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.

The Clinical Features of Hereditary Alpha-Tryptasemia­Implications for Interdisciplinary Practice.

BACKGROUND: Hereditary alpha-tryptasemia (HAT) is a genetic predisposition of autosomal dominant inheritance that leads to a high normal (≥ 8-11.4 µg/L) or pathologically elevated (>11.4 µg/L) basal serum tryptase (BST) concentration. Its prevalence in the United Kingdom and France is reportedly 5%-6%; its prevalence in Germany is unknown. Symptomatic persons with HAT suffer from a complex constellation of symptoms. As described in this review, HAT is an important differential diagnosis in interdisciplinary practice. METHODS: This review is based on publications about HAT retrieved by a selective search in PubMed, on relevant presentations at scientific meetings, and on our clinical experience. We also collected our own data on the prevalence and clinical manifestations of HAT. RESULTS: According to the literature, HAT is very common among patients in medical centers with BST values of 8 µg/L or above (64-74%). HAT is most commonly associated with neuropsychiatric symptoms such as exhaustion (85%), depressive episodes (59%), sleep disturbances (69%), and memory impairment (59%-68%), followed by gastrointestinal symptoms such as irritable bowel (30%-60%), nausea (51%), and reflux (49%-77%). Typical mast cell-mediated symptoms, such as flushing (47%), itch (69%), urticaria (37%), and anaphylaxis (14%-28%), are reported as well. Less commonly reported are cardiovascular manifestations, such as hypotonia, dizziness, and tachycardia (34%), and joint hypermobility (28%). HAT is more common among patients with sytemic mastocytosis (SM; 12%-21%). It is often associated with severe anaphylaxis induced by insect toxins or unknown triggers. The therapeutic options include treatment with antihistamines, mast-cell stabilizers, or IgE antibodies. CONCLUSION: A diagnosis of hereditary alpha-tryptasemia can be strongly suspected on the basis of thorough history-taking and BST measurement and then confirmed by molecular genetic testing.

New urban habits in Stockholm following COVID-19.

During the COVID-19 pandemic, physical distancing, mobility restrictions and self-isolation measures were implemented around the world as the primary intervention to prevent the virus from spreading. Urban life has undergone sweeping changes, with people using spaces in new ways. Stockholm is a particularly relevant case of this phenomenon since most facilities, such as day care centres and schools, have remained open, in contrast to cities with a broader lockdown. In this study, we use Twitter data and an online map survey to study how COVID-19 restrictions have impacted the use of different locations, services and amenities in Stockholm. First, we compare the spatial distribution of 87,000 geolocated tweets pre-COVID-19 and during the COVID-19 pandemic. Second, we analyse 895 survey responses asking people to identify places they 'still visit', 'use more', 'avoid' and self-report reasons for using locations. The survey provides a nuanced understanding of whether and how restrictions have affected people. Service and seclusion were found to be important; therefore, the accessibility of such amenities was analysed, demonstrating how changes in urban habits are related to conditions of the local environment. We find how different parts of the city show different capacities to accommodate new habits and mitigate the effects of restrictions on people's use of urban spaces. In addition to the immediate relevance to COVID-19, this paper thus contributes to understanding how restrictions on movement and gathering, in any situation, expose more profound urban challenges related to segregation and social inequality.

Prediction of In-Hospital Falls Using NRS, PACD Score and FallRS: A Retrospective Cohort Study.

BACKGROUND: Harmful in-hospital falls with subsequent injuries often cause longer stays and subsequently higher costs. Early identification of fall risk may help in establishing preventive strategies. OBJECTIVE: To assess the predictive ability of different clinical scores including the Post-acute care discharge (PACD) score and nutritional risk screening score (NRS), and to develop a new fall risk score (FallRS). METHODS: A retrospective cohort study of medical in-patients of a Swiss tertiary care hospital from January 2016 to March 2022. We tested the ability of the PACD score, NRS and FallRS to predict a fall by using the area under curve (AUC). Adult patients with a length of stay of ≥ 2 days were eligible. RESULTS: We included 19,270 admissions (43% females; median age, 71) of which 528 admissions (2.74%) had at least one fall during the hospital stay. The AUC varied between 0.61 (95% confidence interval (CI), 0.55-0.66) for the NRS and 0.69 (95% CI, 0.64-0.75) for the PACD score. The combined FallRS score had a slightly better AUC of 0.70 (95% CI, 0.65-0.75) but was more laborious to compute than the two other scores. At a cutoff of 13 points, the FallRS had a specificity of 77% and a sensitivity of 49% in predicting falls. CONCLUSIONS: We found that the scores focusing on different aspects of clinical care predicted the risk of falls with fair accuracy. A reliable score with which to predict falls could help in establishing preventive strategies for reducing in-hospital falls. Whether or not the scores presented have better predictive ability than more specific fall scores do will need to be validated in a prospective study.

Obscurin Rho GEF domains are phosphorylated by MST-family kinases but do not exhibit nucleotide exchange factor activity towards Rho GTPases in vitro.

Obscurin is a giant muscle protein (>800 kDa) featuring multiple signalling domains, including an SH3-DH-PH domain triplet from the Trio-subfamily of guanosine nucleotide exchange factors (GEFs). While previous research suggests that these domains can activate the small GTPases RhoA and RhoQ in cells, in vitro characterization of these interactions using biophysical techniques has been hampered by the intrinsic instability of obscurin GEF domains. To study substrate specificity, mechanism and regulation of obscurin GEF function by individual domains, we successfully optimized recombinant production of obscurin GEF domains and found that MST-family kinases phosphorylate the obscurin DH domain at Thr5798. Despite extensive testing of multiple GEF domain fragments, we did not detect any nucleotide exchange activity in vitro against 9 representative small GTPases. Bioinformatic analyses show that obscurin differs from other Trio-subfamily GEFs in several important aspects. While further research is necessary to evaluate obscurin GEF activity in vivo, our results indicate that obscurin has atypical GEF domains that, if catalytically active at all, are subject to complex regulation.

Changes in injury patterns, injury severity and hospital mortality in motorized vehicle accidents: a retrospective, cross-sectional, multicenter study with 19,225 cases derived from the TraumaRegister DGU®.

PURPOSE: In the last 20 years, the number of fatalities due to road traffic accidents (RTA) in Germany has steadily decreased from 7503 to 2724 per year. Due to legal regulations, educational measures and the continuous development of safety technology the number of severe traumatic injuries and injury patterns are most likely to change. The aim of the study was to analyse severely injured motorcyclists (MC) and car occupants (CO) that were involved in RTAs in the last 15 years and investigate the development and changes of injury patterns, injury severity and hospital mortality. METHODS: We retrospectively evaluated data from the TraumaRegister DGU® (TR-DGU) considering all RTA-related injured MCs and COs (n = 19,225) that were registered in the TR-DGU from 2006 to 2020 with a primary admission to a trauma center with continuous participation (14 of 15 years) in the TR-DGU, an Injury Severity Score (ISS) ≥ 16 and aged between 16 and 79 years. The observation period was divided into three 5-year interval subgroups for further analysis. RESULTS: The mean age increased by 6.9 years and the ratio of severely injured MCs to COs changed from 1:1.92 to 1:1.45. COs were in 65.8% male and more often severely injured in the age groups under 30, while the majority of severely injured MCs were in the age group around 50 years and in 90.1% male. The ISS (- 3.1 points) as well as the mortality of both groups (CO: 14.4% vs. 11.8%; MC: 13.2% vs. 10.2%) steadily decreased over time. Nevertheless, the standardized mortality ratio (SMR) hardly changed and stayed < 1. Regarding the injury patterns, the greatest decline of injuries with AIS 3 + were to the head (CO: - 11.3%; MC: - 7.1%), in addition, a decrease of injuries to extremities (CO: - 1.5%; MC: - 3.3%), to the abdomen (CO: - 2.6%; MC: - 3.6%), to the pelvis in COs (- 4.7%) and to the spine (CO: + 0.1%; MC: - 2.4%) were observed. Thoracic injuries increased in both groups (CO: + 1.6%; MC: + 3.2%) and, furthermore, pelvic injuries in MCs (+ 1.7%). Another finding was the increase of the utilization of whole body CTs from 76.6 to 95.15%. CONCLUSION: The severity of injuries and their incidence, especially head injuries, have decreased over the years and seem to contribute to a decreasing hospital mortality of polytraumatized MCs and COs injured in traffic accidents. Young drivers and an increasing number of seniors are the age groups at risk and require special attention and treatment.

Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.

AIMS: A key event in the regulation of cardiac contraction and relaxation is the phosphorylation of phospholamban (PLN) that relieves the inhibition of the sarco/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). PLN exists in an equilibrium between monomers and pentamers. While only monomers can inhibit SERCA2a by direct interaction, the functional role of pentamers is still unclear. This study investigates the functional consequences of PLN pentamerization. METHODS AND RESULTS: We generated transgenic mouse models expressing either a PLN mutant that cannot form pentamers (TgAFA-PLN) or wild-type PLN (TgPLN) in a PLN-deficient background. TgAFA-PLN hearts demonstrated three-fold stronger phosphorylation of monomeric PLN, accelerated Ca2+ cycling of cardiomyocytes, and enhanced contraction and relaxation of sarcomeres and whole hearts in vivo. All of these effects were observed under baseline conditions and abrogated upon inhibition of protein kinase A (PKA). Mechanistically, far western kinase assays revealed that PLN pentamers are phosphorylated by PKA directly and independent of any subunit exchange for free monomers. In vitro phosphorylation of synthetic PLN demonstrated that pentamers even provide a preferred PKA substrate and compete with monomers for the kinase, thereby reducing monomer phosphorylation and maximizing SERCA2a inhibition. However, ß-adrenergic stimulation induced strong PLN monomer phosphorylation in TgPLN hearts and sharp acceleration of cardiomyocyte Ca2+ cycling and haemodynamic values that now were indistinguishable from TgAFA-PLN and PLN-KO hearts. The pathophysiological relevance of PLN pentamerization was evaluated using transverse aortic constriction (TAC) to induce left ventricular pressure overload. Compared to TgPLN, TgAFA-PLN mice demonstrated reduced survival after TAC, impaired cardiac haemodynamics, failure to respond to adrenergic stimulation, higher heart weight, and increased myocardial fibrosis. CONCLUSIONS: The findings show that PLN pentamerization greatly impacts on SERCA2a activity as it mediates the full range of PLN effects from maximum inhibition to full release of SERCA2a function. This regulation is important for myocardial adaptation to sustained pressure overload.

Prevalence, Risk Factors and Outcomes Associated with Physical Restraint in Acute Medical Inpatients over 4 Years-A Retrospective Cohort Study.

BACKGROUND: Physical restraints are frequently used in acute care hospitals. Their application is associated with negative outcomes, while their intended preventive effect is debated. OBJECTIVES: To determine the prevalence of physical restraints and associated outcomes on medical wards in a tertiary care hospital. METHODS: Retrospective cohort study (January 2018 to December 2021). We included all adult medical in-patients and excluded patients with admission to the intensive care unit, short stays (length of stay (LOS) < 48 h), and patients declining informed consent. RESULTS: Of 11,979 admissions, the prevalence of patients with at least one restraint was 6.4% (n = 772). Sensor mats were used most frequently (73.0%, n = 666), followed by blanket restrictions (14.5%, n = 132), bedrails (8.8%, n = 80) and belts (3.7%, n = 34). On average, restraints were applied 19 h (standard deviation (SD) ± 161) before a fall. Average restraint duration was 42 h (SD ± 57). Patients with a restraint had longer LOS 8 days (IQR 5-14) vs. 5 days (IQR 3-9). Median nurses' time expenditure was 309 h (IQR 242-402) vs. 182 h (IQR 136-243) for non-restrained patients. Patients with restraints fell more often (22.5% vs. 2.7%) and were more likely to die (13.3% vs. 5.1%). These differences persisted after adjusting a regression model for important clinical confounders. We saw a decline in the duration of restraints over the years, but no variation between wards. CONCLUSION: Approximately 6% of medical patients, mostly older and severely ill, were affected by restraint use. For the first time, we report data over 4 years up to ward-level granularity.

