of novel therapies.

Abstract All-perovskite tandem photovoltaics are a potentially cost-effective technology to power chemical fuel production, such as green hydrogen. However, their application is limited by deficits in open-circuit voltage and, more challengingly, poor operational stability of the photovoltaic cell. Here we report a laboratory-scale solar-assisted water-splitting system using an electrochemical flow cell and an all-perovskite tandem solar cell. We begin by treating the perovskite surface with a propane-1,3-diammonium iodide solution that reduces interface non-radiative recombination losses and achieves an open-circuit voltage above 90% of the detailed-balance limit for single-junction solar cells between the bandgap of 1.6–1.8 eV. Specifically, a high open-circuit voltage of 1.35 V and maximum power conversion efficiency of 19.9% are achieved at a 1.77 eV bandgap. This enables monolithic all-perovskite tandem solar cells with a 26.0% power conversion efficiency at 1 cm2 area and a pioneering photovoltaic-electrochemical system with a maximum solar-to-hydrogen efficiency of 17.8%. The system retains over 60% of its peak performance after operating for more than 180 h. We find that the performance loss is mainly due to the degradation of the photovoltaic component. We observe severe charge collection losses in the narrow-bandgap sub-cell that can be attributed to the interface degradation between the narrow-bandgap perovskite and the hole-transporting layer. Our study suggests that developing chemically stable absorbers and contact layers is critical for the applications of all-perovskite tandem photovoltaics.

Background: This study aimed to identify plasma lipoproteins and small metabolites associated with high risk of malnutrition during intensive care unit (ICU) stay in patients with severe injuries. Methods: This observational prospective exploratory study was conducted at two level-1 trauma centers in the Netherlands. Adult patients (aged ≥18 years) who were admitted to the ICU for more than 48 h between July 2018 and April 2022 owing to severe injuries (polytrauma, as defined by Injury Severity Scores of ≥16) caused by blunt trauma were eligible for inclusion. Partial least squares discriminant analysis was used to analyze the relationship of 112 lipoprotein-related components and 23 small metabolites with the risk of malnutrition (modified Nutrition Risk in Critically Ill score). Malnutrition was diagnosed based on Subjective Global Assessment scores. The relationship of lipoprotein properties and small metabolite concentrations with malnutrition (during ICU admission) was evaluated using mixed effects logistic regression. Results: Overall, 51 patients were included. Lower (very) low-density lipoprotein ([V]LDL) (free) cholesterol and phospholipid levels, low particle number, and higher levels of LDL triglycerides were associated with a higher risk of malnutrition (variable importance in projection [VIP] value >1.5). Low levels of most (V)LDL and intermediate-density lipoprotein subfractions and high levels of high-density lipoprotein Apo-A1 were associated with the diagnosis of malnutrition (VIP value >1.5). Increased levels of dimethyl sulfone, trimethylamine N-oxide, creatinine, N, N-dimethylglycine, and pyruvic acid and decreased levels of creatine, methionine, and acetoacetic acid were also indicative of malnutrition (VIP value >1.5). Overall, 14 lipoproteins and 1 small metabolite were significantly associated with a high risk of malnutrition during ICU admission (P

An atraumatic approach to the inner ear is an important goal in the future development of cochlear implant surgery, as the current surgical procedure for electrode insertion is highly invasive. To reduce invasiveness, minimally invasive surgical options are being explored, such as the insertion of one or more drill channels. Due to the proximity to critical structures, a temperature sensor is incorporated into the medical drill for process parallel temperature monitoring to prevent thermal damage. The temperature data is sent to the analysis hardware via Bluetooth BLE. This requires a power supply for the electronics on the drill. There are a number of limitations to the design of such a power supply. For one, the drill is rotating. Therefore, the energy generation must be contactless. Secondly, the energy generation should not depend on the rotation of the drill, so that the temperature can be measured even without the drill rotating and the rotational speed of the drill is not limited. In this paper, we propose a solution for a contactless energy transmission system (ETS) based on inductive coupling. Considering the dimensional limitations of attaching the electronics to the drill shaft, a multilayer PCB coil with multiple contacts for different number of turns is developed. The electrical circuit is simulated and the best settings are identified. The power supply is validated according to the predefined requirements. In the future, the medical drill will be built with the newly developed ETS. Sterilization and wear tests are performed to confirm the suitability of the drill with integrated temperature sensor for the operating room.

