Search

Abstract Background Colorectal cancer with liver metastasis affects both men and women. However, therapeutic strategies and long-term outcomes could be influenced by patients’ sex, due to variations in tumour biology, lifestyle, and dietary habits. By conducting a comprehensive comparative analysis, this study aims to detail differences in tumour characteristics, postoperative complications, recurrence rates, and survival outcomes between sexes. Methods Single-centre retrospective analysis between 2010 and 2022 of all patients undergoing liver surgery for colorectal liver metastases (CRLM) at the Department of Surgery, Charité– Universitätsmedizin Berlin. Patients were stratified by sex. Statistical analysis was performed using RV4.2. Results We analysed 642 patients who underwent hepatic resections for CRLM. Baseline patient characteristics were comparable between sexes: However, significant differences (p

Abstract Currently, most research explaining why countries lead or lag in climate policy assumes a problem-oriented perspective, focusing on barriers to climate policy adoption. Here, we argue that correcting for past failures, solving problems, and bringing climate policies back on track for the Paris Agreement requires a solution-oriented perspective on the political enablers of ambitious climate policies. We unite a growing research community that has previously been scattered across disciplinary subfields with various ontological and epistemological assumptions. Rooted in a thematic review of the scientific literature, we introduce a framework with a typology of six political enablers for ambitious climate policy at its core. For each enabler, we summarize key policy implications. We illustrate our framework with a case study on the adoption of emission trading systems in the transport and building sectors in Germany and the European Union (EU) allowing future solution-oriented research to build on our effort.

Abstract Altermagnets are a novel class of magnetic materials, where magnetic order is staggered both in coordinate and momentum space. The metallic rutile oxide RuO2, long believed to be a textbook Pauli paramagnet, recently emerged as a putative workhorse altermagnet when resonant X-ray and neutron scattering studies reported nonzero magnetic moments and long-range collinear order. While some experiments seem consistent with altermagnetism, magnetic order in RuO2 remains controversial. We show that RuO2 is nonmagnetic, both in bulk and thin film. Muon spectroscopy complemented by density-functional theory finds at most 1.14 × 10−4 μ B/Ru in bulk and at most 7.5 × 10−4 μ B/Ru in 11 nm epitaxial films, at our spectrometers’ detection limit, and dramatically smaller than previously reported neutron results that were used to rationalize altermagnetic behavior. Our own neutron diffraction measurements on RuO2 single crystals identify multiple scattering as the source for the false signal in earlier studies.

Abstract Background Multimodal two-stage hepatectomy (mTSH) is used in patients with bilobar colorectal liver metastases (CRLM) that cannot be treated with one surgical procedure due to insufficient future liver remnant. Interval chemotherapy has been proposed to improve disease control in CRLM patients undergoing mTSH. We here present a narrative review of clinical studies on mTSH including the use of interval chemotherapy in patients with CRLM. Methods A systematic literature search of the PubMed databases as well as the ClinicalTrials.gov registry was performed. Results The use of interval chemotherapy during mTSH was reported in 23 studies and applied in 595 out of 1,461 patients with CRLM. Two studies report on the actual effects of this treatment, one study describes a trend towards improved disease progression rate. No serious adverse events caused by interval chemotherapy were observed. There is currently no randomized clinical trial investigating the efficacy and safety of interval chemotherapy during mTSH. Conclusion The currently available data indicate that interval chemotherapy does neither impair liver hypertrophy during mTSH nor cause procedure-associated complications in patients with CRLM. Results from randomized clinical trials on the potential positive effect on disease control are not yet available.

Study region: Ljubljansko polje aquifer in the central part of Slovenia. Study focus: Impeller flowmeter was used together with the water quality probe to determine the flow characteristics of water under ambient conditions (without pumping) in 13 boreholes in a highly productive alluvial aquifer. The study focused on analysing the characteristics and variability of intraborehole flows in relation to the technical features of the boreholes, as well as the geometry and geological composition of the aquifer. New hydrological insights for the region: The study has shown that vertical hydraulic gradients are not limited to complex multiple aquifer systems but can also occur in uniform alluvial aquifers without typical aquitard layers if hydraulic head differences exist between the upper and lower parts of the aquifer. The intraborehole flows are mainly caused by pressure-driven convection in deeper boreholes with long screens. The direction and velocity of these flows are strongly influenced by the morphology of the bedrock. Downward water flows are closely related to the local deepening of the bedrock and upward flows to the local rise of the bedrock. In some boreholes, intraborehole flow rates exceed the typical pumping rates for groundwater sampling, raising concerns about the representativeness of samples collected using conventional sampling methods. Hydrochemical logs proved to be a valuable complementary method to determine the locations of the main inflows.

Abstract Understanding drivers of river mobility—temporal shifts in river channel positions—is critical for managing fluvial landscapes sustainably and for interpreting past river responses to climate change. However, direct observations linking river mobility and water discharge variability are scarce. Here, we pair multi‐annual measurements of daily water discharge and river mobility, estimated from Landsat, for 48 rivers worldwide. We show that, across climates and planforms, river mobility is correlated with water discharge variability over daily, intra‐annual, and inter‐annual timescales. For similar mean discharge, higher discharge variability is associated with up to an order‐of‐magnitude faster floodplain reworking. A random forest regression model indicates that discharge variability is the primary predictor of river mobility, when compared to mean water discharge, sediment concentration, and channel‐bed slope. Our results suggest that enhanced hydro‐climatic extremes could accelerate future river mobility, and that past changes to discharge variability may explain the fabric of fluvial strata.