Comparison of Cardiovascular Procedure Rates in Patients With Supplementary vs Basic Insurance in Switzerland.

Importance: Switzerland's mandatory health insurance provides universal coverage, but residents can opt for supplementary private insurance for nonessential, nonvital amenities. It is debated whether people with supplementary private insurance receive overtreatment due to financial incentives. Objective: To assess whether incidence rates of cardiovascular procedures in people with supplementary private insurance are higher than in those with basic insurance only. Design, Setting, and Participants: A population-based weighted cohort comparative effectiveness study, using administrative claims data from Switzerland assessing incidence rates (IRs), was conducted in adults undergoing a nonemergency cardiovascular inpatient procedure from January 1, 2012, to December 31, 2020. Analysis included primary or secondary discharge procedure codes for 1 of the following: percutaneous transluminal coronary angioplasty (PTCA), left atrial appendage (LAA) occlusion, patent foramen ovale (PFO) closure, transcatheter aortic valve replacement (TAVR), mitral valve clip implantation, cardiac pacemaker implantation, and atrial fibrillation/atrial flutter ablation. Exposures: Supplementary private health insurance. Main Outcomes and Measures: Incidence rates of cardiovascular procedures between insurance groups calculated by negative binomial regression adjusted by inverse probability weights. Results: Of 590 919 admissions (median age, 68 years; IQR, 57-77 years), 55.5% male, 15.7% non-Swiss nationality), 70.1% had basic insurance only. Independent of insurance status, IR for all cardiovascular procedures steadily increased over the study years. In general, people with supplementary private insurance received cardiovascular procedures more frequently (IR ratio [IRR], 1.11; 99% CI, 1.10-1.11) than people with basic insurance only. There was also an increase for every procedure: PTCA (IRR, 1.12; 99% CI, 1.12-1.13), LAA closure (IRR, 1.15; 99% CI, 1.13-1.16), mitral valve clip implantation (IRR, 1.08; 99% CI, 1.07-1.09), TAVR (IRR, 1.04; 99% CI, 1.03-1.06), PFO closure (IRR, 1.01; 99% CI, 1.00-1.02), pacemaker implantation (IRR, 1.08; 99% CI, 1.07-1.09), and atrial fibrillation/atrial flutter ablation (IRR, 1.12; 99% CI, 1.11-1.12). Sensitivity analyses, including side procedures, stratification by length of stay, and propensity score matching, suggested robustness of the results. Conclusions and Relevance: This study found an association between supplementary private insurance and a higher likelihood of receiving nonemergency cardiovascular procedures. Whether this higher rate of procedures in people with supplementary private insurance is based on clinical reasoning or due to financial incentives warrants further exploration.

Analysis of the primary utilization of videolaryngoscopy in prehospital emergency care in Germany.

