First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension.

UNLABELLED This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were -11.6±25.3 and -6.6±18.0 mm Hg for all patients (P<0.001 for both) and -20.3±22.8 and -8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT01534299.

To research living beings one has to participate in life.' Viktor von Weizsäcker's legacy

Viktor von Weizsäcker has been a German medical doctor and philosopher, well known throughout Europe, but hardly received in the Anglo-American culture. He focusses on the crucial epistemological question how one can conduct research on living beings. The article’s title represents a key quote of his opus magnum “Der Gestaltkreis”, which works out a theory of the unity of perception and motion. According to Viktor von Weizsäcker, one cannot separate the two, meaning that we locate ourselves in a fundamental union with the living world, which has lasting influence on our capacity of perception. This idea does not seem too different from Ian Barbour’s idea about critical realism, exploring a “consciousness of ourselves as arising out of rapport, interconnection and participation in processes reaching beyond ourselves.” Both authors, Viktor von Weizsäcker and Ian Barbour, still have lasting influence on the dialog between religion and science, each in their respective cultures – a further reason to compare their core ideas, after presenting Viktor von Weizsäcker’s life and thought. Finally, the theological impact of von Weizsäcker’s thought will be assessed. Following his philosophy, it becomes clear that the miracle of creation is the condition of the possibility of any perception.

"Leiomyomatoid angiomatous neuroendocrine tumor" (LANT) of the pituitary reflects idiosyncratic angiogenesis in adenomas of the gonadotroph cell lineage.

Based on a single-case observation, the descriptive label "leiomyomatoid angiomatous neuroendocrine tumor" (LANT) has been tentatively applied to what was perceived as a possible novel type of dual-lineage pituitary neoplasm with biphasic architecture. We report on two additional examples of an analogous phenomenon encountered in male patients, aged 59 years (Case 1) and 91 years (Case 2). Both tumors were intra- and suprasellar masses, measuring 5.6 cm × 4.4 cm × 3.4 cm, and 2.7 cm × 2 cm × 1.7 cm, respectively. Histologically, Case 1 was an FSH-cell adenoma interwoven by vascularized connective tissue septa that tended to exhibit incremental stages of adventitial overgrowth. The epithelial component of Case 2 corresponded to an LH-cell adenoma, and lay partitioned by a maze of paucicellular to hyalinized vascular axes. Irrespective of architectural variations, perivascular spindle cells exhibited immunopositivity for vimentin, muscular actin, and smooth muscle actin. Conversely, negative results were obtained for CD34, EMA, S100 protein, GFAP, and TTF-1. Ultrastructural study failed to reveal metaplastic cell forms involving transitional features between adenohypophyseal-epithelial and mesenchymal-contractile phenotype. We propose that LANT be regarded as a peculiar reflection of maladaptive angiogenesis in some pituitary adenomas, rather than a genuine hybrid neoplasm. While no mechanistic clue is forthcoming to account for this distinctive pattern, hemodynamic strain through direct arterial - rather than portal - supply of the adenoma's capillary bed may be one such explanatory factor. The apparent predilection of the LANT pattern for macroadenomas of the gonadotroph cell lineage remains unexplained.

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.

The first major incision of the Swiss Deckenschotter landscape

The Swiss Deckenschotter (“cover gravels”) is the oldest Quaternary units in the northern Swiss Alpine Foreland. They are a succession of glaciofluvial gravel layers intercalated with glacial and/or overbank deposits. This lithostratigraphic sequence is called Deckenschotter because it “covers” Molasse or Mesozoic bedrock and forms mesa-type hill-tops. Deckenschotter occurs both within and beyond the extent of the Last Glacial Maximum glaciers. The Swiss Deckenschotter consist of two sub-units: Höhere (Higher) and Tiefere (Lower) Deckenschotter. Although the Höhere Deckenschotter sub-unit (HDS) is topographically higher than the Tiefere Deckenschotter, it is older. The only available age for the Swiss Deckenschotter is 2.5–1.8 Ma based on mammal remains found in HDS at the Irchel site. In this study, we present an exposure age for the topographically lowest HDS, calculated from a cosmogenic 10Be depth-profile. Our results show that the first phase of the Deckenschotter glaciations in the Swiss Alps terminated at least 1,020+80−120 ka ago, which is indicated by a significant fluvial incision. This line of evidence seems to be close to synchronous with the beginning of the Mid-Pleistocene Revolution, when the frequency of the glacial-interglacial cyclicity changed from 41 to 100 ka and the amplitude from low to high, between marine isotope stages 23 and 22.

Formungen neuzeitlicher Religionsverständnisse: Eine Landpredigt zum Thema "Was ist Religion?" (1799)

In den letzten drei Jahrzehnten ist das Interesse an einer historischen Verortung und Aufarbeitung der Entstehung neuzeitlicher Religionsverständnisse stetig gewachsen. Erst 2011 hat Michael Bergunder in der ZfR die Forderung nach einer konsequenten Historisierung von „Religion“ erneuert. Die Umsetzung eines solchen Programms orientiert sich bis heute stark an elitären, akademischen, intellektuellen Quellen, die in eine direkte Genealogie mit der im 19. Jahrhundert entstehenden Religionswissenschaft zu bringen sind. Mit der Forderung nach der Historisierung von Alltagsverständnissen von „Religion“ muss diese Perspektive jedoch erweitert werden, um auch nicht-elitäre Diskursstränge erfassen zu können. Zudem ist eine stärkere und konkretere historische Verortung der Diskursbeiträge anzustreben. Der Beitrag möchte zu einem solchen Programm einen Beitrag leisten, indem er die im April 1799 im Dorf Schwarzenbach bei Luzern gehaltene Predigt des katholischen Vikars Andreas Estermann zum Ausgangspunkt nimmt, die unter dem programmatischen Titel „Was ist Religion?“ stand. An ihr lässt sich zeigen, wie stark in diesem Fall die konkrete Ausformung des Religionsverständnisses von den Kontextfaktoren der Französischen Revolution, ihrer Umsetzung in der Helvetik, der lokalen Unruhen und Säkularisationen abhängig ist. Zudem kann gezeigt werden, wie Elemente eines oft im späten 19. Jahrhundert verorteten „protestantischen“ Religionsbegriffs bereits im späten 18. Jahrhundert in einem katholischen Kontext angelegt sind. Der Artikel stellt damit einige gängige Grundannahmen zur Geschichte moderner Religionsverständnisse in Frage.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.