Background Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate. Cardiogenic shock after out‐of‐hospital cardiac arrest (OHCA) can be due to transient myocardial stunning but also reflect the increasing severity of ongoing heart failure. The Society for Cardiovascular Angiography and Interventions (SCAI) proposed a division of cardiogenic shock into 5 phenotypes, with cardiac arrest being a modifier. The objective was to apply SCAI shock classification to a well‐characterized OHCA population and describe the hemodynamic characteristics and prognostic significance of increasing SCAI classes. Methods and Results This is a post hoc analysis of data from the BOX (Blood Pressure and Oxygenation Targets in Post Resuscitation Care) trial of comatose patients with OHCA. Patients were classified according to SCAI class upon hospital admission. Invasive arterial and pulmonary arterial measurements were obtained the first 72 hours after admission, and perfusion pressure, cardiac index and cardiac power output were calculated. Of 789 patients included, 31.6% were classified as SCAI class B/C, 29.9% as SCAI class D, and 38.5% as SCAI class E. The first recorded perfusion pressure differed between SCAI class B/C, D, and E being lower in higher SCAI classes. The difference was found only at the first measurement. Cardiac index and cardiac power output did not differ at any time point between classes. The 1‐year mortality rate increased with SCAI Class B/C to E (21.3%, 34.3%, and 48.4%, respectively; P

Abstract Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+’s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p

Abstract Background Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. Methods 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. Results Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p

Abstract Individual optical addressing in chains of trapped atomic ions requires the generation of many small, closely spaced beams with low cross-talk. Furthermore, implementing parallel operations necessitates phase, frequency, and amplitude control of each individual beam. Here, we present a scalable method for achieving all of these capabilities using a high-performance integrated photonic chip coupled to a network of optical fibre components. The chip design results in very low cross-talk between neighbouring channels even at the micrometre-scale spacing by implementing a very high refractive index contrast between the channel core and cladding. Furthermore, the photonic chip manufacturing procedure is highly flexible, allowing for the creation of devices with an arbitrary number of channels as well as non-uniform channel spacing at the chip output. We present the system used to integrate the chip within our ion trap apparatus and characterise the performance of the full individual addressing setup using a single trapped ion as a light-field sensor. Our measurements showed intensity cross-talk below ~10–3 across the chip, with minimum observed cross-talk as low as ~10–5.

Abstract Background Liver grafts are frequently declined due to high donor age or age mismatch with the recipient. To improve the outcome of marginal grafts, we aimed to characterize the performance of elderly vs. young liver grafts in a standardized rat model of normothermic ex vivo liver machine perfusion (NMP). Methods Livers from Sprague–Dawley rats aged 3 or 12 months were procured and perfused for 6 h using a rat NMP system or collected as a reference group (n = 6/group). Tissue, bile, and perfusate samples were used for biochemical, and proteomic analyses. Results All livers cleared lactate during perfusion and continued to produce bile after 6 h of perfusion (614 mg/h). Peak urea levels in 12-month-old animals were higher than in younger animals. Arterial and portal venous pressure, bile production and pH did not differ between groups. Proteomic analysis identified a total of 1477 proteins with oxidoreductase and catalytic activity dominating the gene ontology analysis. Proteins such as aldehyde dehydrogenase 1A1 and 2-Hydroxyacid oxidase 2 were significantly more present in livers of older age. Conclusions Young and elderly liver grafts exhibited similar viability during NMP, though proteomic analyses indicated that older grafts are less resilient to oxidative stress. Our study is limited by the elderly animal age, which corresponds to mature but not elderly human age typically seen in marginal human livers. Nevertheless, reducing oxidative stress could be a promising therapeutic target in the future.

Category: Ankle; Trauma Introduction/Purpose: Due to the increasing accessibility of Internet access, it is becoming more and more important to ensure that the informational material available online for patient education is both accurate and readable to promote a greater degree of health literacy. This study sought to investigate the quality and readability of the most popular online resources for ankle fractures. Methods: After conducting a Google search using six terms related to ankle fractures, we collected the first 20 non-sponsored results for each term. Readability was evaluated using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), and Gunning Fog Index (GFI) instruments. Quality was evaluated using an author-created Ankle Fracture Index (AFI). Results: A total of 46 out of 120 articles met the inclusion criteria. The mean FKGL, FRE, and GFI scores were 8.4 ± 0.5, 57.5 ± 3.2, and 10.5 ± 0.5, respectively. The average AFI score was 15.4 ± 1.4, corresponding to an “acceptable” quality rating. Almost 70% of articles (n = 32) were written at or below the recommended eighth grade reading level. Most articles discussed the need for imaging in diagnosis and treatment planning while neglecting to discuss the risks of surgery or potential future operations. Conclusion: Ankle fractures are a common injury among young and old patients alike. With a varied range of treatments available, patients are likely to perform their own Internet searches before arriving at the doctor’s office. Current, online patient education materials on ankle fractures diverge from the overall trend in orthopaedics by demonstrating an eight grade average reading grade level and an acceptable quality on content analysis. Further work should surround increasing information regarding risk factors, complications for surgery, and long-term recovery.

BackgroundSurgery is the preferred treatment for primary hyperparathyroidism. Minimally invasive parathyroidectomy is only feasible with accurate preoperative localisation. Virtual 3D anatomical models can be constructed from patient-specific CT scans using segmentation software.MethodsWe aimed to create virtual 3D models from 4D-CT scans of parathyroid tumours using segmentation technology. We designed a small pilot study to assess the utility of 3D models within surgical practice. We assessed surgeon, trainee and patients’ opinion and satisfaction with the models. The NASA TLX survey was the primary data collection toolResultsCreation of novel 3D models was achieved, these featured a 360-degree axis of rotation and transparency mode to assist in surgical planning. Models were used intraoperatively with the HoloLens 2 headset to locate parathyroid tumours real time before surgery. Total mean workloads for surgery planning when averaged revealed a decrease workload (39.45 vs 27.45) points with adjunctive use of models (p=0.002). Mental demand showed the greatest decrease in mean workload out of all the 6 subscales tested for in the NASA TLX (210.3 vs 136.7) points. Patient satisfaction score was statistically significant for the difference before and after seeing the 3D model regarding anatomical location (p=≤0.001),ConclusionIn this work, we developed patient-specific virtual 3D anatomical models of parathyroid tumours for use in surgery using novel techniques, previously never applied to parathyroidectomy. Our initial success in model construction and subsequent opinion of surgeons, trainees and patients contributes to the developing body of literature in favour of virtual modelling for parathyroidectomy.

