Das Ausbreitungsverhalten von Plattenepithelkarzinomen der Haut

Diese Studie analysiert das Ausbreitungsverhalten der Plattenepithelkarzinome der Haut. Dabei wurde eine Fallzahl von 320 Patienten retrospektiv ausgewertet. (260 gewöhnliche-, 60 desmoplastische Plattenepithelkarzinome). Es handelt sich um den zweithäufigsten Tumor der Haut, der de novo oder aus Präkanzerosen hervorgeht und für den die UV Strahlung einen Risikofaktor darstellt. Es gibt mehrere Typen, hier relevant das gewöhnliche und das desmoplastische Plattenepithelkarzinome. Die Klinik ist variabel und kann mit einer pigmentierten, hyperkeratotischen Plaque mit entzündlichem Randsaum imponieren. Die Stadieneinteilung erfolgt nach TNM, die Malignitätseinteilung durch das Grading, die Risikoeinteilung nach der Tumordicke. „First line“ Therapie ist die operative Entfernung, weitere Möglichkeiten sind Strahlen- und Chemotherapie. Die Nachsorge erfolgt risikoadaptiert alle 3-6- oder 12 Monate. Die Plattenepithelkarzinome sind Tumoren der älteren Patienten und treten gehäuft zwischen 70-79 (35,6 %), 80-89 Jahren (38,4 %) und mit ca. 2/3 häufiger bei Männern, insbesondere an sonnenlichtexponierten Arealen, wie am Kopf (22,26 %), auf. Die Größe variiert und kann bis zu einem Durchmesser von 110 mm bei den gewöhnlichen Tumoren reichen, die zu 96,5 % einen Durchmesser von bis zu 50 mm erreichen. Die desmoplastischen Plattenepithelkarzinome erreichen aufgrund der Ausläuferbildung schnell einen größeren Durchmesser und werden in 95 % bis zu 73 mm, im Maximum der Ausreißer bis zu 120 mm groß. Die meisten Tumore sind mit 70,4 % G1 und mit 56,3 % low risk Tumore. Die high risk Gruppe bildet 35,8 % der desmoplastischen und 20,7 % der gewöhnlichen Plattenepithelkarzinome. Die Rate an R0 Resektionen nach der Primärexzision ist hoch, primäre R1 Resektionen kommen bei den desmoplastischen Plattenepithelkarzinome häufiger vor (10 % vs. 2,7 %). Um die Rate der Nachoperationen zu reduzieren wurden die desmoplastischen Typen mit primär größeren Sicherheitsabständen bis 10 mm exzidiert. Dadurch ist die oben genannte Rate der R1 Operationen zwischen gewöhnlichem und desmoplastischen Typ nicht signifikant unterschiedlich, folglich ein Exzisionsbias. Meistens wurde ein Sicherheitsabstand der Primärexzision der gewöhnlichen Tumore von 3-6 mm, bei den desmoplastischen häufig von >6 mm (28,1 %) verwendet. Diese wurden bis zu 6 Mal nachreseziert, die gewöhnlichen Plattenepithelkazinome maximal 2 Mal. Die Summe des insgesamt nötigen Sicherheitsabstands bis zur R0 Resektion beträgt bei den desmoplastischen- mehr, als bei den gewöhnlichen Plattenepithelkarzinome: In 97,3 % konnten die gewöhnlichen Plattenepithelkarzinome mit einem Sicherheitsabstand von 10 mm R0 reseziert werden, die desmoplastischen Tumore in 90 % mit einem Sicherheitsabstand von 21 mm. Die Rezidivrate beträgt beim gewöhnlichen- 5 % und 26,7 % beim desmoplastischen Plattenepithelkarzinom. Die Geschlechter (m=5,7 % / w=3,5 % gewöhnlich vs. m=25,6 % / w=29,4 % desmoplastisch) und auch die Altersklassen insgesamt zeigen ähnliche Rezidivraten ( 90 9,1 %). Die Rezidivrate wird weder von Alter, Geschlecht noch von dem primären Sicherheitsabstand beeinflusst (2,6 % bei 2 mm vs. 3,5 % bei 10 mm) oder beim desmoplastischen Plattenepithelkarzinom (20 % bei 2 mm vs. 41,7 % bei 10 mm). Die Anzahl der Nachexzisionen korreliert positiv mit der Rezidivrate (10,8 % bei 1NE vs. 33,3 % bei 3NE), was auf eine höhere Malignität schließen lässt. Die desmoplastischen Typen müssen trotz größerem primären Sicherheitsabstand signifikant häufiger nachoperiert werden. Die Metastasenrate ist bei insgesamt sehr gering, da durch das Hautkrebs-Screening frühe Formen detektiert werden. Metastasen entstehen primär lymphogen, meist in den ersten 2 Jahren postoperativ, woran die Nachsorgeintervalle angepasst sind. Das gewöhnliche Plattenepithelkarzinom metastasiert früher, rezidiviert aber durchschnittlich später (14 Monate gewöhnlich vs. 11,6 Monate desmoplastisch). Das desmoplastische Plattenepithelkarzinom zählt zu den high risk Tumoren mit einer Tumordicke >6mm und zeigt durch diese Ausbreitung höhere Rezidiv- und Metastasenraten. (8,3 % vs. 2,3 %). Die meisten Plattenepithelkarzinome können operativ komplikationslos in sano entfernt werden. Die Identifizierung der high risk Tumore ist essenziell. Ein beträchtlicher Risikofaktor ist die Anzahl der Nachexzisionen, die eine höhere Rezidivrate mit sich bringt und nur indirekt durch den primären Sicherheitsabstand beeinflusst wird

