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Radiosonde measurements obtained at the Arctic site Ny-Ålesund (78.9°N, 11.9°E), Svalbard, from 1993 to 2014 have been homogenized accounting for instrumentation discontinuities by correcting known errors in the manufacturer provided profiles. The resulting homogenized radiosonde record is provided as supplementary material at http://doi.pangaea.de/10.1594/PANGAEA.845373 . From the homogenized data record, the first Ny-Ålesund upper-air climatology of wind, temperature and humidity is presented, forming the background for the analysis of changes during the 22-year period. Particularly during the winter season, a strong increase in atmospheric temperature and humidity is observed, with a significant warming of the free troposphere in January and February up to 3 K per decade. This winter warming is even more pronounced in the boundary layer below 1 km, presumably amplified by mesoscale processes including e.g. orographic effects or the boundary layer capping inversion. Though the largest contribution to the increasing atmospheric water vapour column in winter originates from the lowermost 2 km, no increase in the contribution by specific humidity inversions is detected. Instead, we find an increase in the humidity content of the large-scale background humidity profiles. At the same time, the tropospheric flow in winter is found to occur less frequent from northerly directions and to the same amount more frequent from the South. We conclude that changes in the atmospheric circulation lead to an enhanced advection of warm and moist air from lower latitudes to the Svalbard region in the winter season, causing the warming and moistening of the atmospheric column above Ny-Ålesund, and link the observations to changes in the Arctic Oscillation.

One of the most widely used systems for wind speed and direction observations at meteorological sites is based on Doppler wind lidar (DWL) technology. The wind vector derivation strategies of these instruments rely on the assumption of stationary and homogeneous horizontal wind, which is often not the case over heterogeneous terrain. This study focuses on the validation of two DWL systems, operated by the German Weather Service [Deutscher Wetterdienst (DWD)] and installed at the boundary layer field site Falkenberg (Lindenberg, Germany), with respect to measurements from a small, fixed-wing uncrewed aircraft system (UAS) of the type Multi-Purpose Airborne Sensor Carrier (MASC-3). A wind vector intercomparison at an altitude range from 100 to 500 m between DWL and UAS is performed, after a quality control of the aircraft’s data accuracy against a cup anemometer and wind vane mounted on a meteorological mast also operating at the location. Both DWL systems exhibit an overall root-mean-square difference in the wind vector retrieval of less than 22% for wind speed and lower than 18° for wind direction. The enhancement or deterioration of these statistics is analyzed with respect to scanning height and atmospheric stability. The limitations of this type of validation approach are highlighted and accounted for in the analysis.

The global demand for products that effectively prevent the development of male-pattern baldness (MPB) has drastically increased. However, there is currently no established genetic model for the estimation of MPB risk. We conducted a prediction analysis using single-nucleotide polymorphisms (SNPs) identified from previous GWASs of MPB in a total of 2725 German and Dutch males. A logistic regression model considering the genotypes of 25 SNPs from 12 genomic loci demonstrates that early-onset MPB risk is predictable at an accuracy level of 0.74 when 14 SNPs were included in the model, and measured using the area under the receiver-operating characteristic curves (AUC). Considering age as an additional predictor, the model can predict normal MPB status in middle-aged and elderly individuals at a slightly lower accuracy (AUC 0.69-0.71) when 6-11 SNPs were used. A variance partitioning analysis suggests that 55.8% of early-onset MPB genetic liability can be explained by common autosomal SNPs and 23.3% by X-chromosome SNPs. For normal MPB status in elderly individuals, the proportion of explainable variance is lower (42.4% for autosomal and 9.8% for X-chromosome SNPs). The gap between GWAS findings and the variance partitioning results could be explained by a large body of common DNA variants with small effects that will likely be identified in GWAS of increased sample sizes. Although the accuracy obtained here has not reached a clinically desired level, our model was highly informative for up to 19% of Europeans, thus may assist decision making on early MPB intervention actions and in forensic investigations.