The use of evidence-based practices can be regarded as the gold standard in technology-based learning and instruction. A steadily adopted educational practice is technology-mediated non-interactive teaching, in which students generate explanations of the previously learned contents to a fictitious audience by means of technologies (e.g., video, messenger). Although recent laboratory studies documented benefits of non-interactive teaching, field-oriented evidence is scarce. Research is needed to examine how laboratory evidence applies to authentic learning environments with school students and to determine whether these effects are generalizable to different authentic contexts. We applied a ManyClasses study to a) examine the generalizability of technology-based non-interactive teaching and b) explore context-related (domain, school type), demographical-related (age, gender, language), and implementation-related (grading, medium, timing) boundary conditions. In collaboration with teachers, we realized k = 20 different teaching units (each consisting of two lessons) in authentic settings across various school types and domains. Using a within-participants design, school students (N = 191) either taught the previously learned contents by means of technology to a fictitious peer or retrieved the contents in mind after the lesson. Results showed no main effect of non-interactive teaching; but domain and school type moderated the learning activity. The findings indicate that non-interactive teaching is not effective per se, but rather depends on the instructional contexts in which it is implemented. The investigation of the teaching effect with new approaches allows, for the first time, more generalizable conclusions to be drawn about non-interactive teaching with technology for students in authentic settings.

The trend towards equipping buildings with active space cooling technology is expected to continue, due to the warming climate. In addition, the electrification of mobility and industry, and the massive rollout of photovoltaics, may put Austria’s power grids under stress if adequate mechanisms are not implemented in time. This study investigates the magnitudes of the loads induced by this increasing demand for cooling, together with the relief that passive cooling measures can provide. Data from current climate models, measured real load profiles from households, building stock models, and dynamic building simulations are utilised, alongside stakeholder and expert opinions, to fine-tune the analysis. This article suggests plausible scenarios for the development of the demand for cooling energy in Austria until 2050, and analyses the aggregated effect of the different options for cooling on the electricity power grid. The integration of cooling loads is expected to cause overloads or voltage violations only for a few types of grid within the periods investigated here. Subsidy programs in the building sector often do not properly consider cooling demand. Building regulations and subsidies should therefore focus on passive measures, and only when these are not sufficient should measures related to active cooling be implemented.

Abstract Background Patients who have recurrent atrial fibrillation (AF) following redo catheter ablation may eventually be managed with a pace‐and‐ablate approach, involving pacemaker implant followed by atrioventricular nodal ablation (AVNA). We sought to determine which factors would predict subsequent AVNA in patients undergoing redo AF ablation. Methods We analyzed patients undergoing redo AF ablations between 2013 and 2019 at our institution. Follow‐up was censored on December 31, 2021. Patients with no available follow‐up data were excluded. Time‐to‐event analysis with Cox proportional hazard regression was used to compare those who underwent AVNA to those who did not. Results A total of 467 patients were included, of whom 39 (8.4%) underwent AVNA. After multivariable adjustment, female sex (aHR 4.68 [95% CI 2.30–9.50]; p

Abstract Differentiation of stem and progenitor cells is a highly regulated process that involves the coordinated action of multiple layers of regulation. Here we show how the post-transcriptional regulatory layer instructs the level of chromatin regulation via miR-144 and its targets to orchestrate chromatin condensation during erythropoiesis. The loss of miR-144 leads to impaired chromatin condensation during erythrocyte maturation. Among the several targets of miR-144 that influence chromatin organization, the miR-144-dependent regulation of Hmgn2 is conserved from fish to humans. Our genetic probing of the miR-144/Hmgn2 regulatory axis establish that intact miR-144 target sites in the Hmgn2 3’UTR are necessary for the proper maturation of erythrocytes in both zebrafish and human iPSC-derived erythroid cells while loss of Hmgn2 rescues in part the miR-144 null phenotype. Altogether, our results uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.

Abstract Background Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer’s disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid. Methods 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC. Results LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress. Conclusion The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

Hemileia vastatrix coffee leaf rust reduces Mexican coffee production by 51%. We aimed to analyze the size and distribution of H. vastatrix urediniospores among coffee plantations, as well as the morphological structures of the uredinium. In 2015, 65 leaf samples with rust symptoms were collected from 17 coffee cultivars grown at various altitudes (229–1649 m) under different environmental conditions in 14 regions of four Mexican states. A total of 30 spores per sample were measured and grouped using the Ward centroid method, and the group distribution was analyzed. Uredinia morphology was examined via electron microscopy, and the identity of the rust was confirmed. We identified eight significant spore groups. Groups 8h and 3a had the smallest and largest spores, respectively, which were distributed in two and one state, respectively, at different altitudes. The spores in groups 1b–7f were variable within the intermediate size range, and their distribution was at least one group per state under temperate, warm, and humid conditions. The uredinium had double-cell walls in the pedicels and urediniospores, a split septum, spores with hilum and protuberances, and an oval spore shape; anastomosis was detected on vegetative hyphae and haustoria. These findings may reflect gaps in knowledge in the biological cycle of this rust.