Objectives: Studies have shown temporal changes in post-acute sequelae of COVID-19 (PASC) prevalence for early SARS-CoV-2 variants, although often lacking controls. This prospective study assesses the prevalence of symptoms in Delta- and Omicron-infected cases up to 12 months compared with population controls. Methods: Adult participants filled out surveys every 3 months (T0-T12) between July 2021 and August 2023. Cases were recruited with a positive SARS-CoV-2 test during the Delta or Omicron domination. Population controls were randomly invited from the Dutch Personal Records Database. Participants indicated the presence of 13 PASC-associated symptoms, and severity scores of fatigue, cognitive impairment, dyspnea, and pain. PASC prevalence was defined as the excess prevalence of havingat least one PASC-associated symptom in cases compared with population controls. Results: PASC prevalence was 34.3% at T3 and decreased to 21.7% at T12 for Delta and decreased from 18.7% at T3 to 16.7% at T12 for Omicron. At T12, the difference between Delta and Omicron was not significant. Delta cases generally had higher excess symptom scores for fatigue, dyspnea, and cognitive impairment than Omicron. Conclusions: In the first 9 months after infection, PASC prevalence was higher for Delta than Omicron, but the difference reduced over time and approximated after 12 months.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: Nitinol is a metal alloy with high elastic flexibility and shape memory characteristics, making it effective in orthopedic surgery. Although nitinol staples have shown similar efficacy to traditional implants for foot and ankle surgery, the literature is limited regarding nitinol screws. The purpose of this study is to determine whether there is a difference in outcomes and complications between nitinol screws and traditional screws used for foot and ankle surgery. Methods: A multicenter retrospective cohort study was conducted for patients who underwent a foot and ankle procedure utilizing traditional compression screws or nitinol compression screws, between February 1st, 2021, and July 1st, 2023. Demographic factors, type of implant, and outcomes were recorded. Student’s t-test and Wilcoxon rank sum test were used to compare continuous variables, while the chi-squared test was used to compare categorical variables. Results: A total of 163 patients were included in the study, with 106 patients treated with traditional screws and 58 treated with nitinol screws. There was no significant difference between those treated with nitinol screws and those treated with traditional screws in complication rate (8.6% vs 11.3%, P=0.78), non-union rate (5.2% vs 8.5%, P=0.54), revision surgeries (1.7% vs 2.8%, P=1), hardware removal (3.4% vs 11.3%, P=0.14), or 90-day hospital readmissions (0% vs 2.8%, P=0.55) for foot and ankle surgery. Conclusion: Our study found no difference in terms of complications or postoperative outcomes between those treated with nitinol screws and those treated with traditional screws for elective foot and ankle procedures. Our findings suggest that nitinol screws appear to be safe and effective for foot and ankle surgery with positive postoperative outcomes and a trend in lower complication and non-union rates. However further investigation is warranted to assess if faster time to union and quicker weight bearing may be possible with this type of fixation.

ABSTRACT Why does the growth of most life forms exhibit a narrow range of optimal temperatures below 40°C? We hypothesize that the recently identified stable range of oceanic temperatures of ~5 to 37°C for more than two billion years of Earth history tightly constrained the evolution of prokaryotic thermal performance curves to optimal temperatures for growth to less than 40°C. We tested whether competitive mechanisms reproduced the observed upper limits of life's temperature optima using simple Lotka–Volterra models of interspecific competition between organisms with different temperature optima. Model results supported our proposition whereby organisms with temperature optima up to 37°C were most competitive. Model results were highly robust to a wide range of reasonable variations in temperature response curves of modeled species. We further propose that inheritance of prokaryotic genes and subsequent co‐evolution with microbial partners may have resulted in eukaryotes also fixing their temperature optima within this narrow temperature range. We hope this hypothesis will motivate considerable discussion and future work to advance our understanding of the remarkable consistency of the temperature dependence of life.

