Blue City Mannheim Innovative Konzepte für Konversionsflächen in Mannheim

Im Rahmen der Konversion von 510 ha US-Militärflächen entsteht für die Stadt Mannheim die Chance Zukunftsthemen der Stadtentwicklung intensiv aufzugreifen. Stadterneuerung, Energieeffizienz, Infrastruktur und Mobilität sowie Innovationen und Entfaltungsmöglichkeiten heimischer Unternehmen stehen hierbei gleichermaßen im Fokus. Zur Entwicklung innovativer Ansätze wurde die AG Ingenieursmeile gebildet, in der Themen wie Neue Mobilität, Elektromobilität und Smart Grids herausgearbeitet wurden. Für die Weiterentwicklung und Integration dieser Ansätze hat der Fachbereich Wirtschafts- und Strukturförderung der Stadt Mannheim das themenübergreifende Konzept von MVV Enamic Regioplan erarbeiten lassen. Der Schwerpunkt des Konzeptes „Blue City Mannheim“ liegt auf der Ableitung konkreter Maßnahmen, die in den nächsten Jahren schrittweise umgesetzt werden sollen. Ein wesentliches Ziel ist die Reduktion der CO2-Emissionen im Verkehrssektor durch den Einsatz emissionsarmer (Elektro-) Fahrzeuge und die Umgestaltung des Modal Split. Die Maßnahmen wurden mit den strategischen Zielen der Stadt Mannheim, der wirtschaftspolitischen Strategie und den Anforderungen der Klimaschutzkonzeption 2020 abgestimmt. Als Grundlage werden zunächst vier übergeordnete Maßnahmen definiert: • Vernetzung / Öffentlichkeitsarbeit, • Masterplan Ladeinfrastruktur, • Masterplan Green Logistik sowie • Masterplan blue_village_franklin. Hierauf bauen 21 Einzelmaßnahmen in den Bereichen Fahrzeuge / Fuhrparks, Logistik, Verlagerung Modal Split, Intelligente Netze, Ladeinfrastruktur und Wissenstransfer auf. Als Einzelmaßnahmen werden beispielsweise Einsatzbereiche für emissionsarme Fahrzeuge bei der Umstellung von Fuhrparks und Flotten aufgezeigt. Im Bereich Logistik steht der innerstädtischen Liefer- und Güterverkehr im Mittelpunkt. Maßnahmen betreffen hier z.B. die Umstellung von innerstädtischen Transportverkehren auf Elektrofahrzeuge. Ziel hierbei ist neben der Einsparung von CO2-Emissionen insbesondere auch eine Verkehrslärmreduzierung im Stadtgebiet. Für eine Umgestaltung des Modal Split wird die Verknüpfung von Motorisiertem Individualverkehr (MIV) und ÖPNV an attraktiven Umsteigestationen vorgesehen. Weitere Maßnahmenschwerpunkte liegen in den Bereichen Energieerzeugung, speicherung und -verteilung, durch welche die Umweltpotenziale der Elektromobilität erst vollständig aktiviert werden können. Eine Optimierung von Verbrauch und Erzeugung erfolgt durch Einsatz von IT-Lösungen in intelligenten Netzen (Smart Grids). Maßnahmen für den Ausbau von Ladeinfrastrukturen im gesamten Stadtgebiet sowie die Einrichtung von Multi-System-Tankstellen für unterschiedliche Antriebstechniken ergänzen das Gesamtkonzept. Für den Wissenstransfer und für die öffentliche Wahrnehmung sollen Fachtagungen und Kongresse zu Themen der Neuen Mobilität und der Energieeffizienz durchgeführt werden. Der Maßnahmenkatalog ist nicht abschließend und kann bei Bedarf um weitere Maßnahmen ergänzt werden. Als Akteure für die Umsetzung dieser Maßnahmen sind sowohl Fachbereiche und Betriebe der Stadt Mannheim als auch Mannheimer Unternehmen, Einzelhandel und Handwerk angesprochen. Weiterhin werden die Mannheimer Hochschulen ebenso wie Verbände, die Kammern bis hin zu Privatpersonen in die Umsetzung einbezogen

Breast cancer risk inBRCA1/2mutation carriers and noncarriers under prospective intensified surveillance

Comparably little is known about breast cancer (BC) risks in women from families tested negative forBRCA1/2mutations despite an indicative family history, as opposed toBRCA1/2mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers ofBRCA1/2mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n= 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n= 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) forBRCA1mutation carriers, 43.2% (95% CI 32.1-56.3%) forBRCA2mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) forBRCA1mutation carriers, 13.5 (95% CI 9.2-19.1) forBRCA2mutation carriers and 4.9 (95% CI 3.8-6.3) forBRCA1/2noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) forBRCA1mutation carriers, 6.6% (95% CI 3.4-12.5%) forBRCA2mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women fromBRCA1/2negative families with elevated risk

BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer

Background: Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. Methods: To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. Results: BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95% confidence interval (CI) = 12.02-36.57, P < 0.0001) and in the subgroup of index patients with late-onset OC (OR = 29.91, 95% CI = 14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR = 1.81 95% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. Conclusions: To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer

Purpose To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. Results A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5 (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9 parts per thousand (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. Conclusions High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients

Additional file 1: Table S1. of BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer

Inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for BRCA1 and BRCA2 germline testing. Table S2. Heterozygous protein-truncating mutations identified in the BRIP1 gene. Figure S1. Characterization of the c.507G > A variant within the BRIP1 gene (rs876660937) on transcript level. Table S3. Genotypes and phenotypes of heterozygous BRIP1 mutation carriers identified within the BC/OC index patient cohorts. Table S4. Potentially damaging missense variants identified in the BRIP1 gene. (PDF 215 kb

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer

Chernobyl Accident : Assessing the Data

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10(-8) with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer