Evaluating the effects of a risk-adapted screening program for familial colorectal cancer in individuals between 25 and 50 years of age: study protocol for the prospective population-based intervention study FARKOR

BACKGROUND Colorectal cancer (CRC) is the second most common malignant disease and the second most common cause of cancer death in Germany. Official CRC screening starts at age 50. As there is evidence that individuals with a family history of CRC have an increased risk of developing CRC before age 50, there are recommendations to start screening for this group earlier. This study aims to evaluate the clinical and economic effects of a risk-adapted screening program for CRC in individuals between 25 and 50 years of age with potentially increased familial CRC risk. METHODS FARKOR (Familiäres Risiko für das Kolorektale Karzinom) is a population-based prospective intervention study. All members of cooperating statutory health insurance companies between 25 and 50 years of age living in a model region in Germany (federal state of Bavaria, 3.5 million inhabitants in this age group) can participate in the program between October 2018 and March 2020. Recruitment takes place through physicians and through a public campaign. Additionally, insurances contact recently diagnosed CRC patients in order to encourage their relatives to participate in the program. Physicians assess a participant's familial history of CRC using a short questionnaire. All participants with a family history of CRC are invited to a shared decision making process to decide on further screening options consisting of either undergoing an immunological test for fecal occult blood or colonoscopy. Comprehensive data collection based on self-reported lifestyle information, medical documentation and health administrative databases accompanies the screening program. Longterm benefits, harms and the cost-effectiveness of the risk-adapted CRC screening program will be assessed by decision analytic modeling. DISCUSSION The data collected in this study will add important pieces of information that are still missing in the evaluation of the effects and the cost-effectiveness of a risk-adapted CRC screening strategy for individuals under 50 years of age. TRIAL REGISTRATION German Clinical Trials Register, DRKS-IDDRKS00015097

Comparison of different methods to obtain and store liver biopsies for molecular and histological research

BACKGROUND: To minimize the necessary number of biopsies for molecular and histological research we evaluated different sampling techniques, fixation methods, and storage procedures for canine liver tissue. For addressing the aim, three biopsy techniques (wedge biopsy, Menghini, True-cut), four storage methods for retrieval of RNA (snap freezing, RNAlater, Boonfix, RLT-buffer), two RNA isolation procedures (Trizol and RNAeasy), and three different fixation protocols for histological studies (10% buffered formalin, RNAlater, Boonfix) were compared. Histological evaluation was based on hematoxylin-eosin (HE) and reticulin (fibrogenesis) staining, and rubeanic acid and rhodanine stains for copper. Immunohistochemical evaluation was performed for cytokeratin-7 (K-7), multidrug resistance binding protein-2 (MRP-2) and Hepar-1. RESULTS: RNA quality was best guaranteed by the combination of a Menghini biopsy with NaCl, followed by RNAlater preservation and RNAeasy mini kit extraction. These results were confirmed by quantitative RT-PCR testing. Reliable histological assessment for copper proved only possible in formalin fixed liver tissue. Short formalin fixation (1-4 hrs) improved immunohistochemical reactivity and preservation of good morphology in small liver biopsies. CONCLUSION: At least two biopsies (RNAlater and formalin) are needed. Since human and canine liver diseases are highly comparable, it is conceivable that the protocols described here can be easily translated into the human biomedical field

Neutron activation analysis and X-ray Rayleigh and Raman scattering of hair and nail clippings as noninvasive bioindicators for Cu liver status in Labrador Retrievers

The heritability of chronic hepatitis in the Labrador Retriever is studied with the aim of identifying the related gene mutation. Identification of cases and controls is largely based on instrumental neutron activation analysis (INAA) Cu determination in liver biopsies. The burden for these companion animals may be reduced if nail clippings and hair (fur) could serve as a noninvasive indicator for the hepatic Cu concentrations. No correlation was found between hepatic Cu concentrations and Cu concentrations in hair and nail samples. However, hair and nail samples were also analyzed by X-ray tube excitation, taking advantage of the X-ray Compton, Rayleigh, and Raman scattering which reflects the organic components such as the type of melanin. Principal component analysis provided first indications that some differentiation between healthy and sick dogs could indeed be obtained from hair and nail analysis