Category: Hindfoot; Ankle Introduction/Purpose: Minimally Invasive Zadek osteotomy (MIS ZO) has been demonstrated to be a safe and effective surgical intervention for patients with Insertional Achilles Tendinopathy (IAT) and Haglund’s deformity. However, there is limited literature to guide surgeons one which patients may be the best candidates for MIS ZO. Severity of IAT on preoperative MRI may correlate with post operative functional outcomes and help guide patient selection for treatment with MIS ZO. The current study evaluated the postoperative outcomes of MIS ZO in patients with various grades of Achilles tendinopathy on preoperative MRI, to determine if severity of disease on preoperative MRI could be predictive of improved functional outcomes after MIS ZO. Methods: Patients who underwent MIS ZO for IAT and Haglund’s deformity were identified and retrospectively analyzed at a mean of 15.59 months follow-up. Achilles pathology was graded as previously described by Nicholson et al. on preoperative MRI. Grade 1 describes anteroposterior diameter of 6-8 mm and nonuniform degeneration; grade 2 describes diameter >8 mm and < 50% uniform tendon degeneration; grade 3 describes tendon diameter >8 mm and uniform degeneration of >50% tendon width. Fourteen patients met our inclusion criteria. Four patients exhibited grade 1 pathology preoperatively, 3 patients exhibited grade 2 pathology preoperatively, and 7 patients exhibited grade 3 pathology preoperatively. Preoperative and postoperative Patient Reported Outcome Measurement Information System (PROMIS) scores, complications, and revisions were recorded for each patient. PROMIS scores were compared using a paired t-test. All other continuous data was compared by Analysis of Variance (ANOVA); all categorical data was compared using Chi-squared analysis. P< 0.05 were considered significant. Results: PROMIS pain score improved postoperatively in patients with grade 1 66.75±5.50 to 59.00±7.75, p=0.036) and grade 3 (69.86±6.17 to 55.71±10.44, p=0.011) Achilles tendinopathy on preoperative MRI. Meanwhile, in patients with grade 2 pathology, PROMIS physical function (38.33±8.50 to 43.67±9.07, p=0.02) improved postoperatively. In the grade three group, 1/7 (14.29%) patients experienced transient neuritis that resolved at 3 months without further treatment and 1/7 (14.29%) patients required revision surgery to an open midline splitting Haglund’s resection. Meanwhile no patients in either the grade one or grade two groups required reoperation, rehospitalization, or complications. 13/14 (93%) patients were very satisfied with their procedure and wound undergo it again. Conclusion: These early data suggest that patients with IAT, regardless of severity, improve after MIS ZO. Therefore, ZO may be a reasonable first line option for all patients presenting with IAT. In our small retrospective study, we were able to demonstrate significant improvement in pain and/or function following ZO in all grades of IAT tendinous pathology on preoperative MRI. This study may help guide surgeons when deciding between MIS ZO and other surgical options for IAT and Haglund’s deformity. Further, large prospective studies are warranted to further investigate outcomes and indications of MIS ZO in patients with IAT and Haglund’s deformity

