Research Group Helmut Küchenhoff

Large ensembles of climate models are indispensable for analyzing natural climate variability and estimating the occurrence of rare extreme events. Many hydrometeorological applications—such as compound event analysis, return period estimation, weather forecasting, downscaling, and bias correction—rely on an accurate representation of the multivariate distribution of climate variables. However, at high temporal resolutions, variables like precipitation often exhibit significant zero-inflation and heavy-tailed distributions. This inflation propagates through the entire multivariate dependence structure, complicating the relationships between zero-inflated and non-inflated variables. Inadequate modeling and correction of these dependencies can substantially degrade the reliability of hydrometeorological methodologes.
In an earlier work, we developed a novel multivariate density decomposition for zero inflated variables based on vine copulas. This method has been integrated into multivariate Vine Copula Bias Correction for partially zero-inflated margins (VBC), with potential applications in other fields facing high-resolution climate data challenges. We resume the idea behind VBC and illustrate it’s advantages to other bias correction methods. This highlights the interpretability and the advantages of control and assessment of the results generated by VBC.

Loss of kidney function is a substantial personal and public health burden. Kidney function is typically assessed as estimated glomerular filtration rate (eGFR) based on serum creatinine. UK Biobank provides serum creatinine measurements from study center assessments (SC, n = 425,147 baseline, n = 15,314 with follow-up) and emerging electronic Medical Records (eMR, ‘GP-clinical’) present a promising resource to augment this data longitudinally. However, it is unclear whether eMR-based and SC-based creatinine values can be used jointly for research on eGFR decline. When comparing eMR-based with SC-based creatinine by calendar year (n = 70,231), we found a year-specific multiplicative bias for eMR-based creatinine that decreased over time (factor 0.84 for 2007, 0.97 for 2013). Deriving eGFR based on SC- and bias-corrected eMR-creatinine yielded 454,907 individuals with ≥ 1eGFR assessment (2,102,174 assessments). This included 206,063 individuals with ≥ 2 assessments over up to 60.2 years (median 6.00 assessments, median time = 8.7 years), where we also obtained eMR-based information on kidney disease or renal replacement therapy. We found an annual eGFR decline of 0.11 (95%-CI = 0.10–0.12) versus 1.04 mL/min/1.73m2/year (9%-CI = 1.03–1.05) without and with bias-correction, the latter being in line with literature. In summary, our bias-corrected eMR-based creatinine values enabled a 4-fold increased number of eGFR assessments in UK Biobank suitable for kidney function research.

Clinical theories suggest that trauma-focused interventions reduce intrusive memories while preserving voluntary recall. However, concerns persist that they may inadvertently compromise factual memory content. To test these contrasting predictions, we examined the effects of Eye Movement Desensitization and Reprocessing (EMDR), Imagery Rescripting (ImRs), Imaginal Exposure (IE), on involuntary and voluntary memories of an aversive autobiographical event. Healthy participants (N = 182), recruited between 2021 and 2023, completed a free recall task before receiving either one of the interventions or no intervention (NIC). One week later, the recall task was repeated. Intrusion load and frequency were assessed with an app-diary; psychophysiological responses to intrusions were assessed in a laboratory task. Independent raters evaluated disorganization, coherence, consistency of voluntary memory. All interventions reduced intrusion load, but only ImRs decreased intrusion frequency compared to NIC. Psychophysiological responses to intrusions showed no group differences. IE improved the structural organization of voluntary memory by reducing disorganized thoughts, while EMDR and ImRs enhanced conceptual organization by increasing contextual coherence. None of the interventions impaired memory consistency, with no group differences in contradictions or omissions. These findings suggest that these interventions reduce distressing intrusions without compromising voluntary memory. Further research should replicate these effects in clinical samples.

