Combining machine learning and optimization for the operational patient-bed assignment problem.

Assigning inpatients to hospital beds impacts patient satisfaction and the workload of nurses and doctors. The assignment is subject to unknown inpatient arrivals, in particular for emergency patients. Hospitals, therefore, need to deal with uncertainty on actual bed requirements and potential shortage situations as bed capacities are limited. This paper develops a model and solution approach for solving the patient bed-assignment problem that is based on a machine learning (ML) approach to forecasting emergency patients. First, it contributes by improving the anticipation of emergency patients using ML approaches, incorporating weather data, time and dates, important local and regional events, as well as current and historical occupancy levels. Drawing on real-life data from a large case hospital, we were able to improve forecasting accuracy for emergency inpatient arrivals. We achieved up to 17% better root mean square error (RMSE) when using ML methods compared to a baseline approach relying on averages for historical arrival rates. We further show that the ML methods outperform time series forecasts. Second, we develop a new hyper-heuristic for solving real-life problem instances based on the pilot method and a specialized greedy look-ahead (GLA) heuristic. When applying the hyper-heuristic in test sets we were able to increase the objective function by up to 5.3% in comparison to the benchmark approach in [40]. A benchmark with a Genetic Algorithm shows also the superiority of the hyper-heuristic. Third, the combination of ML for emergency patient admission forecasting with advanced optimization through the hyper-heuristic allowed us to obtain an improvement of up to 3.3% on a real-life problem.

Anxiety in response to the climate and environmental crises: validation of the Hogg Eco-Anxiety Scale in Germany.

Background: As the climate and environmental crises unfold, eco-anxiety, defined as anxiety about the crises' devastating consequences for life on earth, affects mental health worldwide. Despite its importance, research on eco-anxiety is currently limited by a lack of validated assessment instruments available in different languages. Recently, Hogg and colleagues proposed a multidimensional approach to assess eco-anxiety. Here, we aim to translate the original English Hogg Eco-Anxiety Scale (HEAS) into German and to assess its reliability and validity in a German sample. Methods: Following the TRAPD (translation, review, adjudication, pre-test, documentation) approach, we translated the original English scale into German. In total, 486 participants completed the German HEAS. We used Bayesian confirmatory factor analysis (CFA) to assess whether the four-factorial model of the original English version could be replicated in the German sample. Furthermore, associations with a variety of emotional reactions towards the climate crisis, general depression, anxiety, and stress were investigated. Results: The German HEAS was internally consistent (Cronbach's alphas 0.71-0.86) and the Bayesian CFA showed that model fit was best for the four-factorial model, comparable to the factorial structure of the original English scale (affective symptoms, rumination, behavioral symptoms, anxiety about personal impact). Weak to moderate associations were found with negative emotional reactions towards the climate crisis and with general depression, anxiety, and stress. Discussion: Our results support the original four-factorial model of the scale and indicate that the German HEAS is a reliable and valid scale to assess eco-anxiety in German speaking populations.

Evaluating the Public Climate School-A School-Based Programme to Promote Climate Awareness and Action in Students: Protocol of a Cluster-Controlled Pilot Study.

Introduction: School-based programmes may promote knowledge and skills required to address climate change and better health and well-being in adolescents, yet evidence of their effectiveness is limited. In preparation for evaluating the Public Climate School, a school-based intervention to promote climate awareness and action in adolescents, we conduct a pilot study intended to assess procedures for participant recruitment, retention, and data collection, data quality issues and to provide preliminary parameter estimates to guide sample size calculations. Methods and analysis: This unblinded, cluster-controlled pilot study targets students in twelve classes from grades seven to thirteen in German public schools. Seven and five classes were allocated to the intervention and waitlist control arms, respectively. The intervention consisted of (1) live lessons on YouTube, (2) climate-related challenges of the day, (3) workshops and (4) peer exchange sessions. Waitlist control classes participated three weeks later. Measures included the proportion of students completing baseline and follow-up surveys, a comparison of baseline characteristics between students in the retained subsample and those lost to follow-up, proportions of students completing online and paper-pencil-based surveys and problems during data collection based on information reported by teachers. Data quality was assessed as proportions of missing data, associations between missingness and sociodemographic measures using logistic regression models and basic psychometric properties of scales including ceiling effects and internal consistency. Intentions to reduce one's ecological footprint, the primary outcome, and all secondary outcomes for effect estimation were assessed one week pre- and post-intervention from November to December 2021 using items adapted from internationally used instruments and will be investigated using generalised linear mixed models and intention-to-treat analyses. Conclusions: The pilot study will lay the methodological groundwork for a large-scale cluster-randomised effectiveness and process evaluation of the Public Climate School. If proven effective and rolled out more broadly, the Public Climate School has the potential to contribute meaningfully to national climate mitigation and adaptation efforts by reaching a substantial share of adolescents in public schools, including those traditionally less involved in climate action.