Category: Hindfoot; Ankle Introduction/Purpose: The Zadek osteotomy (ZO) has been demonstrated to be an effective treatment for patients with Haglund deformity and Insertional Achilles Tendinopathy (IAT). Radiographic measurements are one method of diagnostic criteria that have been utilized to define a more specific patient cohort that is a superior candidate for Zadek intervention. Tourné et al. most recently proposed an X/Y < 2.5 to define candidates that will benefit from the Zadek. However, many clinicians do not consider radiographic measurements to define efficacy of ZO. Additionally, current literature is lacking a direct comparison of ZO efficacy in patients with preoperative X/Y ratios above and below Tourné’s criteria. The current study tested the hypothesis: patients with IAT, regardless of X/Y ratio, would improve in pain and physical function after ZO. Methods: This was a retrospective, multi-center study. Patients underwent ZO at two different institutions, by three different fellowship trained orthopedic foot and ankle surgeons. 48 cases in 46 patients treated with Zadek osteotomy were included in our retrospective analysis. There were 34 cases with preoperative X/Y < 2.5 and 14 cases with preoperative radiographs measuring an X/Y > 2.5. All patients had a minimum of one-year follow-up (mean 23.24±4.82). Pain, function, and mobility PROMIS scores, VAS scores, complications, X/Y ratio measurements, and calcaneal pitch angle measurement were collected preoperatively and at final follow-up appointment. Cases were placed in cohorts based on preoperative X/Y above or below 2.5). T-tests were used to determine statistical differences following ZO. Similarly, chi-squared analysis was used to compare differences in categorical data between our groups. Results: A summary of preoperative and postoperative PROMIS scores, VAS scores, calcaneal pitch measurements, and X/Y ratios can be found in Table 1. Patients with X/Y < 2.5 demonstrated significant improvement in PROMIS pain, function, mobility scores, VAS score, calcaneal pitch angle, and X/Y ratio following ZO intervention (p< 0.05). In comparison, following ZO, patients with X/Y > 2.5 demonstrated significant improvement in PROMIS pain, VAS, and X/Y ratio (p< 0.05). However, in patients with X/Y > 2.5, preoperative VAS scores were higher (p=0.014) and improved to a significantly larger degree (p=0.006). There was one case of minor neuropathy (X/Y > 2.5); there was one patient that required revision to open debridement and repair (X/Y < 2.5). We observed a 98% rate of satisfaction overall following ZO intervention. Conclusion: Zadek osteotomy demonstrated improvement in patients’ pain and excellent patient satisfaction, regardless of their preoperative X/Y ratio on radiograph. However, patients with X/Y ratio < 2.5 did demonstrate significant improvement in patient reported function and mobility scores. Overall, a 98% satisfaction was observed following ZO in all patients. Preoperative X/Y ratio did not seem to determine success of ZO in the treatment of IAT, however, further clinical correlation is needed. to better understand differences if PROMIS physical function and mobility in terms of long-term success of the ZO.

Category: Ankle; Hindfoot Introduction/Purpose: Surgical options for Insertional Achilles Tendinopathy (IAT) and Haglund‘s deformity include the open midline Achilles tendon splitting approach with Haglund’s resection and Achilles debridement and repair. However, many have cited high rates of complications with this approach such as wound dehiscence, infections, and persistent postoperative pain. Alternative surgical management of IAT and Haglund’s deformity includes the Zadek osteotomy (ZO). ZO can be accomplished percutaneously, reducing potential wound complications, pain, and infections. The current study compared outcomes and complications of the open midline Achilles tendon splitting approach with the percutaneous ZO in patients with IAT and Haglund’s deformity. We hypothesized that the percutaneous ZO would allow for improvement in patient reported outcomes, yet less complications in comparison to the traditional, open midline Achilles tendon splitting approach. Methods: Patients who received an open midline Achilles tendon splitting procedure or percutaneous ZO for IAT and Haglund’s deformity were identified and retrospectively analyzed at a minimum of one-year follow-up. 21 patients treated with percutaneous ZO and 45 patients treated with open midline Achilles tendon splitting procedure for IAT and Haglund’s deformity met our inclusion criteria. Patients had average follow up of 23.65±6.87 months. Preoperative Patient Reported Outcome Measurement Information System (PROMIS) scores, postoperative PROMIS scores, complications, and revisions were recorded for each patient. Preoperative and postoperative PROMIS scores were compared using a paired t-test. All other continuous data was compared by t-test; all categorical data was compared using Chi-squared analysis. All p< 0.05 were considered significant. Results: In patients who underwent percutaneous ZO or an open midline Achilles tendon splitting Haglund’s resection, PROMIS function (p< 0.01), pain (p< 0.01), and mobility (p< 0.01) scores improved at 12-month minimum follow-up. In the ZO group, 1/21 (4.6%) patients experienced nerve injury and 1/21 (4.6%) patients required revision surgery to an open midline splitting Haglund’s resection. Meanwhile, 3/45 (6.67%) patients who underwent an open midline Achilles tendon splitting procedure experienced significant postoperative pain, 3/45 (6.67%) wound dehiscence, 3/45 (6.67%) wound infection, and 1/45 (2.22%) nerve injury. 4/45 (8.89%) patients who underwent the open midline Achilles tendon splitting approach required revision. Additionally, 1/45 required hardware removal and 1/45 required incision and debridement. All cause complication were found to be higher in the open midline Achilles tendon splitting approach (p=0.02). Conclusion: There are several surgical treatment options for IAT and Haglund‘s deformity, yet IAT remains a challenging lower extremity disorder to treat. In the current study, both the open, midline Achilles tendon splitting Haglund’s resection and percutaneous ZO led to significant improvement in patient reported outcomes. However, our study demonstrated a significant lower complication and revision in the ZO group. Data presented in this study may guide surgeons’ decision making when choosing suitable treatment options for patients with IAT and Haglund deformity.