Climate model large ensembles are an essential research tool for analysing and quantifying natural climate variability and providing robust information for rare extreme events. The models simulated representations of reality are susceptible to bias due to incomplete understanding of physical processes. This paper aims to correct the bias of five climate variables from the CRCM5 Large Ensemble over Central Europe at a 3-hourly temporal resolution. At this high temporal resolution, two variables, precipitation and radiation, exhibit a high share of zero inflation. We propose a novel bias-correction method, VBC (Vine copula bias correction), that models and transfers multivariate dependence structures for zero-inflated margins in the data from its error-prone model domain to a reference domain. VBC estimates the model and reference distribution using vine copulas and corrects the model distribution via (inverse) Rosenblatt transformation. To deal with the variables’ zero-inflated nature, we develop a new vine density decomposition that accommodates such variables and employs an adequately randomized version of the Rosenblatt transform. This novel approach allows for more accurate modelling of multivariate zero-inflated climate data. Compared with state-of-the-art correction methods, VBC is generally the best-performing correction and the most accurate method for correcting zero-inflated events.

This study analyzes immune responses to SARS-CoV-2 vaccination and infection, including asymptomatic cases, focusing on infection risks during the Omicron wave, particularly among high-risk healthcare workers. In the KoCo-Impf study, we monitored 6088 vaccinated participants in Munich aged 18 and above. From 13 May to 31 July 2022, 2351 participants were follow-uped. Logistic regression models evaluated primary, secondary, and breakthrough infections (BTIs). Roche Elecsys® Anti-SARS-CoV-2 assays detected prior infections (via anti-Nucleocapsid antibodies) and assessed vaccination/infection impact (via anti-Spike antibodies) using dried blood spots. Our findings revealed an anti-Nucleocapsid seroprevalence of 44.1%. BTIs occurred in 38.8% of participants, with reinfections in 48.0%. Follow-up participation was inversely associated with current smoking and non-vaccination, while significantly increasing with age and receipt of three vaccine doses. Larger household sizes and younger age increased infection risks, whereas multiple vaccinations and older age reduced them. Household size and specific institutional subgroups were risk factors for BTIs. The anti-Nucleocapsid value prior to the second infection was significantly associated with reinfection risk. Institutional subgroups influenced all models, underscoring the importance of tailored outbreak responses. The KoCo-Impf study underscores the importance of vaccination, demographic factors, and institutional settings in understanding SARS-CoV-2 infection risks during the Omicron wave.

Understanding how assignments of instances to clusters can be attributed to the features can be vital in many applications. However, research to provide such feature attributions has been limited. Clustering algorithms with built-in explanations are scarce. Common algorithm-agnostic approaches involve dimension reduction and subsequent visualization, which transforms the original features used to cluster the data; or training a supervised learning classifier on the found cluster labels, which adds additional and intractable complexity. We present FACT (feature attributions for clustering), an algorithm-agnostic framework that preserves the integrity of the data and does not introduce additional models. As the defining characteristic of FACT, we introduce a set of work stages: sampling, intervention, reassignment, and aggregation. Furthermore, we propose two novel FACT methods: SMART (scoring metric after permutation) measures changes in cluster assignments by custom scoring functions after permuting selected features; IDEA (isolated effect on assignment) indicates local and global changes in cluster assignments after making uniform changes to selected features.

Piecewise Exponential Additive Mixed Models (PAMMs) (Bender et al., 2018) have gained popularity in various domains due to their ability to tackle a wide variety of survival problems and their flexibility to model non-linear covariate effects, including time-varying effects and cumulative effects (Bender et al., 2019). One advantage of such reduction techniques is that they do not require any specialised software for the estimation of the model parameters. Thus, in the case of the PAMM, they can be conveniently estimated using generalized additive mixed modeling methodology or, for example, respective boosting or deep learning based approaches (Bender et al., 2022). Nevertheless, their use in practice requires pre-processing, which differs depending on the survival task at hand (e.g. left-truncation, competing risks, etc.) and post-processing (e.g. transforming estimated parameters to useful quantities like survival or transition probabilities). The R package pammtools facilitates the entire modeling process, so far, however, only for single-event data. Here we extend the framework and package capabilities to handle general multi-state models.

The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients.