Objective The UK Government increasingly emphasises a comprehensive, multi-agency approach to tackling crime. This pilot study explores the feasibility of integrating police data with routine health data to develop a holistic understanding of the predictors of domestic abuse (DA). Approach The study encompasses three work-packages a) coding the narrative data from Domestic Abuse, Stalking and Harassment (DASH) risk assessment report from Public Protection Notifications (PPNs), which are information-sharing documents recording safeguarding concerns and shared with partner agencies b) exploring to identify what works to harmonise different software systems within police data-sharing approach, c) constructing a case study by linking PPN DASH data with routine health and administrative records. These efforts illustrate the potential of national data-sharing initiatives. Results a) Text mining methods successfully identified and coded (with over 95% accuracy) 17 refereed/involved agencies from the PPN DASH data. b) Barriers to data sharing were attributed to a lack of clarity and consensus regarding appropriate information sharing, rather than technical obstacles. This barrier can be overcome by an unambiguous framework, endorsed at an elevated level, highlighting which data should be shared. c) The data-linkage study revealed that victims of DA had prior interactions with healthcare services before their initial PPN, and younger pregnant victims had higher risk of future healthcare emergency visits. Conclusion and Implication Police and health data integration enhances evidence-based prevention and early identification of vulnerable individuals by both law enforcement and public health services.

Charcot neuro-osteoarthropathy (CNO), mainly as a result of diabetic neuropathy, is a complex problem which carries significant morbidity, and is an increasing burden on healthcare as demographics change globally. A multi-disciplinary team (MDT) is necessary to treat the multiple facets of this disease. The multifactorial and non-homogenous nature of this condition and its management, has prevented the development of comprehensive guidelines based on level 1 evidence. Although there is a trend to surgically treat these patients in tertiary centres, the increasing prevalence of CNO necessitates the capability of all units to manage this condition to an extent locally. This article conducted a thorough literature search of Pubmed and Embase from 2003 to 2023 including the following search terms; “Charcot” “neuroarthropathy” “diabetic foot” “management” “surgery” “treatment” “reconstruction”. The results of this review have been summarised and synthesised into an evidence-based algorithm to aid in the surgical decision-making process, and improve the understanding of surgical management by the whole MDT.

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.

Abstract EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases, which may be present in different epidemiological study designs. It then describes key epidemiological concepts relevant for evidence appraisal. This includes brief explanations for measures of association, exposure assessment, statistical inference, systematic error and effect modification. The guidance then describes the concept of external validity and the principles of appraising epidemiological studies. The customisation of the study appraisal process is explained including tailoring of tools for assessing the risk of bias (RoB). Several examples of appraising experimental and observational studies using a RoB tool are annexed to the document to illustrate the application of the approach. The latter part of this guidance focuses on different steps of evidence integration, first within and then across different streams of evidence. With respect to risk characterisation, the guidance considers how evidence from human epidemiological studies can be used in dose–response modelling with several different options being presented. Finally, the guidance addresses the application of uncertainty factors in risk characterisation when using evidence from human epidemiological studies.

In this paper, we present an activity to introduce the idea of public-key cryptography and to make pre-service STEM teachers explore fundamental informatics and mathematical concepts and methods. We follow the Theory of Didactical Situations within the Didactical Engineering methodology (both widely used in mathematics education research) to design and analyse a didactical situation about asymmetric cryptography using graphs. Following the phases of Didactical Engineering, after the preliminary analysis of the content, the constraints and conditions of the teaching context, we conceived and analysed the situation a priori, with a particular focus on the milieu (the set of elements students can interact with) and on the choices for the didactical variables. We discuss their impact on the problem-solving strategies the participants need to elaborate to decrypt an encrypted message. We implemented our situation and collected qualitative data. We then analysed a posteriori the different stategies that participants used. The comparison of the a posteriori analysis with the a priori analysis showed the learning potential of the activity. To elaborate on different problem-solving strategies, the participants need to explore and understand several concepts and methods from mathematics, informatics, and the frontier of the two disciplines, also moving between different semiotic registers.

Abstract Organoid and spheroid technology provide valuable insights into developmental biology and oncology. Optical coherence tomography (OCT) is a label-free technique that has emerged as an excellent tool for monitoring the structure and function of these samples. However, mature organoids are often too opaque for OCT. Access to multi-angle views is highly desirable to overcome this limitation, preferably with non-contact sample handling. To fulfil these requirements, we present an ultrasound-induced reorientation method for multi-angle-OCT, which employs a 3D-printed acoustic trap inserted into an OCT imaging system, to levitate and reorient zebrafish larvae and tumor spheroids in a controlled and reproducible manner. A model-based algorithm was developed for the physically consistent fusion of multi-angle data from a priori unknown angles. We demonstrate enhanced penetration depth in the joint 3D-recovery of reflectivity, attenuation, refractive index, and position registration for zebrafish larvae, creating an enabling tool for future applications in volumetric imaging.

