Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies

Economic Voting under Coalition Governments: Evidence from Germany

This article analyzes the impact of economic voting in federal elections for the German parliament. It combines theories of coalition politics and cabinet decision making—like prime ministerial government, collective cabinet decision making and ministerial discretion—with theoretical approaches on voting behavior to test which cabinet actor voters reward for improved economic conditions. The empirical results, which are based on data from German national election studies from 1987–2009, show that the party of the chancellor (and, thus, the strongest coalition party) benefits most from a positive evaluation of economic policy outcomes. There is, however, no consistent empirical evidence that the coalition parties collectively benefit from perceived positive economic performance. Therefore the findings demonstrate that economic voting occurs in German parliamentary elections, but is targeted specifically toward the chancellor's party

Relaxing the constant economic vote restriction : economic evaluations and party support in Germany

The popularity function literature has traditionally focused on incumbent government support, even under coalition governments. Here, we shift the focus from the government to the parties. To what extent are German parties held accountable for economic conditions when they hold the Chancellorship, serve in coalition, or sit in opposition? Using Seemingly Unrelated Regression to relax the Constant Economic Vote Restriction, we simultaneously model separate monthly party support functions for the Christian Democrats (CDU/CSU), Social Democrats (SPD), Liberals (FDP), and Greens over the post-unification period. After controlling for temporal dynamics and political factors, we find that economic evaluations have the strongest effect on support for the SPD and CDU/CSU when they hold the Chancellorship, and both of these parties are strongly affected when in opposition. The FDP remains insulated from economic perceptions, despite the party’s emphasis on economic policy. Additionally, economic evaluations do not significantly change support for the Greens as an issue party

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia

Background Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. Methods Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. Results From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). Conclusions This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices

Weder ein „modern gender gap“ noch „same gender voting“ in Deutschland? Zum Einfluss des Geschlechts auf das individuelle Wahlverhalten bei den Bundestagswahlen zwischen 1998 und 2013

Der Beitrag geht der Frage nach, ob ein Einfluss des Geschlechts auf die Wahlabsicht bei Wahlen zum Deutschen Bundestag zwischen 1998 und 2013 vorliegt. Auf der Grundlage der Literatur zum „modern gender gap“ einerseits sowie zum „same gender voting“ anderseits werden Hypothesen dahingehend abgeleitet, dass Frauen einen geringeren Anreiz haben sollten, christdemokratische Parteien zu wählen, und dass – als gegenläufige Erwartung – mit der Kanzlerkandidatur Angela Merkels seit 2005 Frauen verstärkt CDU oder CSU wählen sollten. Es zeigt sich weder ein durchgängiger Effekt für ein interessegeleitetes Wählen von Frauen, das sich in einer signifikant niedrigeren Wahrscheinlichkeit der Wahl der Unionsparteien hätte äußern sollen, noch Evidenz dafür, dass Frauen ab 2005 aufgrund der Kanzlerkandidatur Angela Merkels verstärkt CDU und CSU unterstützt haben. Lediglich 2013 zeigt sich in Westdeutschland eine Tendenz für den letztgenannten Zusammenhang. Demnach spielt das Geschlecht eines Wählers für die Wahlabsicht bei Bundestagswahlen kaum eine ausschlaggebende Rolle

The "Woundosome" Concept and Its Impact on Procedural Outcomes in Patients With Chronic Limb-Threatening Ischemia

This editorial assembles endovascular specialists from diverse clinical backgrounds and nationalities with a global call to address key challenges to enhance revascularization in chronic limb-threatening ischemia (CLTI) patients.- Dedicated below-the-ankle (BTA) angiography and revascularization is underutilized in ischemic foot treatment. Existing guidelines do not address comprehensive BTA vessel analysis. CLTI trials also often lack data on in-line arterial flow to the ischemic lesion and BTA vessel evaluation, hindering outcome assessment.- Dedicated multi-planar angiographic evaluation of the distal microcirculation is key: Direct arterial flow or good-quality collaterals are crucial in influencing wound healing and need to be assessed diligently to the level of the distal ischemic wound territory, termed “woundosome.”- An important primary emphasis of future trials should be on validating technologies and strategies for assessing tissue perfusion before, during, and after revascularization undertaken to heal tissue loss in CLTI patients. This will allow determination of a potentially significant delta in tissue perfusion prior to and following intervention at the “woundosome” level. Once changes in arterial perfusion have been identified as positively correlated to wound healing, these could serve as a much-needed novel primary technical outcome measure for patients with tissue loss undergoing surgical, hybrid, or endovascular revascularization