Data-based methods and statistical models are given special attention to the study of sports injuries to gain in-depth understanding of its risk factors and mechanisms. The objective of this work is to evaluate the use of shared frailty Cox models for the prediction of occurring sports injuries, and to compare their performance with different sets of variables selected by several regularized variable selection approaches. The study is motivated by specific characteristics commonly found for sports injury data, that usually include reduced sample size and even fewer number of injuries, coupled with a large number of potentially influential variables. Hence, we conduct a simulation study to address these statistical challenges and to explore regularized Cox model strategies together with shared frailty models in different controlled situations. We show that predictive performance greatly improves as more player observations are available. Methods that result in sparse models and favour interpretability, e.g. Best Subset Selection and Boosting, are preferred when the sample size is small. We include a real case study of injuries of female football players of a Spanish football club.

Hintergrund: Für Deutschland ist der Langzeitverlauf des Schutzes durch eine Impfstoff-induzierte oder hybride Immunität vor schweren COVID-19-Verläufen unklar. Methode: Wir untersuchten 146.457 geimpfte und zwischen Februar 2022 und Januar 2023 positiv auf SARS-CoV-2- getestete Personen im Alter von 60 bis 99 Jahren aus Bayern. Berechnet wurden adjustierte Hazard Ratios (aHR) für einen schweren Verlauf (COVID-19-bedingte Hospitalisierung oder Tod) in Abhängigkeit vom zeitlichen Abstand zwischen dem Eintritt einer vollständigen oder geboosterten Immunität und dem Infektionsdatum. Ergebnisse: Es wurden 3.342 (2,3%) schwere COVID-19-Verläufe innerhalb der ersten 60 Tage nach der Infektion beobachtet. Das Risiko eines schweren Verlaufs stieg mit zunehmendem Abstand zwischen dem Eintritt des Immunschutzes und der Infektion schrittweise an (aHR [95-%-Konfidenzintervall] nach 6, 9, 12 beziehungsweise 15 Monaten: 1,14 [1,08; 1,20]; 1,33 [1,24; 1,42]; 1,39 [1,25; 1,54]; 1,61 [1,35; 1,93]). Das Risiko stieg langsamer an, wenn ausschließlich mRNA-basierte Impfstoffe zur Anwendung gekommen waren. Wir haben in einer Vorgängerstudie eine anfängliche Wirksamkeit von 82% bei geboosterten (verglichen mit ungeimpften) Fälle ≥ 60 Jahre und eine absolute Risikoreduktion von 2,1% beobachtet. Überträgt man diese Ergebnisse auf unsere aktuelle Studie, so beträgt die verbleibende Wirksamkeit beziehungsweise die absolute Risikoreduktion nach sechs Monaten etwa 71% beziehungsweise 1,8% und nach 15 Monaten 32% beziehungsweise 0,8%. Schlussfolgerung: Diese Ergebnisse deuten darauf hin, dass während der Omikron-Welle der Schutz vor einem schweren COVID-19-Verlauf bei älteren Personen ab dem sechsten Monat nach Impfung graduell nachließ. Limitierungen sind nicht berücksichtigte Störfaktoren, eine mögliche Fehlklassifikation der Todesursache sowie ein Selektionsbias aufgrund fehlender Informationen über Impfstatus und schwere COVID-19-Verläufe.