Landmarking of 3D facial surface scans is an important analysis step in medical and biological applications, such as genome-wide association studies (GWAS). Manual landmarking is often employed with considerable cost and rater dependent variability. Landmarking automatically with minimal training is therefore desirable. We apply statistical ensemble methods to improve automated landmarking of 3D facial surface scans. Base landmarking algorithms using features derived from 3D surface scans are combined using either bagging or stacking. A focus is on low training complexity of maximal 40 training samples with template based landmarking algorithms that have proved successful in such applications. Additionally, we use correlations between landmark coordinates by introducing a search strategy guided by principal components (PCs) of training landmarks. We found that bagging has no useful impact, while stacking strongly improves accuracy to an average error of 1.7 mm across all 21 landmarks in this study, a 22% improvement as compared to a previous, comparable algorithm. Heritability estimates in twin pairs also show improvements when using facial distances from landmarks. Ensemble methods allow improvement of automatic, accurate landmarking of 3D facial images with minimal training which is advantageous in large cohort studies for GWAS and when landmarking needs change or data quality varies.

Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany ( N =529) and the Netherlands ( N =2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort ( P =6 × 10 −4 ), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene ( P =0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

Climate change impacts will affect grassland farming in various ways in the future. Communication and knowledge transfer are crucial to implement on-farm adaptation measures required to meet these challenges in a timely way. Therefore, we need to know how grassland farmers perceive climate change and which factors influence their attitude. We hypothesized that besides direct factors such as region, farm size, age and education, farmers’ socio-cultural background and their beliefs and attitudes are most important in their reaction to climate change. To investigate this, we conducted a survey with extensive on-farm interviews ( n  = 82) in four distinctive regions in the North German Plain on a gradient from sub-maritime to areas with sub-continental climate. We found that with a more continental climate and less rainfall and with increasing farm size, grassland farmers were more aware of the implications of climate change. In a second step, to categorize the influence of personal beliefs on decisions concerning farming, we applied the typology approach and distinguished four farming styles. Farmers in the four groups differed in terms of climate change awareness and adaptation preferences ( P  < 0.05). Yield Optimizers and Modernists were more open-minded to rational and economic facts and showed a significantly greater willingness to implement adaptation measures than Idealists and Traditionalists, who need to be addressed at a more emotional level. The results of this study may contribute to the development of better‐targeted adaptation policies that will serve specific groups of farmers more effectively.

Primary neuroendocrine carcinoma of the breast (NECB) as defined by the World Health Organization (WHO) in 2012 is a rare, but possibly under-diagnosed entity. It is heterogeneous as it entails a wide spectrum of diseases comprising both well-differentiated neuroendocrine tumors of the breast as well as highly aggressive small cell carcinomas. Retrospective screening of hospital charts of 612 patients (2008–2019) from our specialized outpatient unit for neuroendocrine neoplasia revealed five patients diagnosed with NECB. Given the low prevalence of these malignancies, correct diagnosis remains a challenge that requires an interdisciplinary approach. Specifically, NECB may be misclassified as carcinoma of the breast with neuroendocrine differentiation, carcinomas of the breast of no special type/invasive ductal carcinoma, or a metastasis to the breast. Therefore, this study presents multifaceted characteristics as well as the clinical course of these patients and discusses the five cases from our institution in the context of available literature.