BACKGROUND: In 2019, the German prehospital airway management guidelines were published. One of the recommendations was the primary utilization of videolaryngoscopy (VL) for every prehospital endotracheal intubation (phETI). Guideline compliance is extremely important in emergency medicine as non-compliance in the worst-case scenario leads to death. The study aims to quantify guideline compliance among emergency medical service (EMS) physicians and, subsequently to analyze subgroups influencing compliance. MATERIAL AND METHODS: An online survey was developed and distributed as a hyperlink via email to all medical directors of EMS (n = 155) and the three main operators of helicopter emergency medical services (HEMS) in Germany. The survey was online from August 1st 2021 until October 3rd 2021. The primary outcome measure was the primary VL utilization. Data were evaluated descriptively. A multivariate regression analysis was used to determine associations between the primary VL utilization and age, sex, educational level, specialization, phETI per year, operating field, VL device type, and guideline knowledge. RESULTS: The analysis included 698 EMS physicians. More than 55% of the EMS physicians do not primarily use a videolaryngoscope for phETI. Multivariate regression analysis showed a significantly higher compliance if the devices C­MAC® or McGrath® were on board, guidelines were known or EMS physicians were female. Age, educational level, specialization or prehospital intubation experience had no significant impact. CONCLUSION: The study shows non-compliance with prehospital airway management guidelines in Germany. The guideline recommendation is based on scientific evidence but is not yet generally accepted by all EMS physicians. Videolaryngoscope device type and sex seem to influence the primary VL utilization. Training for EMS physicians must be extended and individual prehospital airway management should be reconsidered by every EMS physician.

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial.

Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial. Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity. Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022. Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning. Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals. Results: There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time. Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge. Trial Registration: isrctn.org Identifier: ISRCTN83274049.

Association of Different Malnutrition Parameters and Clinical Outcomes among COVID-19 Patients: An Observational Study.

Background: Malnutrition is highly prevalent in medical inpatients and may also negatively influence clinical outcomes of patients hospitalized with COVID-19. We analyzed the prognostic implication of different malnutrition parameters with respect to adverse clinical outcomes in patients hospitalized with COVID-19. Methods: In this observational study, consecutively hospitalized adult patients with confirmed COVID-19 at the Cantonal Hospital Aarau (Switzerland) were included between February and December 2020. The association between Nutritional Risk Screening 2002 (NRS 2002) on admission, body mass index, and admission albumin levels with in-hospital mortality and secondary endpoints was studied by using multivariable regression analyses. Results: Our analysis included 305 patients (median age of 66 years, 66.6% male) with a median NRS 2002-score of 2.0 (IQR 1.0, 3.0) points. Overall, 44 patients (14.4%) died during hospitalization. A step-wise increase in mortality risk with a higher nutritional risk was observed. When compared to patients with no risk for malnutrition (NRS 2002 < 3 points), patients with a moderate (NRS 2002 3−4 points) or high risk for malnutrition (NRS 2002 ≥ 5 points) had a two-fold and five-fold increase in risk, respectively (10.5% vs. 22.7% vs. 50.0%, p < 0.001). The increased risk for mortality was also confirmed in a regression analysis adjusted for gender, age, and comorbidities (odds ratio for high risk for malnutrition 4.68, 95% CI 1.18 to 18.64, p = 0.029 compared to patients with no risk for malnutrition). Conclusions: In patients with COVID-19, the risk for malnutrition was a risk factor for in-hospital mortality. Future studies should investigate the role of nutritional treatment in this patient population.

[Interprofessional Training for Discharge Planning: Effects of Self-Efficacy in Nursing and Medical Students]. / Interprofessionelle Schulung für die Spital-Austrittsplanung: Effekte der Selbstwirksamkeit bei Pflege- und Medizinstudierenden.

Interprofessional Training for Discharge Planning: Effects of Self-Efficacy in Nursing and Medical Students Abstract. Concordant and methodical briefing about a patient's disposition for discharge from hospital within the interprofessional ward round can facilitate a timely discharge. However, interprofessional ward rounds require not only professional skills but also knowledge of interprofessional cooperation between all the occupational groups involved. The question arose whether students of the various professions could learn the necessary competencies during their studies. To this end, a training course on interprofessional discharge planning was developed for nursing and medical students. The training includes four phases consisting of flipped classroom and interprofessional skills training. After each phase, a questionnaire was distributed to assess the self-efficacy of participating nursing and medical students regarding their interprofessional collaboration skills. The results showed that self-efficacy increased steadily with increasing study duration from phase 1 to 4. The study also shows that despite the differences between nursing and medical school curricula, students' self-efficacy regarding interprofessional collaboration skills increased during the IAVI training, which strongly suggests that they benefited from the training.

