Biological computations: Limitations of attractor-based formalisms and the need for transients.

Living systems, from single cells to higher vertebrates, receive a continuous stream of non-stationary inputs that they sense, for e.g. via cell surface receptors or sensory organs. By integrating these time-varying, multi-sensory, and often noisy information with memory using complex molecular or neuronal networks, they generate a variety of responses beyond simple stimulus-response association, including avoidance behavior, life-long-learning or social interactions. In a broad sense, these processes can be understood as a type of biological computation. Taking as a basis generic features of biological computations, such as real-time responsiveness or robustness and flexibility of the computation, we highlight the limitations of the current attractor-based framework for understanding computations in biological systems. We argue that frameworks based on transient dynamics away from attractors are better suited for the description of computations performed by neuronal and signaling networks. In particular, we discuss how quasi-stable transient dynamics from ghost states that emerge at criticality have a promising potential for developing an integrated framework of computations, that can help us understand how living system actively process information and learn from their continuously changing environment.

When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.

Obscurin is a giant muscle protein that connects the sarcomere with the sarcoplasmic reticulum, and has poorly understood structural and signalling functions. Increasingly, obscurin variants are implicated in the pathophysiology of cardiovascular diseases. The Arg4344Gln variant (R4344Q) in obscurin domain Ig58, initially discovered in a patient with hypertrophic cardiomyopathy, has been reported to reduce binding to titin domains Z8-Z9, impairing obscurin's Z-disc localization. An R4344Q knock-in mouse developed a cardiomyopathy-like phenotype with abnormal Ca2+-handling and arrhythmias, which were attributed to an enhanced affinity of a putative interaction between obscurin Ig58 and phospholamban (PLN) due to the R4344Q variant. However, the R4344Q variant is found in 15% of African Americans, arguing against its pathogenicity. To resolve this apparent paradox, we quantified the influence of the R4344Q variant (alongside another potentially pathogenic variant: Arg4444Trp (R4444W)) on binding to titin Z8-Z9, novex-3 and PLN using pull-down assays and microscale thermophoresis and characterized the influence on domain stability using differential scanning fluorimetry. We found no changes in titin binding and thermostability for both variants and modestly increased affinities of PLN for R4344Q and R4444W. While we could not confirm the novex-3/obscurin interaction, the PLN/obscurin interaction relies on the transmembrane region of PLN and is not reproducible in mammalian cells, suggesting it is an in vitro artefact. Without clear clinical evidence for disease involvement, we advise against classifying these obscurin variants as pathogenic.

Call, chosen, HA2T2, ANDC: validation of four severity scores in COVID-19 patients.

PURPOSE: To externally validate four previously developed severity scores (i.e., CALL, CHOSEN, HA2T2 and ANDC) in patients with COVID-19 hospitalised in a tertiary care centre in Switzerland. METHODS: This observational analysis included adult patients with a real-time reverse-transcription polymerase chain reaction or rapid-antigen test confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection hospitalised consecutively at the Cantonal Hospital Aarau from February to December 2020. The primary endpoint was all-cause in-hospital mortality. The secondary endpoint was disease progression, defined as needing invasive ventilation, ICU admission or death. RESULTS: From 399 patients (mean age 66.6 years ± 13.4 SD, 68% males), we had complete data for calculating the CALL, CHOSEN, HA2T2 and ANDC scores in 297, 380, 151 and 124 cases, respectively. Odds ratios for all four scores showed significant associations with mortality. The discriminative power of the HA2T2 score was higher compared to CALL, CHOSEN and ANDC scores [area under the curve (AUC) 0.78 vs. 0.65, 0.69 and 0.66, respectively]. Negative predictive values (NPV) for mortality were high, particularly for the CALL score (≥ 6 points: 100%, ≥ 9 points: 95%). For disease progression, discriminative power was lower, with the CHOSEN score showing the best performance (AUC 0.66). CONCLUSION: In this external validation study, the four analysed scores had a lower performance compared to the original cohorts regarding prediction of mortality and disease progression. However, all scores were significantly associated with mortality and the NPV of the CALL and CHOSEN scores in particular allowed reliable identification of patients at low risk, making them suitable for outpatient management.

The Role of Local DFT+U Minima in the First-Principles Modeling of the Metal-Insulator Transition in Vanadium Dioxide.