Host-guest chemistry of a bidentate silyl-triflate bis-Lewis acid - complex complexation behaviour unravelled by diffusion NMR spectroscopy.

The bidentate silicon-based Lewis acid, bis(dimethyl-(trifluoromethylsulfonyl)silylethyl)dimethylsilane, Me2Si[(CH2)2SiMe2OTf]2, was prepared in a two-step synthesis starting from dimethyldivinylsilane by hydrosilylation with dimethylchlorosilane and subsequent Lewis acidity enhancement of the terminal silicon atoms by substituting the chlorine with triflate groups using silver triflate. The potential of the resulting Me2Si[(CH2)2SiMe2OTf]2 for binding of Lewis basic guests was explored in reactions with mono- and bifunctional aromatic nitrogen bases. A 1 : 2-adduct with pyridine and a 2 : 2-adduct with 4,4'-bipyridine was structurally characterised in the solid state. In solution, diffusion NMR spectroscopy revealed the existence of complex dynamic equilibria of oligomers which are formed by the host with bidentate guests. The size of the oligomers is significantly determined by the spatial arrangement of the docking sites within the guests and depends on the host-guest ratio.

Full Genome Sequence of a Methanomassiliicoccales Representative Enriched from Peat Soil.

The full genome of a Methanomassiliicoccales strain, U3.2.1, was obtained from enrichment cultures of percolation fen peat soil under methanogenic conditions, with methanol and hydrogen as the electron acceptor and donor, respectively. Metagenomic assembly of combined long-read and short-read sequences resulted in a 1.51-Mbp circular genome.

Thirty-Eight-Negative Kinase 1 Is a Mediator of Acute Kidney Injury in Experimental and Clinical Traumatic Hemorrhagic Shock.

Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk for adverse outcome. Recently, thirty-eight-negative kinase 1 (TNK1) was proposed to play a detrimental role in organ damage after trauma/HS. Therefore, we aimed to assess the role of TNK1 in HS-induced kidney injury in a murine and a post hoc analysis of a non-human primate model of HS comparable to the clinical situation. Mice and non-human primates underwent resuscitated HS at 30 mmHg for 60 min. 5 h after the induction of shock, animals were assessed for systemic inflammation and TNK1 expression in the kidney. In vitro, murine distal convoluted tubule cells were stimulated with inflammatory mediators to gain mechanistic insights into the role of TNK1 in kidney dysfunction. In a translational approach, we investigated blood drawn from either healthy volunteers or severely injured patients at different time points after trauma (from arrival at the emergency room and at fixed time intervals until 10 days post injury; identifier: NCT02682550, https://clinicaltrials.gov/ct2/show/NCT02682550). A pronounced inflammatory response, as seen by increased IL-6 plasma levels as well as early signs of AKI, were observed in mice, non-human primates, and humans after trauma/HS. TNK1 was found in the plasma early after trauma-HS in trauma patients. Renal TNK1 expression was significantly increased in mice and non-human primates after HS, and these effects with concomitant induction of apoptosis were blocked by therapeutic inhibition of complement C3 activation in non-human primates. Mechanistically, in vitro data suggested that IL-6 rather than C3 cleavage products induced upregulation of TNK1 and impaired barrier function in renal epithelial cells. In conclusion, these data indicate that C3 inhibition in vivo may inhibit an excessive inflammatory response and mediator release, thereby indirectly neutralizing TNK1 as a potent driver of organ damage. In future studies, we will address the therapeutic potential of direct TNK1 inhibition in the context of severe tissue trauma with different degrees of additional HS.

Functional immune monitoring in severely injured patients-A pilot study.

After severe trauma, the resulting excessive inflammatory response is countered by compensatory anti-inflammatory mechanisms. The systemic inflammatory response to trauma enhanced by inappropriately timed surgical second hits may be detrimental for the patient. On the other hand, overwhelming anti-inflammatory mechanisms may put patients at increased risk from secondary local and systemic infections. The ensuing sepsis and organ dysfunction due to immune dysregulation remain the leading causes of death after injury. To date, there are no clinically applicable techniques to monitor the pro-/anti-inflammatory immune status of the patients and the remaining ability to react to microbial stimuli. Therefore, in the present study, we used a highly standardized and easy-to-use system to draw peripheral whole blood from polytraumatized patients (ISS ≥ 32, n = 7) and to challenge it with bacterial lipopolysaccharide. Secreted cytokines were compared with those in samples from healthy volunteers. We observed a significant decrease in the release of monocyte-derived mediators. Surprisingly, we detected stable or even increased concentrations of cytokines related to T cell maturation and function. For clinical practicability, we reduced the incubation time before supernatants were collected. Even after an abbreviated stimulation period, a stable release of almost all analysed parameters in patient blood could be detected. In conclusion, the data are indicative of a clinically well-applicable approach to monitor the immune status in severely injured patients in a short time. This may be used to optimize the timing of necessary surgical interventions to avoid a boost of proinflammation and reduce risk of secondary infections.