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.

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.

The Origin of the Thermochromic Property Changes in Doped Vanadium Dioxide.

Vanadium dioxide is a promising material for novel smart window applications due to its reversible metal-insulator transition which is accompanied by a change in its optical properties. The transition temperature (TMIT) can be controlled via elemental doping, but the reduction of TMIT is generally coupled with a decrease of the optical contrast between the two phases. To better understand how the contrast is fundamentally connected to TMIT, the thermochromic properties of doped VO2 were theoretically investigated across the metal-insulator transition from first principles. Different dopants and their interaction with the VO2 host structure as well as different modes of doping were studied in detail. It was found that the transition temperature change is mainly related to the stabilization of the high-temperature metallic phase due to lattice deformations which are caused by the presence of the dopant ion. Inherent limitations to the thermochromic performance of VO2 substitutionally doped by the replacement of vanadium cations with other species were found, and alternative approaches were proposed. Specifically, a charge-neutral substitution of oxygen or an oxygen substitution in combination with interstitial doping without net charge transfer between the dopant atoms and VO2 were identified as promising avenues to ensure a low TMIT and no loss of optical contrast in vanadia-based smart window materials.

Prevalence of Micronutrient Deficiencies in Patients Hospitalized with COVID-19: An Observational Cohort Study.

BACKGROUND: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. METHODS: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. RESULTS: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05-0.69, p = 0.01), zinc (0.73, 95% CI 0.55-0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78-0.98, p = 0.02). CONCLUSIONS: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

Understanding physician's knowledge and perception of chronic cough in Switzerland.

BACKGROUND: Cough is one of the most common health issues for which medical attention is sought. A chronic cough (CC) is understood as a cough that lasts longer than 8 weeks. CC encompasses two subsets referred to as refractory chronic cough (RCC) and unexplained chronic cough (UCC). This study aims to assess the current understanding and perceptions of a RCC and UCC, from a physician's perspective in Switzerland and how this understanding and practical work leads to the relevant diagnosis and treatment. METHODS: In October 2020, 549 GPs and 338 pulmonologists in Switzerland, received an invite to participate in the online-based quantitative survey. Data collection was carried out through a 25-minute online survey. The questionnaire was based on structured questions, and conducted on a randomized sample of doctors (general practitioners -GPs and pulmonologists) in the German- and French-speaking part of Switzerland. RESULTS: Overall, 33 pulmonologists and 52 GPs participated in the online survey. Only 39% of GPs, but 73% of pulmonologists, defined chronic cough as a cough lasting 8 weeks or longer. The majority of physicians (72%), especially pulmonologists (88%), perceived a clinical gap regarding the treatment of persistent cough. 74% of the sampled physicians agreed that persistent cough is a high burden of disease for patients. Based on the answers, the annual number of new patients with RCC and UCC in Switzerland is estimated at 9322 patients. CONCLUSIONS: Results of this study have highlighted differences in the terminology used to describe CC (RCC and UCC), in the diagnostic tests used and, in the treatments used between GPs and pulmonologists. These findings suggest the need to align the current language regarding the disease to facilitate a standardized approach for diagnosis and treatment and towards improving patient care and reduce burden of disease for CC (RCC and UCC) patients.

Derivation and validation of a prediction model to establish nursing-sensitive quality benchmarks in medical inpatients: a secondary data analysis of a prospective cohort study.