The DFT+U method is frequently employed to improve the first-principles description of strongly correlated materials. However, it is prone to deliver metastable electronic minima. While these local minima of the DFT+U method are often considered to be computational artifacts, their physical meaning and relationship to true excited states remains unclear. In this work, the possibility of theoretically modeling transformations in the solid state that require thermal or optical excitations of electrons is explored, taking into account the metastable states of the computationally undemanding DFT+U formalism. For this purpose, we choose to examine the example of the VO2 metal-insulator transition. Metastable states that are located on different electronic potential energy surfaces are found to correspond to experimentally observed VO2 phases. The identified metastable electronic states can be used to model the collapse of the VO2 band gap at elevated temperatures and upon photoexcitation as well as other monoclinic-monoclinic phase transformations. The results suggest that local DFT+U minima can indeed carry physical meaning, while they remain under-reported in theoretical literature on transition metal oxides like VO2.

Treatment of grossly dislocated supracondylar humerus fractures after failed closed reduction: a retrospective analysis of different surgical approaches.

INTRODUCTION: The supracondylar humerus fracture (SCHF) is one of the most common pediatric injuries. Highly displaced fractures can be very challenging. If closed reduction fails, the therapy algorithm remains controversial. MATERIALS AND METHODS: In total, 41 patients (21 boys and 20 girls) with irreducible Gartland type III SCHF, treated with open reduction through three different approaches and cross-pin fixation, were retrospectively evaluated. The mean follow-up was 46 months (min.: 12, max.: 83, SD: 23.9). The Mayo elbow performance score (MEPS) as well as the quick disabilities of arm, shoulder and hand (qDASH) score were used to assess the functional outcome. Baumann's angle and the anterior humeral line (AHL, Roger's line) were obtained from follow-up radiographs. Time to surgery, postoperative nerve-palsy, rate of revision surgery, and complication rate were examined. RESULTS: Two revision surgeries were reported. One due to inadequate reduction and one due to secondary loss of reduction. In this context, the AHL was a sufficient tool to detect unsatisfactory reduction. According to the MEPS the functional outcome was excellent (> 90) in 37/41 patients and good (75-89) in 4/41 at the final visit. Fair or poor results were not documented. The qDASH score was 1.8 (min.: 0, max.: 13.6, SD: 3.4). There were no significant differences between the utilized surgical approaches. An iatrogenic injury of the ulnar nerve was not reported in any case. Overall, one heterotopic ossification without impairment of the range of motion and one preliminary affection of the radial nerve were documented. CONCLUSION: In the rare case of an irreducible SCHF, an anatomical reduction can be achieved by open approaches with excellent functional outcome and a high grade of patient satisfaction. All described open approaches can be utilized with a high safety-level.

Gaussian Amplitude Amplification for Quantum Pathfinding.

We study an oracle operation, along with its circuit design, which combined with the Grover diffusion operator boosts the probability of finding the minimum or maximum solutions on a weighted directed graph. We focus on the geometry of sequentially connected bipartite graphs, which naturally gives rise to solution spaces describable by Gaussian distributions. We then demonstrate how an oracle that encodes these distributions can be used to solve for the optimal path via amplitude amplification. And finally, we explore the degree to which this algorithm is capable of solving cases that are generated using randomized weights, as well as a theoretical application for solving the Traveling Salesman problem.

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

OBJECTIVE: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities. BACKGROUND: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative sought to formulate, through rigorous scientific methodology, consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policymakers. METHODS: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across 4 continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in 2 rounds, as well as in a telepresence meeting. RESULTS: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eighty-three of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of 5 other statements. CONCLUSIONS: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic.

Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Triggers and oncologic outcome of salvage radical prostatectomy, salvage radiotherapy and active surveillance after focal therapy of prostate cancer.

PURPOSE: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. METHODS: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan-Meier curves were generated to determine oncological outcomes. RESULTS: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9-16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35-4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. CONCLUSION: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study.

OBJECTIVES: Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing. METHODS: We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses. RESULTS: Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 [interquartile range IQR 1.1-2.3]) vs. 0.8 [IQR 0.7-1.1]) and showed good discrimination (area under the curve 0.78). An increase of 1 nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93 nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, a specificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment. CONCLUSIONS: Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.

Quality of life after hospitalization predicts one-year readmission risk in a large Swiss cohort of medical in-patients.