Category: Ankle; Basic Sciences/Biologics Introduction/Purpose: Highly cross-linked polyethylene (HXLPE) is the most used bearing material in orthopedic joint replacement because of its reduced wear relative to standard ultra-high molecular weight polyethylene (UHMWPE). Newer generations of HXLPE include antioxidants to improve oxidation resistance and fatigue in addition to reducing wear. There are many ways to manufacture this material, but most commercially available versions are cross-linked via high dose irradiation (>75kGy). The latest concept utilizes a chemical cross-linking process during consolidation of the material. The resultant material has higher fracture toughness than previously tested HXLPE variations. The goal of this study was to evaluate the wear performance of different polyethylene materials. Methods: Wear testing was performed using a total ankle system following ISO-22622 (Wear of total ankle-joint prostheses). The same size constructs were used for all tests only varying the base material used to manufacture the bearing components. There were three polyethylene versions tested: 1) direct compression molded UHMWPE (DCM), 2) gamma cross-linked Vitamin E polyethylene (GXVE), and 3) chemically cross-linked Vitamin E polyethylene (CXVE). DCM and CXVE were gamma sterilized while GXVE was ethylene oxide sterilized. All parts underwent accelerated aging per ASTM F2003 to simulate worst-case oxidation prior to testing. Mass loss measurements were taken after 0.5, 1, 2, 3, 4, and 5-million cycles. The steady-state wear rate is reported as the linear wear-rate from 0.5 million to five-million cycles. Additionally, particle analysis was performed per ASTM F1877 on particulate extracted from the worst samples after five-million cycles. The analysis quantified mean equivalent circle diameter (ECD) and aspect ratio. Results: The steady-state wear rate for the standard UHMWPE, GXVE, and CXVE were 3.77±0.36mg/MC, 1.44±0.22mg/MC, and -0.04±0.19mg/MC respectively. An ANOVA performed identified statistically significant differences among the datasets. A post-hoc Tukey HSD found statistically significant differences between all three datasets (p < 0.01 for all pairings). The negative values for the CXVE indicates that the mass loss was less that the method could detect. The mean ECDs for the DCM, GXVE, and CXVE materials were 180±130nm, 120±50nm, and 130±80nm, respectively. A 30% reduction in diameter occurred between DCM and GXVE, and the ECDs between the HXLPE materials were similar, indicating the cross-linked materials tended to release smaller particles relative to the DCM. The mean aspect ratio for the DCM, GXVE, and CXVE particles were 1.92±0.90, 2.11±0.87, 1.62±0.52. Conclusion: The reduction in wear rate between DCM and GXVE or CXVE aligns with previous studies and further supports that the highly cross-linked material is more resistant to traditional wear mechanisms. The significant improvement of the CXVE compared to GXVE suggests the chemical cross-linking process creates a more uniform and resilient material. These findings align with previously published data on the mechanical properties of the materials where the CXVE material was shown to outperform GXVE materials. The CXVE also has a smaller aspect ratio compared to the other two materials. In general, higher aspect ratio particles tend to be more bioactive.