Abstract Background After total knee arthroplasty (TKA), patients have limited knee range of motion (ROM), trophic changes and pain. Cryotherapy and compression are recommended in the literature, but no study has shown that cryotherapy and compression combined leads to better results than cryotherapy alone. The primary objective was to compare knee ROM after 21 days of rehabilitation post-TKA between patients who underwent rehabilitation with compressive cryotherapy with those who had cryotherapy alone. The secondary objectives were to compare other trophic, pain and functional outcomes. Methods Forty patients were randomized into two groups: Standard Cryotherapy (SC = 20, median age 77 years), which applied cold packs along with their rehabilitation; and Compressive Cryotherapy (CC = 20, median age 76 years), which received cold compression. Knee joint’s passive and active ROM (primary outcome) were measured with a goniometer. Knee’s circumference, fluctuation test, pain at rest and during activity, 6-minute walking test (6MWT) and KOOS questionnaire were secondary outcomes. The groups were compared on D1 (baseline) and D21 of rehabilitation. A survival analysis has compared the groups on D1, D8, D15, D21. Results All subjects had a significant improvement in all the parameters on D21 relative to D1 (p

Abstract Atomic monolayers on semiconductor surfaces represent an emerging class of functional quantum materials in the two-dimensional limit — ranging from superconductors and Mott insulators to ferroelectrics and quantum spin Hall insulators. Indenene, a triangular monolayer of indium with a gap of ~ 120 meV is a quantum spin Hall insulator whose micron-scale epitaxial growth on SiC(0001) makes it technologically relevant. However, its suitability for room-temperature spintronics is challenged by the instability of its topological character in air. It is imperative to develop a strategy to protect the topological nature of indenene during ex situ processing and device fabrication. Here we show that intercalation of indenene into epitaxial graphene provides effective protection from the oxidising environment, while preserving an intact topological character. Our approach opens a rich realm of ex situ experimental opportunities, priming monolayer quantum spin Hall insulators for realistic device fabrication and access to topologically protected edge channels.

Background: Two-staged hepatectomy (TSH) including portal vein embolization (PVE) may offer surgical treatment for extensive bilobar colorectal liver metastases (CRLM). This study aimed to investigate the feasibility and outcomes of extended right hepatectomy (ERH) within TSH including PVE for patients with extended CRLM. Methods: We retrospectively collected data of patients who underwent TSH for extended CRLM between 2015 and 2021 at our institution. Clearance of the left liver lobe (clear-up, CU) associated with PVE was followed by ERH. Results: Minimally invasive (n = 12, 46%, MIH) or open hepatectomy (n = 14, 54%, OH) was performed. Postoperative major morbidity and 90-day mortality were 54% and 0%. Three-year overall survival was 95%. Baseline characteristics, postoperative and long-term outcomes were comparable between MIH and OH. However, hospital stay was significantly shorter after MIH (8 vs. 15 days, p = 0.008). Additionally, the need for intraoperative transfusions tended to be lower in the MIH group (17% vs. 50%, p = 0.110). Conclusions: ERH following CU and PVE for extended CRLM is feasible and safe in laparoscopic and open approaches. MIH for ERH may result in shorter postoperative hospital stays. Further high-volume, multicenter studies are required to evaluate the potential superiority of MIH.

Abstract An increasingly globalised world has facilitated the movement of non‐native species (NNS) via the poorly regulated international pet trade. While focus is increasingly being placed on preventative action to combat invasive NNS—often cheaper and less difficult than the management of established populations—successful prevention requires controlling potential pathways and obtaining baseline knowledge of species' availability. Here we performed an in‐depth analysis of the freshwater pet trade as one major vector of NNS, compiling its species inventory and deriving threats of NNS release and establishment in the wild. With Germany as our study region, we surveyed pet stores, websites and the country's largest online classified portal, eBay Kleinanzeigen, recording the taxa encountered. For each species, we determined the likelihood of release based on availability and price (cheaper and/or more readily available species have been shown to be of greater risk), and the likelihood of establishment based on ecological niche breadth and niche overlap with environmental conditions in Germany. The survey revealed 669 species, of which 651 were non‐native to Germany. Looking at release likelihood, more readily available species in pet stores and on websites proved to be cheaper. For websites, there was a significant effect of occurrence status (i.e. released, not released, native) on price, with released and native species being significantly cheaper. Species previously released in Germany and elsewhere demonstrated greater niche breadths and greater niche overlaps between their source regions and Germany; and for species released in Germany, there was a significantly positive relationship between the magnitude of niche overlap and the number of documented occurrences. Finally, we combined our release and establishment likelihood findings under ‘Release Risk’ metrics to highlight the species most worthy of prioritisation. We propose these metrics as proactive methods for screening species in the trade, which can inform future policy direction and intervention. Read the free Plain Language Summary for this article on the Journal blog.

Background: Complex interactions between political economy factors and corporate power are increasingly recognized to prevent transformative policy action on non-communicable disease (NCD) prevention. System science offers promising methods for analysing such causal complexity. This study uses qualitative system dynamics methods to map the political economy of diet-related NCD (DR-NCD) prevention policy-making aiming to better understand the policy inertia observed in this area globally.Methods We interviewed 25 key policy actors. We analysed the interviews using purposive text analysis (PTA). We developed individual then combined casual loop diagrams to generate a shared model representing the DR-NCD prevention policy-making system. Key variables/linkages identified from the literature were also included in the model. We validated the model in several steps including through stakeholder validation interviews.Results We identified several inter-linked feedback processes related to political economy factors that may entrench different forms of corporate power (instrumental, structural, and discursive) in DR-NCD prevention policy-making in South Africa over time. We also identified a number of feedback processes that have the potential to limit corporate power in this setting.Conclusion Using complex system methods can be useful for more deeply understanding DR-NCD policy inertia. It is also useful for identifying potential leverage points within the system which may shift the existing power dynamics to facilitate greater political commitment for healthy, equitable, and sustainable food system transformation.

Abstract Doped Mott insulators are the starting point for interesting physics such as high temperature superconductivity and quantum spin liquids. For multi-band Mott insulators, orbital selective ground states have been envisioned. However, orbital selective metals and Mott insulators have been difficult to realize experimentally. Here we demonstrate by photoemission spectroscopy how Ca2RuO4, upon alkali-metal surface doping, develops a single-band metal skin. Our dynamical mean field theory calculations reveal that homogeneous electron doping of Ca2RuO4 results in a multi-band metal. All together, our results provide evidence for an orbital-selective Mott insulator breakdown, which is unachievable via simple electron doping. Supported by a cluster model and cluster perturbation theory calculations, we demonstrate a type of skin metal-insulator transition induced by surface dopants that orbital-selectively hybridize with the bulk Mott state and in turn produce coherent in-gap states.