Hintergrund: Für Deutschland ist der Langzeitverlauf des Schutzes durch eine Impfstoff-induzierte oder hybride Immunität vor schweren COVID-19-Verläufen unklar. Methode: Wir untersuchten 146.457 geimpfte und zwischen Februar 2022 und Januar 2023 positiv auf SARS-CoV-2- getestete Personen im Alter von 60 bis 99 Jahren aus Bayern. Berechnet wurden adjustierte Hazard Ratios (aHR) für einen schweren Verlauf (COVID-19-bedingte Hospitalisierung oder Tod) in Abhängigkeit vom zeitlichen Abstand zwischen dem Eintritt einer vollständigen oder geboosterten Immunität und dem Infektionsdatum. Ergebnisse: Es wurden 3.342 (2,3%) schwere COVID-19-Verläufe innerhalb der ersten 60 Tage nach der Infektion beobachtet. Das Risiko eines schweren Verlaufs stieg mit zunehmendem Abstand zwischen dem Eintritt des Immunschutzes und der Infektion schrittweise an (aHR [95-%-Konfidenzintervall] nach 6, 9, 12 beziehungsweise 15 Monaten: 1,14 [1,08; 1,20]; 1,33 [1,24; 1,42]; 1,39 [1,25; 1,54]; 1,61 [1,35; 1,93]). Das Risiko stieg langsamer an, wenn ausschließlich mRNA-basierte Impfstoffe zur Anwendung gekommen waren. Wir haben in einer Vorgängerstudie eine anfängliche Wirksamkeit von 82% bei geboosterten (verglichen mit ungeimpften) Fälle ≥ 60 Jahre und eine absolute Risikoreduktion von 2,1% beobachtet. Überträgt man diese Ergebnisse auf unsere aktuelle Studie, so beträgt die verbleibende Wirksamkeit beziehungsweise die absolute Risikoreduktion nach sechs Monaten etwa 71% beziehungsweise 1,8% und nach 15 Monaten 32% beziehungsweise 0,8%. Schlussfolgerung: Diese Ergebnisse deuten darauf hin, dass während der Omikron-Welle der Schutz vor einem schweren COVID-19-Verlauf bei älteren Personen ab dem sechsten Monat nach Impfung graduell nachließ. Limitierungen sind nicht berücksichtigte Störfaktoren, eine mögliche Fehlklassifikation der Todesursache sowie ein Selektionsbias aufgrund fehlender Informationen über Impfstatus und schwere COVID-19-Verläufe.

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges.

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys® Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies). The anti-Spike seroprevalence was 94.7%, whereas, for anti-Nucleocapsid, it was only 6.9%. HCW status and contact with SARS-CoV-2-positive individuals were identified as infection risk factors, while vaccination and current smoking were associated with reduced risk. Older age correlated with higher anti-Nucleocapsid antibody levels, while vaccination and current smoking decreased the response. Vaccination alone or combined with infection led to higher anti-Spike antibody levels. Increasing time since the second vaccination, advancing age, and current smoking reduced the anti-Spike response. The cumulative number of cases in Munich affected the anti-Spike response over time but had no impact on anti-Nucleocapsid antibody development/seropositivity. Due to the significantly higher infection risk faced by HCWs and the limited number of significant risk factors, it is suggested that all HCWs require protection regardless of individual traits.

As early as March 2020, the authors of this letter started to work on surveillance data to obtain a clearer picture of the pandemic’s dynamic. This letter outlines the lessons learned during this peculiar time, emphasizing the benefits that better data collection, management, and communication processes would bring to the table. We further want to promote nuanced data analyses as a vital element of general political discussion as opposed to drawing conclusions from raw data, which are often flawed in epidemiological surveillance data, and therefore underline the overall need for statistics to play a more central role in public discourse.

Despite huge advances in local and systemic therapies, the 5-year relative survival rate for patients with metastatic CRC is still low. To avoid over- or undertreatment, proper risk stratification with regard to treatment strategy is highly needed. As EMT (epithelial-mesenchymal transition) is a major step in metastatic spread, this study analysed the prognostic effect of EMT-related genes in stage IV colorectal cancer patients using the study cohort of the FIRE-3 trial, an open-label multi-centre randomised controlled phase III trial of stage IV colorectal cancer patients. Overall, the prognostic relevance of EMT-related genes seems stage-dependent. EMT-related genes have no prognostic relevance in stage IV CRC as opposed to stage II/III.

