Hyperplasia to neoplasia sequence of duodenal and pancreatic neuroendocrine diseases and pseudohyperplasia of the PP-cells in the pancreas.

Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia-neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic-neoplastic neuroendocrine diseases.

Dynamics of the nasal microbiota in infancy: A prospective cohort study.

BACKGROUND Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.

Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approaches.

Haematuria in two geldings caused by osteochondroma of the os pubis: Case reports and anatomic study of the os pubis in 41 cadaveric pelvises

Exostosis of the os pubis causing haematuria, and potentially cystorrhexis, in horses has not been described in the literature. In this study, 2 geldings that suffered from exercise-induced haematuria caused by an osteochondroma of the os pubis, and the assessment of 41 cadaveric pubic bones are reported on. The anatomy of the os pubis is highly variable. The prevalence of exostosis in the os pubis appears to be higher in male horses. Palpation and ultrasonography of the pelvis per rectum and cystoscopy are valuable diagnostic tools. Depending on the extent of changes in the bladder wall, surgical removal of the exostosis should be considered in order to prevent cystorrhexis. In horses that present with haematuria, closer assessment of the os pubis for the presence of an exostosis is warranted.

MASP-1 of the complement system promotes clotting via prothrombin activation.

Mannan-binding lectin-associated serine protease-1 (MASP-1), a protein of the complement lectin pathway, resembles thrombin in terms of structural features and substrate specificity, and it has been shown to activate coagulation factors. Here we studied the effects of MASP-1 on clot formation in whole blood (WB) and platelet-poor plasma (PPP) by thrombelastography and further elucidated the underlying mechanism. Cleavage of prothrombin by MASP-1 was investigated by SDS-PAGE and N-terminal sequencing of cleavage products. Addition of MASP-1 or thrombin to WB and PPP shortened the clotting time and clot formation time significantly compared to recalcified-only samples. The combination of MASP-1 and thrombin had additive effects. In a purified system, MASP-1 was able to induce clotting only in presence of prothrombin. Analysis of MASP-1-digested prothrombin confirmed that MASP-1 cleaves prothrombin at three cleavage sites. In conclusion, we have shown that MASP-1 is able to induce and promote clot formation measured in a global setting using the technique of thrombelastography. We further confirmed that MASP-1-induced clotting is dependent on prothrombin. Finally, we have demonstrated that MASP-1 cleaves prothrombin and identified its cleavage sites, suggesting that MASP-1 gives rise to an alternative active form of thrombin by cleaving at the cleavage site R393.

Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles.

Melanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.

Land system science and sustainable development of the earth system: A global land project perspective

Land systems are the result of human interactions with the natural environment. Understanding the drivers, state, trends and impacts of different land systems on social and natural processes helps to reveal how changes in the land system affect the functioning of the socio-ecological system as a whole and the tradeoff these changes may represent. The Global Land Project has led advances by synthesizing land systems research across different scales and providing concepts to further understand the feedbacks between social-and environmental systems, between urban and rural environments and between distant world regions. Land system science has moved from a focus on observation of change and understanding the drivers of these changes to a focus on using this understanding to design sustainable transformations through stakeholder engagement and through the concept of land governance. As land use can be seen as the largest geo-engineering project in which mankind has engaged, land system science can act as a platform for integration of insights from different disciplines and for translation of knowledge into action.

Characterization of the dose distribution in the halo region of a clinical proton pencil beam using emulsion film detectors

Proton therapy is a high precision technique in cancer radiation therapy which allows irradiating the tumor with minimal damage to the surrounding healthy tissues. Pencil beam scanning is the most advanced dose distribution technique and it is based on a variable energy beam of a few millimeters FWHM which is moved to cover the target volume. Due to spurious effects of the accelerator, of dose distribution system and to the unavoidable scattering inside the patient's body, the pencil beam is surrounded by a halo that produces a peripheral dose. To assess this issue, nuclear emulsion films interleaved with tissue equivalent material were used for the first time to characterize the beam in the halo region and to experimentally evaluate the corresponding dose. The high-precision tracking performance of the emulsion films allowed studying the angular distribution of the protons in the halo. Measurements with this technique were performed on the clinical beam of the Gantry1 at the Paul Scherrer Institute. Proton tracks were identified in the emulsion films and the track density was studied at several depths. The corresponding dose was assessed by Monte Carlo simulations and the dose profile was obtained as a function of the distance from the center of the beam spot.

Unpacking reputational power: Intended and unintended determinants of the assessment of actors' power

The idea behind the reputational measure for assessing power of political actors is that actors involved in a decision-making process have the best view of their fellows' power. There has been, however, no systematic examination of why actors consider other actors as powerful. Consequently, it is unclear whether reputational power measures what it ought to. The paper analyzes the determinants of power attribution and distinguishes intended from unintended determinants in a data-set of power assessment covering 10 political decision-making processes in Switzerland. Results are overall reassuring, but nevertheless point toward self-promotion or misperception biases, as informants systematically attribute more power to actors with whom they collaborate.

Age constraints on the tectonic evolution of the Itremo region in Central Madagascar

The Itremo region in Central Madagascar comprises a deformed metasedimentary sequence (Itremo Group) that has undergone greenschist to lower amphibolite facies metamorphism. During a first phase of deformation (D1) Itremo Group sediments were deformed into a fold-and-thrust belt and transported toward the E to NE on top of migmatitic gneisses rocks of Anatananarivo block. A second phase of deformation (D2) affected both the fold-and-thrust belt and structurally underlying units, and formed large-scale N-S trending folds with steeply dipping axial planes. A Late Neoproterozoic Th–U–Pb XRF monazite age (565±17 Ma) dates the emplacement of a granite that truncates first-phase structures in the Itremo Group, and indicates that the fold-and-thrust belt formed prior to ≈565 Ma. Th–U–Pb electron microprobe dating was applied to elongated monazites that lie within the first-phase foliation of Itremo Group metapelites. The detrital cores of zoned monazites reveal two distinct age populations at ∼2000 and 1700 Ma, the latter age giving a maximum depositional age for the Itremo Group. Statistical analysis of ages determined from the rims of zoned monazites and from unzoned monazites indicates three Late Proterozoic–Early Paleozoic monazite growth events at about 565–540, 500 and 430 Ma. The oldest age population is contemporaneous within error, with the intrusion of the dated granite. The two younger age populations are found both in the Th–U–Pb and Ar–Ar data; together with the perturbation of the Rb–Sr system we interpret both ages as due to alteration related to fluid circulation events, possibly connected to the emplacement of pegmatite fields in Central Madagascar. Syn-D1 tectonic growth of contact metamorphism minerals such as andalusite has been observed locally in metapelites along the margin of Middle Neoproterozoic (≈800 Ma) granites, suggesting that D1 in the Itremo Group is contemporaneous with the intrusion of granites at ≈800 Ma. The N-S trending D2 folds are associated with ≈E-W shortening during the final assembly of Gondwana in Late Neoproterozoic–Early Cambrian times.