PURPOSE: Estimating the probability of readmission following hospitalization using prediction scores can be complex. Quality of life (QoL) may provide an easy and effective alternative. METHODS: Secondary analysis of the prospective "TRIAGE" cohort. All medical in-patients admitted to a Swiss tertiary care institution (2016-2019) ≥18 years with a length of stay of ≥2 days (23,309 patients) were included. EQ-5D VAS, EQ-5D index, and Barthel index were assessed at a single telephone interview 30-day after admission. Patients lost to follow-up were excluded. Readmission was defined as a non-elective hospital stay at our institution >24 h within 1 year after discharge and assessed using area under the curve (AUC) analysis with adjustment for confounders. RESULTS: 12,842 patients (43% females, median age 68, IQR 55-78) were included. Unadjusted discrimination was modest at 0.59 (95% CI 0.56-0.62) for EQ-5D VAS. Partially adjusted discrimination (for gender) was identical. Additional adjustment for insurance, Charlson comorbidity index, length of stay, and native language increased the AUC to 0.66 (95% CI 0.63-0.69). Results were robust irrespective of time to event (12, 6 or 3 months). A cut-off in the unadjusted model of EQ-5D VAS of 55 could separate cases with a specificity of 80% and a sensitivity of 30%. CONCLUSION: QoL at day 30 after admission can predict one-year readmission risk with similar precision as more intricate tools. It might help for identification of high-risk patients and the design of tailored prevention strategies.

Three-dimensional motion of the patella in French bulldogs with and without medial patellar luxation.

BACKGROUND: French bulldogs exhibit significantly larger femoral external rotation and abduction than other breeds. We were curious as to whether this peculiar leg kinematic affects patellar motion and/or might induce medial patellar subluxation (MPSL) or medial patellar permanent luxation (MPPL). We hypothesized that the more abducted leg posture during stance causes an unusual medial pull direction of the rectus femoris muscle during stance, and that this may facilitate the occurrence of MPSL or even MPPL during locomotion. To test our hypothesis, we analyzed existing stifle-joint X-ray-sequences collected during the treadmill walk and trot of seven adult female French bulldogs. We estimated 3D-patellar kinematics using Scientific Rotoscoping. RESULTS: The three-dimensional motion of the patella comprises rotations and translations. From the seven dogs analyzed, three exhibited MPSL and one MPPL during the gait cycle. Medial patellar luxation (MPL) occurred mostly around toe-off in both gaits studied. Patellar position was generally not gait-related at the analyzed timepoints. In dogs with MPL, the patella was placed significantly more distally (p = 0.037) at touch-down (TD) and at midswing (p = 0.024), and significantly more medial at midswing (p = 0.045) compared to dogs without MPL. CONCLUSIONS: Medial patellar luxation seems to be the consequence of the far from parasagittal position of the stifle joint during stance due to a broad trunk, and a wide pelvis. This peculiar leg orientation leads to a medial sideway pull caused by the rectus femoris muscle and the quadriceps femoris and may initiate plastic deformation of the growing femur and tibia. Thus, a way to avoid MPL could be to control breeding by selecting dogs with lean bodies and narrow pelvis. Actual breeding control programs based on the orthopedic examination are susceptible to errors. Systematic errors arise from the fact that the grading system is highly dependent on the dog's condition and the veterinarians' ability to perform the palpation on the stifle. Based on our results, the position of the patella at TD, or even perhaps during stand might offer a possibility of an objective radioscopic diagnostic of the MPL.

Density-Based Descriptors of Redox Reactions Involving Transition Metal Compounds as a Reality-Anchored Framework: A Perspective.

Description of redox reactions is critically important for understanding and rational design of materials for electrochemical technologies, including metal-ion batteries, catalytic surfaces, or redox-flow cells. Most of these technologies utilize redox-active transition metal compounds due to their rich chemistry and their beneficial physical and chemical properties for these types of applications. A century since its introduction, the concept of formal oxidation states (FOS) is still widely used for rationalization of the mechanisms of redox reactions, but there exists a well-documented discrepancy between FOS and the electron density-derived charge states of transition metal ions in their bulk and molecular compounds. We summarize our findings and those of others which suggest that density-driven descriptors are, in certain cases, better suited to characterize the mechanism of redox reactions, especially when anion redox is involved, which is the blind spot of the FOS ansatz.

What Are They Worth? Six 30-Day Readmission Risk Scores for Medical Inpatients Externally Validated in a Swiss Cohort.