What lies beneath: Hydra provides cnidarian perspectives into the evolution of FGFR docking proteins

Across the Bilateria, FGF/FGFR signaling is critical for normal development, and in both Drosophila and vertebrates, docking proteins are required to connect activated FGFRs with downstream pathways. While vertebrates use Frs2 to dock FGFR to the RAS/MAPK or PI3K pathways, the unrelated protein, downstream of FGFR (Dof/stumps/heartbroken), fulfills the corresponding function in Drosophila. To better understand the evolution of the signaling pathway downstream of FGFR, the available sequence databases were screened to identify Frs2, Dof, and other key pathway components in phyla that diverged early in animal evolution. While Frs2 homologues were detected only in members of the Bilateria, canonical Dof sequences (containing Dof, ankyrin, and SH2/SH3 domains) were present in cnidarians as well as bilaterians (but not in other animals or holozoans), correlating with the appearance of FGFR. Although these data suggested that Dof coupling might be ancestral, gene expression analysis in the cnidarian Hydra revealed that Dof is not upregulated in the zone of strong FGFRa and FGFRb expression at the bud base, where FGFR signaling controls detachment. In contrast, transcripts encoding other, known elements of FGFR signaling in Bilateria, namely the FGFR adaptors Grb2 and Crkl, which are acting downstream of Dof (and Frs2), as well as the guanyl nucleotide exchange factor Sos, and the tyrosine phosphatase Csw/Shp2, were strongly upregulated at the bud base. Our expression analysis, thus, identified transcriptional upregulation of known elements of FGFR signaling at the Hydra bud base indicating a highly conserved toolkit. Lack of transcriptional Dof upregulation raises the interesting question, whether Hydra FGFR signaling requires either of the docking proteins known from Bilateria

Plant Diversity Surpasses Plant Functional Groups and Plant Productivity as Driver of Soil Biota in the Long Term

One of the most significant consequences of contemporary global change is the rapid decline of biodiversity in many ecosystems. Knowledge of the consequences of biodiversity loss in terrestrial ecosystems is largely restricted to single ecosystem functions. Impacts of key plant functional groups on soil biota are considered to be more important than those of plant diversity; however, current knowledge mainly relies on short-term experiments.We studied changes in the impacts of plant diversity and presence of key functional groups on soil biota by investigating the performance of soil microorganisms and soil fauna two, four and six years after the establishment of model grasslands. The results indicate that temporal changes of plant community effects depend on the trophic affiliation of soil animals: plant diversity effects on decomposers only occurred after six years, changed little in herbivores, but occurred in predators after two years. The results suggest that plant diversity, in terms of species and functional group richness, is the most important plant community property affecting soil biota, exceeding the relevance of plant above- and belowground productivity and the presence of key plant functional groups, i.e. grasses and legumes, with the relevance of the latter decreasing in time.Plant diversity effects on biota are not only due to the presence of key plant functional groups or plant productivity highlighting the importance of diverse and high-quality plant derived resources, and supporting the validity of the singular hypothesis for soil biota. Our results demonstrate that in the long term plant diversity essentially drives the performance of soil biota questioning the paradigm that belowground communities are not affected by plant diversity and reinforcing the importance of biodiversity for ecosystem functioning

Validation of the Maltese Adaptive Auditory Speech Test (AAST)

The Adaptive Auditory Speech Test (AAST) was developed to record the Speech Recognition Threshold (SRT) in children in quiet or with background noise. AAST is an interlingually valid and reliable standardised tool with speech material developed in several languages. The Maltese version of the Adaptive Auditory Speech Test (AAST) was developed to examine the speech recognition skills of 208 children and 40 Maltese-speaking adults in quiet, noise and high frequency. The aims were to determine the norms in these three settings in adults and children aged 4 years and older. The Maltese version of AAST confirms an age dependent norm threshold with a significant improvement in threshold being observed as children grow older, similar to other AAST versions. This was evident across the three test settings. An approximate difference of 10 dB was also noted between 4-year-old and 10-year-old children in AAST in quiet. Thresholds of 10-year-olds and adults were similar in both the quiet and high frequency versions. Implications for post Universal Newborn Hearing Screening using these tools are addressed