Rationale & Objective: Older people with progressive chronic kidney disease (CKD) have complex health care needs. Geriatric evaluation preceding decision making for kidney replacement is recommended in guidelines, but implementation is lacking in routine care. We aimed to evaluate implementation of geriatric assessment in CKD care. Study Design: Mixed methods implementation study. Setting & Participants: Dutch nephrology centers were approached for implementation of geriatric assessment in patients aged ≥70 years and with an estimated glomerular filtration rate of ≤20 mL/min/1.73 m2. Quality Improvement Activities/Exposure: We implemented a consensus-based nephrology-tailored geriatric assessment: a patient questionnaire and professionally administered test set comprising 16 instruments covering functional, cognitive, psychosocial, and somatic domains and patient-reported outcome measures. Outcomes: We aimed for implementation in 10 centers and 200 patients. Implementation was evaluated by (i) perceived enablers and barriers of implementation, including integration in work routines (Normalization Measure Development Tool) and (ii) relevance of the instruments to routine care for the target population. Analytical Approach: Variations in implementation practices were described based on field notes. The postimplementation survey among health care professionals was analyzed descriptively, using an explanatory qualitative approach for open-ended questions. Results: Geriatric assessment was implemented in 10 centers among 191 patients. Survey respondents (n = 71, 88% response rate) identified determinants that facilitated implementation, ie, multidisciplinary collaboration (with geriatricians) -meetings and reports and execution of assessments by nurses. Barriers to implementation were patient illiteracy or language barrier, time constraints, and patient burden. Professionals considered geriatric assessment sufficiently integrated into work routines (mean, 6.7/10 ± 2.0 [SD]) but also subject to improvement. Likewise, the relevance of geriatric assessment for routine care was scored as 7.8/10 ± 1.2. The Clinical Frailty Score and Montreal Cognitive Assessment were perceived as the most relevant instruments. Limitations: Selection bias of interventions’ early adopters may limit generalizability. Conclusions: Geriatric assessment could successfully be integrated in CKD care and was perceived relevant to health care professionals. Plain-Language Summary: The number of older persons with kidney failure is increasing, many of whom have cognitive decline or are dependent on others for daily life tasks. These problems are often overlooked but relevant for future treatment choices, and they affect quality of life. We asked 10 health care centers to use tests and questionnaires to identify these issues, thus being able to offer additional support. We learned that it is possible to use these assessments in practice and that professionals found them relevant. Collaboration with geriatric departments was perceived valuable. However, there are also challenges, such as not having enough time and personnel and burden to patients. Understanding these possibilities and challenges is crucial for improving care for older patients with kidney failure.

Abstract Explaining the spatially variable impacts of flood‐generating mechanisms is a longstanding challenge in hydrology, with increasing and decreasing temporal flood trends often found in close regional proximity. Here, we develop a machine learning‐informed approach to unravel the drivers of seasonal flood magnitude and explain the spatial variability of their effects in a temperate climate. We employ 11 observed meteorological and land cover (LC) time series variables alongside 8 static catchment attributes to model flood magnitude in 1,268 catchments across Great Britain over four decades. We then perform a sensitivity analysis to assess how a 10% increase in precipitation, a 1°C rise in air temperature, or a 10 percentage point increase in urban or forest LC may affect flood magnitude in catchments with varying characteristics. Our simulations show that increasing precipitation and urbanization both tend to amplify flood magnitude significantly more in catchments with high baseflow contribution and low runoff ratio, which tend to have lower values of specific discharge on average. In contrast, rising air temperature (in the absence of changing precipitation) decreases flood magnitudes, with the largest effects in dry catchments with low baseflow index. Afforestation also tends to decrease floods more in catchments with low groundwater contribution, and in dry catchments in the summer. Our approach may be used to further disentangle the joint effects of multiple flood drivers in individual catchments.

Abstract BackgroundThe standard treatment for rectus diastasis is rectus sheath plication during abdominoplasty. Lasting correction of diastasis is essential, but there is currently a debate as to whether absorbable or nonabsorbable rectus plication achieves a lower rate of recurrence. ObjectivesThe goal of this study is to assess long-term patient outcomes and the recurrence of rectus diastasis after plication with long-lasting absorbable sutures. MethodsA retrospective study of abdominoplasties performed by the senior author between 2018 and 2022 was performed. Only female patients with >6 months of follow-up were included. Plication of the rectus muscles was performed with a combination of interrupted, buried, figure of eight #0 polydioxanone suture and running #0 Maxon (Covidien, Mansfield, MA). Outcomes were assessed by physical examination at postoperative visits. A retrospective chart review was used to obtain demographic and perioperative information. ResultsSeventy-one patients underwent abdominoplasty with an average follow-up of 21.1 months. The average age was 43 years, and the average BMI was 27 kg/m2 ConclusionsAbdominal wall plication using a double-layered, long-lasting absorbable suture closure is a safe, reliable, and effective method to address rectus diastasis during abdominoplasty. Our technique achieved no recurrence of diastasis in any patient and a low complication profile. Level of Evidence: 3