HPV vaccination as preventive approach for recurrent respiratory papillomatosis - a 22-year retrospective clinical analysis.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management focuses on surgical debulking with microdebrider of papillomatous lesions with or without concurrent adjuvant therapy, e.g. Cidofovir®. This retrospective study evaluates the results of patients treated at a department of the university clinic between 1990 and 2012 and compares the results of the conventional treatment with a new treatment approach using adjuvant vaccination with Gardasil®. METHODS: A retrospective Kaplan Maier analysis of n = 24 patients diagnosed and treated with RPR was performed. The records were reviewed for gender, age at the time of first manifestation of disease and time to recurrence. RESULTS: Only n = 2 (15.4%) of the n = 13 vaccinated patients developed a recurrence of the disease after a mean time of 54.9 months (SD: 9.5 months). All patients who were not vaccinated (n = 11; 100%) developed a relapse after a mean time of 12.3 months (SD: 9.72 months). CONCLUSION: We propose that adjuvant HPV vaccination with Gardasil® might have a preventive effect in RRP by occluding new papilloma formation.

Japan's 2014 General Election: Political Bots, Right-Wing Internet Activism, and Prime Minister Shinzo Abe's Hidden Nationalist Agenda.

In this article, we present results on the identification and behavioral analysis of social bots in a sample of 542,584 Tweets, collected before and after Japan's 2014 general election. Typical forms of bot activity include massive Retweeting and repeated posting of (nearly) the same message, sometimes used in combination. We focus on the second method and present (1) a case study on several patterns of bot activity, (2) methodological considerations on the automatic identification of such patterns and the prerequisite near-duplicate detection, and (3) we give qualitative insights into the purposes behind the usage of social/political bots. We argue that it was in the latency of the semi-public sphere of social media-and not in the visible or manifest public sphere (official campaign platform, mass media)-where Shinzo Abe's hidden nationalist agenda interlocked and overlapped with the one propagated by organizations such as Nippon Kaigi and Internet right-wingers (netto uyo) during the election campaign, the latter potentially forming an enormous online support army of Abe's agenda.

MSCA-1/TNAP selection of human jaw periosteal cells improves their mineralization capacity.

Human jaw periosteum-derived cells (JPCs) represent an alternative cell source to bone marrow-derived mesenchymal stem cells for tissue engineering applications in the oral and maxillofacial surgery. In this study we investigated how far the presence or expression of human mesenchymal stem cell antigen-1/tissue non-specific alkaline phosphatase (MSCA-1/TNAP) and LNGFR (CD271) can be utilized to select and enrich the osteogenic progenitor cell fraction from the entire JPC population. Depending on their mineralization capacity, we classified the human isolated JPCs into mineralizing (mJPCs) and non-mineralizing JPCs (nmJPCs). Flow cytometric analyses revealed that undifferentiated mJPCs expressed MSCA-1/TNAP at significant higher levels than nmJPCs at day 5 and 10 of osteogenesis. Western blot analyses showed increased MSCA-1/TNAP expression levels in mJPCs during osteogenesis, whereas in nmJPCs MSCA-1/TNAP expression remained undetectable. Using the MSCA-1 and LNGFR specific antibodies, we separated the positive and negative fractions from the entire mJPC population. In order to analyse the mineralization capacity of the MSCA-1(+) and LNGFR(+) cell subsets, we quantified the calcium deposition in both subpopulations in comparison to the respective negative subpopulations. The MSCA-1(+)/TNAP(+) cell fraction showed a significant higher osteogenic capacity compared to the MSCA-1-/TNAP- cell fraction whereas the LNGFR(+/-) cell fractions did not differ in their osteogenic potential. Our findings suggest that MSCA-1 may represent a promising osteogenic marker for mJPC.

LNGFR induction during osteogenesis of human jaw periosteum-derived cells.

Isolated jaw periosteum-derived cells (JPCs) comprise a morphologically heterogeneous population. There are no known specific surface markers that are able to distinguish between progenitors and cells of other tissue types. The aim of our study was to identify differentiation markers as predictors of JPC mineralization capacity. JPCs underwent osteogenic differentiation after cultivation in osteogenic medium containing known activators. By FACS analysis, we found the low affinity nerve growth factor receptor (LNGFR-CD271) to be induced during the first five days of osteogenesis and that it was expressed at higher levels in mineralizing JPCs (mJPCs) in comparison to non-mineralizing JPCs (nmJPCs). Similar results were obtained by semi-quantitative immunohistochemical stainings and western blot analyses. Quantitative real-time PCR results showed significantly higher LNGFR and alkaline phosphatase transcript levels in mJPCs compared to nmJPCs. LNGFR is a differentiation marker that distinguishes between mineralizing JPCs and non-mineralizing JPCs during the first phase of osteogenesis and can therefore be considered an early surface marker of osteogenic capacity in vitro.