Validation of the LittlEARS (R) Questionnaire in Hearing Maltese-Speaking Children

Objectives: To adapt the LittlEARS (R) Auditory Questionnaire into the Maltese language and evaluate the psychometric properties of the Maltese version of the questionnaire for hearing children. Methods: The English version of LittlEARS (R) Auditory Questionnaire was adapted into Maltese using a translation/back translation procedure. In this cross-sectional study, a total of 398 parents of normal hearing children aged between 5 days and 36 months completed the Maltese version of LittlEARS (R). Psychometric validation was performed through scale analysis, item analysis, and analysis of reliability and validity. A non-linear regression model was derived to obtain normative data for expected and minimum values of total scores from the questionnaire according to age. Results: Predictive accuracy (Guttman's lambda) was 0.921, the Cronbach's alpha coefficient value was 0.921, and the split-half reliability coefficient was 0.949. The Pearson correlation coefficient between scores and age was 0.903. The regression analysis showed that 82% of the variance in the total scores can be explained by age. Norm curves were comparable to the original German data. Conclusion: This study confirmed that the Maltese version of LittlEARS (R) is a valid and reliable tool to evaluate auditory development in children less than two years of age

Validation of the LittlEARS® Questionnaire in Hearing Maltese-Speaking Children

Objectives: To adapt the LittlEARS® Auditory Questionnaire into the Maltese language and evaluate the psychometric properties of the Maltese version of the questionnaire for hearing children. Methods: The English version of LittlEARS® Auditory Questionnaire was adapted into Maltese using a translation/back translation procedure. In this cross-sectional study, a total of 398 parents of normal hearing children aged between 5 days and 36 months completed the Maltese version of LittlEARS®. Psychometric validation was performed through scale analysis, item analysis, and analysis of reliability and validity. A non-linear regression model was derived to obtain normative data for expected and minimum values of total scores from the questionnaire according to age. Results: Predictive accuracy (Guttman’s lambda) was 0.921, the Cronbach’s alpha coefficient value was 0.921, and the split-half reliability coefficient was 0.949. The Pearson correlation coefficient between scores and age was 0.903. The regression analysis showed that 82% of the variance in the total scores can be explained by age. Norm curves were comparable to the original German data. Conclusion: This study confirmed that the Maltese version of LittlEARS® is a valid and reliable tool to evaluate auditory development in children less than two years of age

The European Concept of Operations for U-space and Urban Air Mobility

CORUS-XUAM is the extension of the European U-space Concept of Operations (ConOps) – delivered by CORUS – covering Urban Air Mobility including passenger-carrying operations. Several parts of the updated ConOps will subsequently be demonstrated in a sequence of flight trials across seven European countries addressing different urban air mobility use-cases

Small number enumeration processes of deaf or hard-of-hearing students: A study using eye tracking and artificial intelligence

Students who are deaf or hard-of-hearing (DHH) often show significant difficulties in learning mathematics. Previous studies have reported that students who are DHH lag several years behind in their mathematical development compared to hearing students. As possible reasons, limited learning opportunities due to a lesser incidental exposure to numerical ideas, delays in language and speech development, and further idiosyncratic difficulties of students who are DHH are discussed; however, early mathematical skills and their role in mathematical difficulties of students who are DHH are not explored sufficiently. In this study, we investigate whether students who are DHH differ from hearing students in their ability to enumerate small sets (1-9)-an ability that is associated with mathematical difficulties and their emergence. Based on a study with N = 63 who are DHH and N = 164 hearing students from third to fifth grade attempting 36 tasks, we used eye tracking, the recording of students' eye movements, to qualitatively investigate student enumeration processes. To reduce the effort of qualitative analysis of around 8,000 student enumeration processes (227 students x 36 tasks), we used Artificial Intelligence, in particular, a clustering algorithm, to identify student enumeration processes from the heatmaps of student gaze distributions. Based on the clustering, we found that gaze distributions of students who are DHH and students with normal hearing differed significantly on a group level, indicating differences in enumeration processes, with students who are DHH using advantageous processes (e.g., enumeration at a glance) more often than hearing students. The results indicate that students who are DHH do not lag behind in small number enumeration as compared to hearing students but, rather, appear to perform better than their hearing peers in small number enumeration processes, as well as when conceptual knowledge about the part-whole relationship is involved. Our study suggests that the mathematical difficulties of students who are DHH are not related to difficulties in the small number enumeration, which offers interesting perspectives for further research