BACKGROUND: Hospitals are using nursing-sensitive outcomes (NSOs) based on administrative data to measure and benchmark quality of nursing care in acute care wards. In order to facilitate comparisons between different hospitals and wards with heterogeneous patient populations, proper adjustment procedures are required. In this article, we first identify predictors for common NSOs in acute medical care of adult patients based on administrative data. We then develop and cross-validate an NSO-oriented prediction model. METHODS: We used administrative data from seven hospitals in Switzerland to derive prediction models for each of the following NSO: hospital-acquired pressure ulcer (≥ stage II), hospital-acquired urinary tract infection, non-ventilator hospital-acquired pneumonia and in-hospital mortality. We used a split dataset approach by performing a random 80:20 split of the data into a training set and a test set. We assessed discrimination of the models by area under the receiver operating characteristic curves. Finally, we used the validated models to establish a benchmark between the participating hospitals. RESULTS: We considered 36,149 hospitalisations, of which 51.9% were male patients with a median age of 73 years (with an interquartile range of 59-82). Age and length of hospital stay were independently associated with all four NSOs. The derivation and validation models showed a good discrimination in the training (AUC range: 0.75-0.84) and in the test dataset (AUC range: 0.77-0.81), respectively. Variation among different hospitals was relevant considering the risk for hospital-acquired pressure ulcer (≥ stage II) (adjusted Odds ratio [aOR] range: 0.51 [95% CI: 0.38-0.69] - 1.65 [95% CI: 1.33-2.04]), the risk for hospital-acquired urinary tract infection (aOR range: 0.46 [95% CI: 0.36-0.58] - 1.45 [95% CI: 1.31-1.62]), the risk for non-ventilator hospital-acquired pneumonia (aOR range: 0.28 [95% CI: 0.09-0.89] - 2.87 [95% CI: 2.27-3.64]), and the risk for in-hospital mortality (aOR range: 0.45 [95% CI: 0.36-0.56] - 1.39 [95% CI: 1.23-1.60]). CONCLUSION: The application of risk adjustment when comparing nursing care quality is crucial and enables a more objective assessment across hospitals or wards with heterogeneous patient populations. This approach has potential to establish a set of benchmarks that could allow comparison of outcomes and quality of nursing care between different hospitals and wards.

Analysis of Gum proteins involved in xanthan biosynthesis throughout multiple cell fractions in a "single-tube".

Xanthomonas is a phytopathogenic bacterium and of industrial interest due to its capability to produce xanthan, used as a thickener and emulsifier in the food and non-food industry. Until now, proteome analyses of Xcc lacking a detailed view on the proteins involved in xanthan biosynthesis. The proteins involved in the biosynthesis of this polysaccharide are located near, in or at the cell membrane. This study aims to establish a robust and rapid protocol for a comprehensive proteome analysis of Xcc strains, without the need to isolate different cell fractions. Therefore, a method for the analysis of the whole cell proteome was compared to the isolation of specific fractions regarding the total number of identified proteins, the overlap, and the differences between the approaches. The whole cell proteome analysis with extended peptide separation methods resulted in more than 3254 identified proteins covering 73.1% of the whole proteome. The protocol was used to study xanthan production in a label-free quantification approach. Expression profiles of 8 Gum proteins were compared between the stationary and logarithmic growth phase. Differential expression levels within the operon structure indicate a complex regulatory mechanism for xanthan biosynthesis. Data are available via ProteomeXchange with identifier PXD027261. SIGNIFICANCE: Bacteria are metabolite factories with a wide variety of natural products. Thus, proteome analyses play a crucial role to understand the biological processes within a cell behind the biosynthesis of those metabolites. Proteins involved in the biosynthesis of secreted products are often organised on, in or around the membrane allowing metabolite channelling. Experiments targeting those biosynthesis pathways on protein level often require the analysis of multiple cell fractions like cytosolic, inner, and outer membrane. This is time consuming and demands different protocols. The protocol presented here is a rapid and robust solution to study biosynthetic pathways of biological or biotechnological interest in a single approach on protein level, where gene products are partitioned across multiple cell fractions. The use of a single method also simplifies the comparison of different experiments, for example, production vs. nonproduction conditions.