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Der erste Tagungsband zum Handbuch zur Geschichte der Ökonomie des Alpenraums in präindustrieller Zeit schließt die Lücke einer raumübergreifenden Synopse der alpenländischen Wirtschaftsgeschichte.

Der erste Tagungsband zum Handbuch zur Geschichte der Ökonomie des Alpenraums in präindustrieller Zeit schließt die Lücke einer raumübergreifenden Synopse der alpenländischen Wirtschaftsgeschichte. Renommierte Wissenschaftler untersuchen in drei Bänden den Raum und seine Menschen, den Alltag der Alpenbewohner sowie den Handel, Migration und Kommunikation.

We examine the relationship between inheritance rules and voter turnout. Inheritance rules are measured by entailed farms in South Tyrol: land properties whose inheritance is regulated by a law similar to the right of primogeniture. Using data for municipalities between 1998 and 2010, we show that voter turnout is high in municipalities with many entailed farms relative to population. The effect is based on local elections. If the number of entailed farms per 100 inhabitants increases by one standard deviation, voting turnout in municipal and provincial elections increases by around 1.27 and 1.43 percentage points (around 25 and 35 percent of a standard deviation). Our results suggest that entailed farm owners themselves are more likely to vote, and that entailed farms owners encourage other citizens of their municipality to participate in local elections.

We examine the relationship between inheritance rules and voter turnout. Inheritance rules are measured by entailed farms in South Tyrol: land properties whose inheritance is regulated by a law similar to the right of primogeniture. Using data for municipalities between 1998 and 2010, we show that voter turnout is high in municipalities with many entailed farms relative to population. The effect is based on local elections. If the number of entailed farms per 100 inhabitants increases by one standard deviation, voting turnout in municipal and provincial elections increases by around 1.27 and 1.43 percentage points (around 25 and 35 percent of a standard deviation). Our results suggest that entailed farm owners themselves are more likely to vote, and that entailed farms owners encourage other citizens of their municipality to participate in local elections.

BackgroundMethylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer, MTAP gene copy number loss (MTAP loss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact of MTAP alterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable. Here, we aim to investigate the prevalence, clinicopathological features and prognosis of MTAP loss GI cancers.MethodsCases with MTAP alterations were retrieved from The Cancer Genome Atlas (TCGA) and a real-world cohort of GI cancers profiled by next-generation sequencing. If MTAP alterations other than loss were found, immunohistochemistry was performed. Finally, we set a case–control study to assess MTAP loss prognostic impact.ResultsFindings across the TCGA dataset (N=1363 patients) and our cohort (N=508) were consistent. Gene loss was the most common MTAP alteration (9.4%), mostly co-occurring with CDKN2A/B loss (97.7%). Biliopancreatic and gastro-oesophageal cancers had the highest prevalence of MTAP loss (20.5% and 12.7%, respectively), being mostly microsatellite stable (99.2%). In colorectal cancer, MTAP loss was rare (1.1%), while most MTAP alterations were mutations (5/7, 71.4%); among the latter, only MTAP-CDKN2B truncation led to protein loss, thus potentially actionable. MTAP loss did not confer worse prognosis.Conclusions MTAP alterations are found in 5%–10% of GI cancers, most frequently biliopancreatic and gastro-oesophageal. MTAP loss is the most common alteration, identified almost exclusively in MSS, CDKN2A/B loss, upper-GI cancers. Other MTAP alterations were found in colorectal cancer, but unlikely to cause protein loss and drug susceptibility.

Background Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. Case presentation A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. Conclusions Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.