CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD

Age-related macular degeneration (AMD) is a prevalent cause of blindness in Western societies. Variants in the genes encoding complement factor H (CFH), complement component 3 (C3) and age-related maculopathy susceptibility 2 (ARMS2) have repeatedly been shown to confer significant risks for AMD; however, their role in disease progression and thus their potential relevance for interventional therapeutic approaches remains unknown. Here, we analyzed association between variants in CFH, C3 and ARMS2 and disease progression of geographic atrophy (GA) due to AMD. A quantitative phenotype of disease progression was computed based on longitudinal observations by fundus autofluorescence imaging. In a subset of 99 cases with pure bilateral GA, variants in CFH (Y402H), C3 (R102G), and ARMS2 (A69S) are associated with disease (P = 1.6x10(-9), 3.2x10(-3), and P = 2.6x10(-12), respectively) when compared to 612 unrelated healthy control individuals. In cases, median progression rate of GA over a mean follow-up period of 3.0 years was 1.61 mm(2)/year with high concordance between fellow eyes. No association between the progression rate and any of the genetic risk variants at the three loci was observed (P>0.13). This study confirms that variants at CFH, C3, and ARMS2 confer significant risks for GA due to AMD. In contrast, our data indicate no association of these variants with disease progression which may have important implications for future treatment strategies. Other, as yet unknown susceptibilities may influence disease progression

SFB 880: aeroacoustic research for low noise take-off and landing

This paper gives an overview about prediction capabilities and the development of noise reduction technologies appropriate to reduce high lift noise and propeller noise radiation for future low noise transport aircraft with short take-off and landing capabilities. The work is embedded in the collaborative research centre SFB 880 in Braunschweig, Germany. Results are presented from all the acoustics related projects of SFB 880 which cover the aeroacoustic simulation of the effect of flow permeable materials, the characterization, development, manufacturing and operation of (porous) materials especially tailored to aeroacoustics, new propeller arrangements for minimum exterior noise due to acoustic shielding as well as the prediction of vibration excitation of aircraft structures, reduced by porous materials

The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction

Hidradenitis suppurativa (HS)(also designated acne inversa)is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1β turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1β–induced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1β response, which was not clearly shared or strengthened by other cytokines. The IL-1β signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1β pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1β and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1β pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels. © 2018 The Author

Aircraft and technology for low noise short take-off and landing

This paper discusses characteristic multi-disciplinary issues related to quiet short take-off and landing for civil transport aircraft with a typical short to medium range mission. The work reported here is focussing on the noise aspects and is embedded in the collaborative research centre CRC880 in Braunschweig, Germany. This long term aircraft Research initiative focusses on a new transport aircraft segment for operation on airports with shorter runway length in commercial air transport. This calls for a community-friendly aircraft designed for operations much closer to the home of its passengers than today. This Scenario sets challenging, seemingly contradictory aircraft technology requirements, namely those for extreme lift augmentation at low noise. The Research Centre CRC880 has therefore devised a range of technology projects that aim at significant noise reductions and at the generation of e�cffient and flexible high lift. The research also addresses flight Dynamics of aircraft at takeoff and landing. It is envisaged that in general significant noise reduction -compared to a reference turbofan driven aircraft of year 2000 technology- necessarily requires component noise reduction in combination with a low noise a/c concept. Results are presented from all the acoustics related projects of CRC880 which cover the aeroacoustic simulation of the source noise reduction by flow permeable materials, the characterization, development, manufacturing and operation of (porous) materials especially tailored to aeroacoustics, new UHBR turbofan arrangements for minimum exterior noise due to acoustic shielding as well as the prediction of jet noise vibration excitation of cabin noise by UHBR engines compared to conventional turbofans at cruise