Background:. Targeted muscle reinnervation (TMR), a surgical technique developed by the senior authors that coapts proximal ends of nerves to distal motor nerves of adjacent muscles, has demonstrated efficacy in the treatment and prevention of neuroma pain. The objective of this study is to describe the surgical technique for TMR of the superficial peroneal nerve (SPN) and deep peroneal nerve (DPN) in nonamputee patients and provide data on postoperative functional outcomes. Methods:. A single-institution retrospective chart review was performed between March 2018 and April 2021. Patients were de-identified and included if they were nonamputees receiving TMR for pain in the peroneal nerve distribution. Data extracted included demographic information, symptoms before operation, relevant nerve coaptation, peri-, and postoperative complications, and long-term functional outcomes. Results:. Of the 19 patients reviewed, 11 patients underwent TMR of the SPN alone: eight had complete resolution of their symptoms; two indicated partial improvement in pain; and one patient had no improvement. Four patients underwent TMR of the DPN alone: two patients had complete resolution of their pain, and two patients had partial improvement with pain. Four patients underwent TMR of both the SPN/DPN: two patients had complete resolution of their symptoms, and two patients were noted to have significant improvement but had persistent pain from prior foot operations. Average follow-up time was 260 days. Conclusions:. TMR is a successful technique in the management of SPN and DPN neuroma pain. Our technique revealed excellent clinical outcomes, no procedure-specific complications, and improved subjective pain reports.

Abstract As part of the risk assessment (RA) requirements for genetically modified (GM) plants, according to Regulation (EU) No 503/2013 and the EFSA guidance on the RA of food and feed from GM plants (EFSA GMO Panel 2011), applicants need to perform a molecular characterisation of the DNA sequences inserted in the GM plant genome. This Technical Note to the applicants puts together requirements and recommendations for the quality assessment of the methodology, analysis and reporting when DNA sequencing is used for the molecular characterisation of GM plants. In particular, it applies to the use of Sanger sequencing and next‐generation sequencing for the characterisation of the inserted genetic material and its flanking regions at each insertion site, the determination of the copy number of all detectable inserts and the analysis of the genetic stability of the inserts. This updated document replaces the EFSA 2018 Technical Note and reflects the current knowledge in scientific‐technical methods for generating and verifying, in a standardised manner, DNA sequencing data in the context of RA of GM plants. It does not take into consideration the verification and validation of the detection method which remains under the remit of the Joint Research Centre (JRC).

Abstract Introduction Multidisciplinary team meetings (MDMs), also known as tumor conferences, are a cornerstone of cancer treatments. However, barriers such as incomplete patient information or logistical challenges can postpone tumor board decisions and delay patient treatment, potentially affecting clinical outcomes. Therapeutic Assistance and Decision algorithms for hepatobiliary tumor Boards (ADBoard) aims to reduce this delay by providing automated data extraction and high-quality, evidence-based treatment recommendations. Methods and analysis With the help of natural language processing, relevant patient information will be automatically extracted from electronic medical records and used to complete a classic tumor conference protocol. A machine learning model is trained on retrospective MDM data and clinical guidelines to recommend treatment options for patients in our inclusion criteria. Study participants will be randomized to either MDM with ADBoard (Arm A: MDM-AB) or conventional MDM (Arm B: MDM-C). The concordance of recommendations of both groups will be compared using interrater reliability. We hypothesize that the therapy recommendations of ADBoard would be in high agreement with those of the MDM-C, with a Cohen’s kappa value of ≥ 0.75. Furthermore, our secondary hypotheses state that the completeness of patient information presented in MDM is higher when using ADBoard than without, and the explainability of tumor board protocols in MDM-AB is higher compared to MDM-C as measured by the System Causability Scale. Discussion The implementation of ADBoard aims to improve the quality and completeness of the data required for MDM decision-making and to propose therapeutic recommendations that consider current medical evidence and guidelines in a transparent and reproducible manner. Ethics and dissemination The project was approved by the Ethics Committee of the Charité – Universitätsmedizin Berlin. Registration details The study was registered on ClinicalTrials.gov (trial identifying number: NCT05681949; https://clinicaltrials.gov/study/NCT05681949 ) on 12 January 2023.

Le succès d’un artiste dont la notoriété a traversé les frontières nationales puis continentales suscite toujours admiration et respect, réveille un intérêt scientifique. Car, toute particularité artistique qui s’impose dans la durée et marque durablement les esprits sur une large échelle n’est que la résultante d’une démarche réfléchie impliquant de bons choix sous plusieurs aspects, de bonnes stratégies. En outre, connaître le chemin emprunté par un sénior qui est monté très haut demeure le souci d’un junior. Dans la rumba congolaise, Franco Luambo Makiadi a été non seulement auteur-compositeur, chanteur et guitariste-solo mais aussi le chef d’une entreprise musicale qui est demeurée dans le peloton des leaders 33 ans durant. La connaissance de son management pourrait inspirer les managers de tous les secteurs. Après l’article intitulé ‘’Franco Luambo et le management participatif ‘’ paru dans Congo-Afrique n° 562, en février 2022, celui-ci vise à faire connaitre d’autres principes du management participatifs pratiqués par cet artiste pour mieux conduire son groupe OK-Jazz et son entreprise UN-DEUX-TROIS.

Timber–concrete composite (TCC) structural systems are characterized by the combination of timber and concrete, which are connected to transmit shear forces between the two elements. In addition, to achieve an efficient connection, the slip between the two materials should be limited. Therefore, the load-carrying capacity, the stiffness, and the failure mode of TCC connections are important for the behavior of the composite element. This work aims to investigate the influence of test conditions on TCC connections using shear tests to determine the mechanical properties of connections. Therefore, it is essential to understand the influence of the configuration of the specimens (symmetric as push-out tests or asymmetric as inclined tests), the type of interface between the timber and concrete, and the test procedure (static or cyclic load protocol) on the resulting load-carrying capacity, stiffness, and failure modes. This paper reviews experimental tests conducted on TCC shear connection specimens, using various configurations to assess the influence of the test specimen configuration, material interface, and testing protocol on the determination of the mechanical properties.