A clustering outcome for high-dimensional data is typically interpreted via post-processing, involving dimension reduction and subsequent visualization. This destroys the meaning of the data and obfuscates interpretations. We propose algorithm-agnostic interpretation methods to explain clustering outcomes in reduced dimensions while preserving the integrity of the data. The permutation feature importance for clustering represents a general framework based on shuffling feature values and measuring changes in cluster assignments through custom score functions. The individual conditional expectation for clustering indicates observation-wise changes in the cluster assignment due to changes in the data. The partial dependence for clustering evaluates average changes in cluster assignments for the entire feature space. All methods can be used with any clustering algorithm able to reassign instances through soft or hard labels. In contrast to common post-processing methods such as principal component analysis, the introduced methods maintain the original structure of the features.

Over the course of the COVID-19 pandemic, Generalized Additive Models (GAMs) have been successfully employed on numerous occasions to obtain vital data-driven insights. In this article we further substantiate the success story of GAMs, demonstrating their flexibility by focusing on three relevant pandemic-related issues. First, we examine the interdepency among infections in different age groups, concentrating on school children. In this context, we derive the setting under which parameter estimates are independent of the (unknown) case-detection ratio, which plays an important role in COVID-19 surveillance data. Second, we model the incidence of hospitalizations, for which data is only available with a temporal delay. We illustrate how correcting for this reporting delay through a nowcasting procedure can be naturally incorporated into the GAM framework as an offset term. Third, we propose a multinomial model for the weekly occupancy of intensive care units (ICU), where we distinguish between the number of COVID-19 patients, other patients and vacant beds. With these three examples, we aim to showcase the practical and ‘off-the-shelf’ applicability of GAMs to gain new insights from real-world data.

High- and low pressure systems of the large-scale atmospheric circulation in the mid-latitudes drive European weather and climate. Potential future changes in the occurrence of circulation types are highly relevant for society. Classifying the highly dynamic atmospheric circulation into discrete classes of circulation types helps to categorize the linkages between atmospheric forcing and surface conditions (e.g. extreme events). Previous studies have revealed a high internal variability of projected changes of circulation types. Dealing with this high internal variability requires the employment of a single-model initial-condition large ensemble (SMILE) and an automated classification method, which can be applied to large climate data sets. One of the most established classifications in Europe are the 29 subjective circulation types called Grosswetterlagen by Hess & Brezowsky (HB circulation types). We developed, in the first analysis of its kind, an automated version of this subjective classification using deep learning. Our classifier reaches an overall accuracy of 41.1% on the test sets of nested cross-validation. It outperforms the state-of-the-art automatization of the HB circulation types in 20 of the 29 classes. We apply the deep learning classifier to the SMHI-LENS, a SMILE of the Coupled Model Intercomparison Project phase 6, composed of 50 members of the EC-Earth3 model under the SSP37.0 scenario. For the analysis of future frequency changes of the 29 circulation types, we use the signal-to-noise ratio to discriminate the climate change signal from the noise of internal variability. Using a 5%-significance level, we find significant frequency changes in 69% of the circulation types when comparing the future (2071–2100) to a reference period (1991–2020).

This dissertation develops new approaches for robustly estimating functional data structures and analyzing age-period-cohort (APC) effects, with applications in seismology and tourism science. The first part introduces a method that separates amplitude and phase variation in functional data, adapting a likelihood-based registration approach for generalized and incomplete data, demonstrated on seismic data. The second part presents generalized functional additive models (GFAMs) for analyzing associations between functional data and scalar covariates, along with practical guidelines and an R package. The final part addresses APC analysis, proposing new visualization techniques and a semiparametric estimation approach to disentangle temporal dimensions, with applications to tourism data, and is supported by the APCtools R package. (Shortened.)

Age-Period-Cohort (APC) analysis aims to determine relevant drivers for long-term developments and is used in many fields of science (Yang & Land, 2013). The R package APCtools offers modern visualization techniques and general routines to facilitate the interpretability of the interdependent temporal structures and to simplify the workflow of an APC analysis. Separation of the temporal effects is performed utilizing a semiparametric regression approach. We shortly discuss the challenges of APC analysis, give an overview of existing statistical software packages and outline the main functionalities of the package.