BACKGROUND: Several clinical risk scores for unplanned 30-day readmission have been published, but there is a lack of external validation and head-to-head comparison. OBJECTIVE: Retrospective replication of six clinical risk scores (LACE, HOSPITAL, SEMI, RRS, PARA, Tsui et al.)f DESIGN: Models were fitted with the original intercept and beta coefficients as reported. Otherwise, a logistic model was refitted (SEMI and Tsui et al). We performed subgroup analyses on main admission specialty. This report adheres to the TRIPOD statement for reporting of prediction models. PARTICIPANTS: We used our prospective cohort of 15,639 medical patients from a Swiss tertiary care institution from 2016 through 2018. MAIN MEASURES: Thirty-day readmission rate and area under the curve (AUC < 0.50 worse than chance, > 0.70 acceptable, > 0.80 excellent) CONCLUSIONS: Among several readmission risk scores, HOSPITAL, PARA, and the score from Tsui et al. showed the best predictive abilities and have high potential to improve patient care. Interventional research is now needed to understand the effects of these scores when used in clinical routine. KEY RESULTS: Among the six risk scores externally validated, calibration of the models was overall poor with overprediction of events, except for the HOSPITAL and the PARA scores. Discriminative abilities (AUC) were as follows: LACE 0.53 (95% CI 0.50-0.56), HOSPITAL 0.73 (95% CI 0.72-0.74), SEMI 0.47 (95% CI 0.46-0.49), RRS 0.64 (95% CI 0.62-0.66), PARA 0.72 (95% CI 0.72-0.74), and the score from Tsui et al. 0.73 (95% CI 0.72-0.75). Performance in subgroups did not differ from the overall performance, except for oncology patients in the PARA score (0.57, 95% CI 0.54-0.60), and nephrology patients in the SEMI index (0.25, 95% CI 0.18-0.31), respectively.

Homo-Oligomerisation in Signal Transduction: Dynamics, Homeostasis, Ultrasensitivity, Bistability.

Homo-oligomerisation of proteins is a ubiquitous phenomenon whose exact role remains unclear in many cases. To identify novel functions, this paper provides an exploration of general dynamical mathematical models of homo-oligomerisation. Simulation and analysis of these models show that homo-oligomerisation on its own allows for a remarkable variety of complex dynamic and steady state regulatory behaviour such as transient overshoots or homeostatic control of monomer concentration. If post-translational modifications are considered, however, conventional mass action kinetics lead to thermodynamic inconsistencies due to asymmetric combinatorial expansion of reaction routes. Introducing a conservation principle to balance rate equations re-establishes thermodynamic consistency. Using such balanced models it is shown that oligomerisation can lead to bistability by enabling pseudo-multisite modification and kinetic pseudo-cooperativity via multi-enzyme regulation, thereby constituting a novel motif for bistable modification reactions. Due to these potential signal processing capabilities, homo-oligomerisation could play far more versatile roles in signal transduction than previously appreciated.

Reply to the 'Comment on "Revisiting π backbonding: the influence of d orbitals on metal-CO bonds and ligand red shifts"' by G. Frenking and S. Pan, Phys. Chem. Chem. Phys., 2019, 22, DOI: 10.1039/C9CP05951B.

We respond to the comment by Pan and Frenking with regard to our investigation on transition and alkaline earth metal d orbital influence on their bonding to carbonyl ligands to clarify misconceptions. We do not consider the points raised in the comment as affecting our conclusions.

Reply to the 'Comment on "Revisiting π backbonding: the influence of d orbitals on metal-CO bonds and ligand red shifts"' by G. Frenking and S. Pan, Phys. Chem. Chem. Phys., 2019, 22, DOI.

We respond to the comment by Pan and Frenking with regard to our investigation on transition and alkaline earth metal d orbital influence on their bonding to carbonyl ligands to clarify misconceptions. We do not consider the points raised in the comment as affecting our conclusions.

The relevance, feasibility and benchmarking of nursing quality indicators: A Delphi study.