High-intensity ultrasound (HIU) can modify muscle structure, leading to improvements in tenderness. However, factors such as packing type and muscle complexity may attenuate the acoustic cavitation. In this research, the effect of packing thickness (40.6–70 μm) on the quality of bovine Gluteus medius and Biceps femoris treated with HIU (37 kHz, 90 W/cm2, 40 min) was evaluated. The hardness of G. medius decreased significantly as the thickness of the packing bag decreased. The wide interfibrillar and intermyofibrillar spaces corroborated the tenderizing effect. These effects are related to damage of cell structure and changes in the collagen content (3.37 ± 0.1 µg/mL). In addition, the HIU decrease the variability in the water holding capacity of the muscle produced by the use of low thickness bags during storage. The trained sensory panel described the sonicated samples in 50.8 μm bags as less hard and juicier. Contrarily, in B. femoris no significant effects were reported in the variables evaluated. B. femoris is a white muscle, with a high amount of collagen (3.59 ± 0.1 µg/mL) and little intramuscular fat. Consequently, the effect of the HIU on muscle quality is associated with the composition of the muscle fibers and the thickness of the packing bag. HIU application is recommended to improve the quality of leg muscles whenever low-thickness bags (50.8 μm or less) are used.

Nicotinamide adenine dinucleotide (NAD+), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD+ was primarily considered to be an intracellular molecule (iNAD+), however, its extracellular species (eNAD+) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD+ in bodily fluids such as plasma is paramount to answer important research questions. In order to create a clinically meaningful and reliable quantitation method, we analyzed the relationship of cell lysis, routine clinical laboratory parameters, blood collection techniques, and pre-analytical processing steps with measured plasma eNAD+ concentrations. Initially, NAD+ levels were assessed both intracellularly and extracellularly. Intriguingly, the concentration of eNAD+ in plasma was found to be approximately 500 times lower than iNAD+ in peripheral blood mononuclear cells (0.253 ± 0.02 μM vs. 131.8 ± 27.4 μM, p = 0.007, respectively). This stark contrast suggests that cellular damage or cell lysis could potentially affect the levels of eNAD+ in plasma. However, systemic lactate dehydrogenase in patient plasma, a marker of cell damage, did not significantly correlate with eNAD+ (n = 33; r = −0.397; p = 0.102). Furthermore, eNAD+ was negatively correlated with increasing c-reactive protein (CRP, n = 33; r = −0.451; p = 0.020), while eNAD+ was positively correlated with increasing hemoglobin (n = 33; r = 0.482; p = 0.005). Next, variations in blood drawing, sample handling and pre-analytical processes were examined. Sample storage durations at 4°C (0–120 min), temperature (0° to 25°C), cannula sizes for blood collection and tourniquet times (0 – 120 s) had no statistically significant effect on eNAD+ (p > 0.05). On the other hand, prolonged centrifugation (> 5 min) and a faster braking mode of the centrifuge rotor (< 4 min) resulted in a significant decrease in eNAD+ levels (p

BackgroundConsidering the expected increase in the elderly population and the growing emphasis on aging-related biomedical research, the demand for aged laboratory animals has surged, challenging established husbandry practices. Our objective was to establish a cost-effective method for environmental enrichment, utilizing the liver as a representative organ to assess potential metabolic changes in response to differing enrichment levels.MethodsWe conducted a six-month study involving 24 male Sprague Dawley rats, randomly assigned to four environmental enrichment groups. Two groups were housed in standard cages, while the others were placed in modified rabbit cages. Half of the groups received weekly playtime in an activity focused rat housing unit. We evaluated hormone levels, playtime behavior, and subjective handling experience. Additionally, liver tissue proteomic analysis was performed.ResultsInitial corticosterone levels and those after 3 and 6 months showed no significant differences. Yet, testosterone levels were lower in the control group by the end of the study (p = 0.007). We observed 1871 distinct proteins in liver tissue, with 77% being common across groups. In gene ontology analysis, no specific pathways were overexpressed. In semiquantitative analysis, we observed differences in proteins associated in lipid metabolism such as Apolipoprotein A-I and Acyl-CoA 6-desaturase, which were lower in the control group (p = 0.024 and p = 0.009). Rats in the intervention groups with weekly playtime displayed the least amount of reported distress during inspection or upon room entry and were less prone to accepting treats. Removing animals from their enclosure was most effortless for those in the large cage group. Over time, there was a decrease in conflicts among rats that interacted only twice weekly during playpen time.DiscussionIn summary, refining husbandry practices for aging rats is both simple and budget-friendly, with no apparent adverse effects on stress levels, animal development, or relevant metabolic changes in the liver.

Abstract Subseasonal rainfall forecast skill is critical to support preparedness for hydrometeorological extremes. We assess how a process‐informed evaluation, which subsamples forecasting model members based on their ability to represent potential predictors of rainfall, can improve monthly rainfall forecasts within Central America in the following month, using Costa Rica and Guatemala as test cases. We generate a constrained ensemble mean by subsampling 130 members from five dynamic forecasting models in the C3S multimodel ensemble based on their representation of both (a) zonal wind direction and (b) Pacific and Atlantic sea surface temperatures (SSTs), at the time of initialization. Our results show in multiple months and locations increased mean squared error skill by 0.4 and improved detection rates of rainfall extremes. This method is transferrable to other regions driven by slowly‐changing processes. Process‐informed subsampling is successful because it identifies members that fail to represent the entire rainfall distribution when wind/SST error increases.

Abstract Background The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. Methods Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. Discussion Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.