Background: Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use.
Methods: Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8–1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet).
Results: Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27–0.66], standard intake 0.99 g/kg [IQR 0.89– 1.09], and high intake 1.41 g/kg [IQR 1.29–1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome.
Conclusions: Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase.

Europe was hit by several, disastrous heat and drought events in recent summers. Besides thermodynamic influences, such hot and dry extremes are driven by certain atmospheric situations including anticyclonic conditions. Effects of climate change on atmospheric circulations are complex and many open research questions remain in this context, e.g., on future trends of anticyclonic conditions. Based on the combination of a catalog of labeled circulation patterns and spatial atmospheric variables, we propose a smoothed convolutional neural network classifier for six types of anticyclonic circulations that are associated with drought and heat. Our work can help to identify important drivers of hot and dry extremes in climate simulations, which allows to unveil the impact of climate change on these drivers. We address various challenges inherent to circulation pattern classification that are also present in other climate patterns, e.g., subjective labels and unambiguous transition periods.

Accounting for phase variability is a critical challenge in functional data analysis. To separate it from amplitude variation, functional data are registered, i.e., their observed domains are deformed elastically so that the resulting functions are aligned with template functions. At present, most available registration approaches are limited to datasets of complete and densely measured curves with Gaussian noise. However, many real-world functional data sets are not Gaussian and contain incomplete curves, in which the underlying process is not recorded over its entire domain. In this work, we extend and refine a framework for joint likelihood-based registration and latent Gaussian process-based generalized functional principal component analysis that is able to handle incomplete curves. Our approach is accompanied by sophisticated open-source software, allowing for its application in diverse non-Gaussian data settings and a public code repository to reproduce all results. We register data from a seismological application comprising spatially indexed, incomplete ground velocity time series with a highly volatile Gamma structure. We describe, implement and evaluate the approach for such incomplete non-Gaussian functional data and compare it to existing routines.

Aim: The treatment of tibial fractures with an intramedullary nail is an established procedure. However, torsional control remains challenging using intraoperatively diagnostic tools. Radiographic tools such as the Cortical Step Sign (CSS) and the Diameter Difference Sign (DDS) may serve as tools for diagnosing a relevant malrotation. The aim of this study was to investigate the effect of torsional malalignment on CSS and DDS parameters and to construct a prognostic model to detect malalignment.
Methods: A proximal tibial shaft fracture was set in human tibiae. Torsion was set stepwise from 0° to 30° in external and internal torsion. Images were obtained with a C-arm and transferred to a PC for measuring the medical cortical thickness (MCT), lateral cortical thickness (LCT), tibial diameter (TD) in AP and the anterior cortical thickness (ACT) as well as the posterior cortical thickness (PCT) and the transverse diameter (TD) of the proximal and the distal main fragment.
Results: There were significant differences between the various degrees of torsion for each of the absolute values of the examined variables. The parameters with the highest correlation were TD, LCT and ACT. A model combining ACT, LCT, PCT and TD lateral was most suitable model in identifying torsional malalignment. The best prediction of clinically relevant torsional malalignment, namely 15°, was obtained with the TD and the ACT.
Conclusion: This study shows that the CSS and DDS are useful tools for the intraoperative detection of torsional malalignment in proximal tibial shaft fractures and should be used to prevent maltorsion.

This study investigates how age, period, and birth cohorts are related to altering travel distances. We analyze a repeated cross-sectional survey of German pleasure travels for the period 1971–2018 using a holistic age–period–cohort (APC) analysis framework. Changes in travel distances are attributed to the life cycle (age effect), macro-level developments (period effect), and generational membership (cohort effect). We introduce ridgeline matrices and partial APC plots as innovative visualization techniques facilitating the intuitive interpretation of complex temporal structures. Generalized additive models are used to circumvent the identification problem by fitting a bivariate tensor product spline between age and period. The results indicate that participation in short-haul trips is mainly associated with age, while participation in long-distance travel predominantly changed over the period. Generational membership shows less association with destination choice concerning travel distance. The presented APC approach is promising to address further questions of interest in tourism research.

Registration for incomplete exponential family functional data.