Detection of Helicobacter pylori in bile of cats

Lymphocytic cholangitis (LC) in cats is a biliary disease of unknown etiology. Helicobacter spp. were recently implicated in human primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Because of the similarities between PSC/PBC with LC, we hypothesized that Helicobacter spp. are involved in feline LC. A PCR with Helicobacter genus-specific 16S rRNA primers was performed on DNA isolated from feline bile samples. Four of the 15 (26%) LC samples were positive, whereas only 8/51 (16%) of non-LC samples were PCR positive (p=0.44). Sequence analysis of the amplicons revealed a 100% identity with the Helicobacter pylori specific DNA fragments. Our data suggest an etiological role of H. pylori in feline LC and that cats are a potential zoonotic reservoir

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Spatial behavior in relation to mating systems: movement patterns, nearest-neighbor distances, and mating success in diploid and polyploid frog hybrids (Pelophylax esculentus)

Mating success depends not only on genetic and phenotypic characteristics of males and females but also on their spatial position relative to other individuals, which influences the chances for interactions. Hence, any behavior that affects proximity to other individuals can potentially translate into fitness gain or loss. Here, we investigate the effects of genotype on male movement and distance to nearest neighbor (DNN) in three populations of the edible frog Pelophylax esculentus, a natural hybrid between its parental species Pelophylax ridibundus(genotype RR) and Pelophylax lessonae (LL). The system is particularly suited for such an analysis because the fitness differences between mating with a certain genotype are particularly strong. Moreover, which genotype should be preferred differs among populations where diploid hybrids (LR) live in sympatry withP. lessonae (L–E system) and those where diploid hybrids occur in allhybrid populations together with triploids (LLR and/or LRR) (E–E system). Hence, we expected differences among genotypes in movement patterns and spatial arrangement within the breeding pond. We did, indeed, find such differences. They were predominantly due to density differences between populations, followed by size and condition differences between males. Most relevant for our question was a difference in DNN: in the E–E system, distances between all three hybrid types were equal, whereas in the L–E system LR hybrids tended to stay closer to LL than to other LR. The results are discussed in relation to previous mate choice experiments and theoretical models about mating preferences in the two systems

Spatial behavior in relation to mating systems: movement patterns, nearest-neighbor distances, and mating success in diploid and polyploid frog hybrids ( Pelophylax esculentus )

Mating success depends not only on genetic and phenotypic characteristics of males and females but also on their spatial position relative to other individuals, which influences the chances for interactions. Hence, any behavior that affects proximity to other individuals can potentially translate into fitness gain or loss. Here, we investigate the effects of genotype on male movement and distance to nearest neighbor (DNN) in three populations of the edible frog Pelophylax esculentus, a natural hybrid between its parental species Pelophylax ridibundus (genotype RR) and Pelophylax lessonae (LL). The system is particularly suited for such an analysis because the fitness differences between mating with a certain genotype are particularly strong. Moreover, which genotype should be preferred differs among populations where diploid hybrids (LR) live in sympatry with P. lessonae (L-E system) and those where diploid hybrids occur in all-hybrid populations together with triploids (LLR and/or LRR) (E-E system). Hence, we expected differences among genotypes in movement patterns and spatial arrangement within the breeding pond. We did, indeed, find such differences. They were predominantly due to density differences between populations, followed by size and condition differences between males. Most relevant for our question was a difference in DNN: in the E-E system, distances between all three hybrid types were equal, whereas in the L-E system LR hybrids tended to stay closer to LL than to other LR. The results are discussed in relation to previous mate choice experiments and theoretical models about mating preferences in the two systems

Geospatial Natural Language in Indigenous Australia: Research Priorities

International audienceAustralian languages are widely believed to exemplify abstract spatial conceptual systems, manifest as cardinal terms. In fact, Australian languages typically make heavy use of terms invoking local environmental features. We report on research investigating correlations between linguistic spatial systems and topography, and the role of socio-cultural factors in individual variation in spatial referential strategy choices

Frames of spatial reference in five Australian languages

International audienceAustralian Indigenous languages are widely cited as depending overwhelmingly on abstract cardinal terms for spatial reference. However, considerable under-recognized diversity exists, with systems invoking aspects of local topography or egocentric projections. The first step toward an empirically grounded understanding of the wider implications of Australian spatial reference systems is to establish what components of spatial systems actually occur in what combinations across the continent. This article examines the spatial systems of five Australian languages to test hypotheses about the role of the environment in shaping linguistic representations of space, revealing under-recognized aspects of Australian systems, including the use of egocentric ("relative") reference frame but only on the sagittal axis; a nearside-farside system; and multiple systems invoking diverse salient environmental features