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10−8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10−3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

Background About 50% of older patients with acute myeloid leukemia (AML) fail to attain complete remission (CR) following cytarabine plus anthracycline-based induction therapy. Salvage chemotherapy regimens are based on high-dose cytarabine (HiDAC), which is frequently combined with mitoxantrone (HAM regimen). However, CR rates remain low, with less than one-third of the patients achieving a CR. FLT3 -ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory (r/r)-AML. One-quarter of patients who received midostaurin are refractory to induction therapy and relapse rate at 2 years exceeds 40%. The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is a very selective FLT3 inhibitor, has a high capacity for sustained FLT3 inhibition, and has an acceptable toxicity profile. Methods In this multicenter, upfront randomized phase II trial, all patients receive quizartinib combined with HAM (cytarabine 3g/m 2 bidaily day one to day three, mitoxantrone 10mg/m 2 days two and three) during salvage therapy. Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach with achievement of CR, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial recovery of peripheral blood counts (CRh) as primary endpoint. During consolidation therapy (chemotherapy and allogeneic hematopoietic cell transplantation), patients receive either prophylactic quizartinib therapy or measurable residual disease (MRD)-triggered preemptive continuation therapy with quizartinib according to up-front randomization. The matched threshold crossing approach is a novel study-design to enhance the classic single-arm trial design by including matched historical controls from previous clinical studies. It overcomes common disadvantages of single-armed and small randomized studies, since the expected outcome of the observed study population can be adjusted based on the matched controls with a comparable distribution of known prognostic and predictive factors. Furthermore, balanced treatment groups lead to stable statistical models. However, one of the limitations of our study is the inability to adjust for unobserved or unknown confounders. Addressing the primary endpoint, CR/CRi/CRh after salvage therapy, the maximal sample size of 80 patients is assessed generating a desirable power of the used adaptive design, assuming a logistic regression is performed at a one-sided significance level α =0.05, the aspired power is 0.8, and the number of matching partners per intervention patient is at least 1. After enrolling 20 patients, the trial sample size will be recalculated in an interim analysis based on a conditional power argument. Conclusion Currently, there is no commonly accepted standard for salvage chemotherapy treatment. The objective of the salvage therapy is to reduce leukemic burden, achieve the best possible remission, and perform a hemopoietic stem-cell transplantation. Thus, in patients with FLT3 -ITD mutation, the comparison of quizartinib with intensive salvage therapy versus chemotherapy alone appears as a logical consequence in terms of efficacy and safety. Ethics and dissemination Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. Trial registration ClinicalTrials.gov NCT03989713; EudraCT Number: 2018-002675-17.

Intraoperative hypotension (IOH) presents a risk factor for postoperative organ dysfunction. However, as a unique definition of IOH is still missing, the influence of individual preoperative patient characteristics on IOH remains poorly understood. This systematic review aimed to examine the variability in IOH definitions and to identify preoperative risk factors associated with IOH. A systematic literature search was conducted from inception to March 2, 2024. Studies reporting on IOH and from which the association between preoperative characteristics and IOH in cardiac and non-cardiac surgery could be derived were included. Odds ratios (ORs) were either extracted directly or calculated based on available patient-level data. Pooled estimates were generated using a random-effects model. Out of 7,361 screened studies, 78 met the inclusion criteria. Heterogeneity was high due to varying IOH definitions. 14 preoperative factors were included in the meta-analysis. Older age (OR 1.03, 95% CI 1.02-1.04) and female sex (OR 1.16, 95% CI 1.08-1.24) were associated with increased IOH risk. ASA-II was linked to lower risk compared to ASA-III (OR 0.80, 95% CI 0.70-0.91). Diabetes mellitus (OR 1.18, 95% CI 1.04-1.35) and arterial hypertension (OR 1.56, 95% CI 1.33-1.83) were independent predictors. ACE inhibitor use (angiotensin-converting enzyme inhibitor use; OR 1.63, 95% CI 1.42-1.88), angiotensin receptor blocker (ARB) use (OR 1.38, 95% CI 1.01-1.89), and emergent surgery (OR 1.25, 95% CI 1.09-1.42) also increased IOH incidence. The risk of bias was low to moderate. The substantial variability in IOH definitions and several preoperative IOH influencing patient characteristics highlight the need for standardized criteria to improve comparability and guide personalized perioperative management. identifier PROSPERO CRD42024514229.