AIMS: To identify indicators of nursing care performance by identifying structures, processes, and outcomes that are relevant, feasible and have the potential for benchmarking in Swiss acute hospitals. DESIGN: A modified Delphi-Consensus Technique. METHODS: We examined 19 indicators based on the current evidence and that were pre-selected by nursing scientists. Between August-October 2019, a consortium of experts (representatives of different cantons, hospitals, and healthcare roles in Switzerland) determined the relevance, feasibility, and suitability for benchmarking these indicators in two-round modus of digital survey. Consensus was defined a priori by at least 75% agreement on the highest level of a 3-point Likert-type scale. RESULTS: The response rate was 70.4% in the first and 68.4% in the second round. In round one consensus was reached for three indicators on relevance but for none of the indicators regarding feasibility or potential for benchmarking. For round two, the experts suggested two additional indicators (new total of 21 indicators). Of 21 indicators, consensus was reached on twelve regarding relevance, seven regarding feasibility, and two regarding the potential for benchmarking. CONCLUSION: A national expert consortium defined 12 of 21 nursing care indicators as relevant. Feasibility, however, was estimated only among seven indicators and a consensus on suitability for benchmarking was reached for two nursing-sensitive indicators. IMPACT: The results show how the indicators to evaluate nursing care performance, which have been identified as priority by Canadian nursing scientists, are assessed in a different setting. There are many overlaps, but also some differences in the assessment of the indicators between the different settings. Different health systems prioritize the indicators to evaluate nursing care performance differently, which is why national surveys are important for the compilation of their own (priority) indicator sets.

Association of functional status and hospital-acquired functional decline with 30-day outcomes in medical inpatients: A prospective cohort study.

BACKGROUND: There is growing evidence that patients with functional decline are at increased risk of readmission, mortality and institutionalization. Instruments to measure the status of self-care could provide important information for efficient care planning. The widely used Self Care Index serves as an indicator for the severity of nursing dependency. To date, no evidence is available on the association of the instrument with rehospitalization, mortality and institutionalization. OBJECTIVES: To examine the association of functional status measures (Self Care Index on admission, at discharge and functional decline) with 30-day mortality, readmission and institutionalization in hospitalized non-surgical patients. DESIGN: Prospective cohort study. PARTICIPANTS: We included 4540 emergency medical patients at a single hospital in Switzerland. METHODS: Primary outcome was 30-day mortality rate; secondary outcomes were 30-day readmission and institutionalization. We analyzed the association of the functional status with the binary endpoints using logistic regression models and C-statistics for discrimination. RESULTS: All of the examined measures were significant predictors of overall 30-day mortality; Self Care Index on admission: adj. OR: 0.90 (95% CI: 0.87-0.92); Self Care Index at discharge: adj. OR: 0.86 (95% CI: 0.83-0.88); functional decline: adj. OR: 1.22 (95% CI: 1.14-1.31) and all Self Care Index single items. A combined model (functional status on admission and functional decline during hospitalization) showed a good accuracy with regard to the AUC: adj. AUC: 0.80 (95% CI: 0.74-0.86). CONCLUSIONS: Several functional measures were associated with 30-day mortality. Self Care Index total score, five single items and a combined model showed the best performance.

Field measurements on alluvial watercourses in light of numerical modeling: case studies on the Danube River.

Adequate monitoring and data acquisition of proper hydraulic, sediment, and constituent parameters in alluvial watercourses have become crucial aspects of human interaction with the environment. Conducting well-organized, comprehensive, and meaningful field measurements on natural watercourses are of great importance when assessing its hydraulic, morphological, and ecological state. However, this paper presents a methodology for field measurements on alluvial watercourses in light of numerical modeling. The proposed methodology focuses on collecting field data sets to calibrate numerical models for flow, sediment, and heavy metal transport. The proposed approach targets the simultaneous measurement of hydraulic, sediment transport, and heavy metal transport parameters that are key for calibrating constants and exchange mechanisms in contemporary numerical models. Using the principles laid out in this paper, two sets of measurements were carried out on the Danube River, one on a reach near Mohács in Hungary and the other on a reach near Belgrade in Serbia. The first case study discusses the measurement and results of comprehensive hydraulic and sediment parameters. The second case study considers hydraulic and sediment measurements complemented with trace metal measurements for zinc, lead, and mercury. These measurements were used for calibrating numerical models for flow, sediment, and heavy metal transport, as a proof of concept. It has been demonstrated that the gathered data sets contain key parameters that are strongly linked through physical laws and are needed for calibration purposes, as well as parameters that can allow the newly calibrated coefficients to be confirmed through other measured phenomena. Therefore, the proposed methodology provides minimal data sets with detailed measurements for calibrating numerical models for flow, sediment, and heavy metal transport. Guidelines for future measurements that can suffice the increasing need for numerical modeling and monitoring of natural watercourses are also offered.