I et forsøk på å tiltrekke seg yngre målgrupper har enkelte menigheter i Den Norske Kirke utviklet «pop-gudstjenester». Ved å kombinere tradisjonell liturgi med populærkulturelle referanser som Løvenes konge og Harry Potter, har kirken åpnet opp for nye iscenesettelsestrategier. Denne artikkelen argumenterer for at disse nye «pop-gudstjenestene» ikke bare tiltrekker et større publikum, men også åpner for personlige opplevelser av det guddommelige. Undersøkelsen tar utgangspunkt i tre gudstjenester fra Oslo og Bergen, som alle kombinerer tradisjon og popkultur for å skape nye dramaturgiske uttrykk. Den analytiske tilnærmingen kombinerer teorier fra Kim Skjoldager-Nielsen og Dorthe Jørgensen, for å kartlegge «opplevd metafysikk», og når disse opplevelsene inntreffer. Dette gjøres ved å kartlegge møtet mellom den fysiske iscenesettelsen og deltakernes kognitive prosesser, og hvordan dette møtet åpner for opplevd metafysikk, eller et opplevd møte med det guddommelige. På denne måten bidrar artikkelen med innsikt og et analytisk rammeverk for feltene religion- og teatervitenskap.

Background Childhood overweight and obesity prevalence steeply increased during recent decades, prompting the development of many digital behavioral dietary interventions (DBDIs). However, a coherent overview is lacking, which is crucial for delineating research in this field.Objective This scoping review outlines the landscape of DBDIs for improving dietary behaviors in children and adolescents, including delivery modes, design and development approaches, behavioral theory, and outcomes assessed. Secondary objectives involved examining the integration of behavior change techniques (BCTs) and identifying outcomes favoring DBDIs.Methods Following PRISMA guidelines, PsycInfo, PubMed, and Scopus were systematically searched for evaluated DBDIs. Two reviewers independently screened titles and abstracts; one performed full-text screening. Studies included had a digital component, targeted dietary behavior, focused on children or adolescents, and evaluated effects on behavior change, health, or process evaluation outcomes. One reviewer extracted data, including general information, theoretical underpinning, and outcomes assessed, while BCTs were coded independently by two reviewers. DBDIs were deemed favorable if significant improvements were observed in all outcomes (p ≤ .05).Results From 51 included studies, 41 DBDIs were identified, including app-based (37%), web-based (29%), computer-based (27%), text-message-based (5%), and combined technology tools (2%). Stakeholders were involved in the design of 59% of DBDIs, with 5% using co-design methodologies. Studies evaluated behavior change outcomes (86%), process evaluation outcomes (59%), and health outcomes (20%). DBDIs included an average of 6.2 BCTs, primarily ‘Feedback on behavior’ (56%) and ‘Non-specific reward’ (46%). Among experimental studies, 15% yielded favorable results, 58% mixed results, and 28% no favorable results.Discussion This review outlines the diverse landscape of DBDIs, highlighting various technological delivery modes and outcomes assessed. Methodological variations and limitations challenge consistent effectiveness assessment. Future research should prioritize rigorous study designs to understand efficacy and identify effective BCTs among diverse pediatric populations. Leveraging co-design methods may enhance engagement and effectiveness.

Nature is increasingly recognized for its potential to address societal challenges in cities, through the delivery of ecosystem services (ES). However, large-scale assessments quantifying this potential are rare. In this study, we modelled five ES (local temperature regulation, flood control, global climate regulation, habitat maintenance, and human interaction with nature) across 708 European urban areas. Using a supply-demand approach, we assessed ES delivery: the extent to which ES supply was sufficient to meet the corresponding societal demands. We found that ES delivery varied both spatially and between ES. On average, nearly 50% of the demand was fulfilled, with the highest values for habitat maintenance (81 ± 15%; mean ± SD), flood control (65 ± 13%), and human interaction with nature (59 ± 15%) and much lower values for local temperature regulation (23 ± 28%) and global climate regulation (16 ± 28%). We further found positive pairwise correlations between all ES (Spearman’s ρ from 0.15 to 0.65), with the strongest correlation between habitat maintenance and global climate regulation. Variation in ES delivery across the urban areas was mainly related to differences in the share of green space and the size of the urban areas, whereby ES delivery was positively related to both. Our broad-scale comparative assessment can serve as a starting point for more sophisticated model-based assessments quantifying the full potential of urban nature to meet societal demands across large areas, for example by including a broader set of ES and accounting for city-specific demands.

Objective: Persistent foramen ovale (PFO) is a risk factor for young stroke. Agitated saline serum is used to deliver small gaseous emboli to the brain in transcranial Doppler ultrasound (TCD) for the detection and grading of PFO. In this study we validated a PFO algorithm that can differentiate between gaseous emboli and artifacts. Methods: The validation cohort comprised 18 patients with positive PFO examinations. The PFO algorithm uses a binary tree that separates high-intensity transients signals (HITs) into gaseous emboli or artifacts based on intensity, zero-crossing, and velocity parameters. Results: The cohort exhibited 385 macroscopic gaseous emboli meeting the >3 dB criterion. An additional 137 gaseous emboli were noticed below the 3-dB intensity cutoff value. The low-intensity gaseous emboli included both macroscopic and microscopic air bubbles observed in curtains. Nearly all emboli (98 %) above the 3-dB level showed overt frequency modulation. The overall accuracy of the PFO algorithm in discriminating macroscopic gaseous emboli and artifacts was 96.4 %, with a similar percentage of sensitivity and specificity (96.4 %). The inter-observer agreement of human experts was excellent (ic-CC 0.989 and 0.953). Conclusions: Macroscopic gaseous emboli and artifacts during PFO exams can be accurately discriminated by the PFO algorithm. The PFO algorithm cannot be used as a standalone system as microscopic air bubbles might escape proper identification. This knowledge will be important in the design of future PFO algorithms which should make it possible to classify the PFO grade without the interference of humans.

Increased climate impacts threaten coastal functions globally, highlighting the need for multifunctional coastal climate adaptation. Sand nourishment can adapt sandy coasts to sea level rise, mitigate erosion, increase flood safety, enhance ecological habitats and expand recreational space. Therefore, sand nourishment is increasingly regarded as a promising nature-based strategy for coastal climate adaptation. However, despite this growing recognition, the assessment of how sand nourishment design impacts multifunctional adaptation remains limited. In this perspective article, we argue for three key lessons for researchers to optimise assessing multifunctional coastal climate adaptation by sand nourishment. We conducted stakeholder workshops to scope and inform our perspective, performed semi-structured literature reviews to concretise and validate this for international applications, built a qualitative model to visualise our interdisciplinary overview of how nourishments impact coastal multifunctionality, reflected on this in expert workshops, and identified implications for researchers. In this manner, we assessed the effects of nourishment design on coastal morphology, ecology, socio-economics and ecosystem services in realising the key policy goals of flood safety, nature and recreation. We found that sand nourishment design can result in conflicts between policy goals, generate ambiguous outcomes and lead to system-wide feedback effects. As such, we identified three key lessons: (1) conflicts between policy goals require informing political decision-making on prioritisation between coastal functions, (2) concreteness is needed on otherwise ambiguous functions, and (3) ongoing, multidisciplinary system-wide monitoring is essential. We thus call for a holistic approach to sand nourishment design and encourage researchers from diverse expertise and localities to expand on and adapt our findings to optimise informing sand nourishment design for delivering multifunctional coastal climate adaptation worldwide.

ABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p