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Background: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue.Summary: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12‑lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit.Conclusion: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular. [ABSTRACT FROM AUTHOR]

Common loons ( Gavia immer ) staging on the Great Lakes during fall migration are at risk to episodic outbreaks of type E botulism. Information on distribution, foraging patterns, and exposure routes of loons are needed for understanding the physical and ecological factors that contribute to avian botulism outbreaks. Aerial surveys were conducted to document the spatiotemporal distribution of common loons on Lake Michigan during falls 2011–2013. In addition, satellite telemetry and archival geolocator tags were used to determine the distribution and foraging patterns of individual common loons while using Lake Michigan during fall migration. Common loon distribution observed during aerial surveys and movements of individual radiomarked and/or geotagged loons suggest a seasonal pattern of use, with early fall use of Green Bay and northern Lake Michigan followed by a shift in distribution to southern Lake Michigan before moving on to wintering areas. Common loons tended to occupy offshore areas of Lake Michigan and, on average, spent the majority of daylight hours foraging. Dive depths were as deep as 60 m and dive characteristics suggested that loons were primarily foraging on benthic prey. A recent study concluded that round gobies ( Neogobius melanostomus ) are an important prey item of common loons and may be involved in transmission of botulinum neurotoxin type E. Loon distribution coincides with the distribution of dreissenid mussel biomass, an important food resource for round gobies. Our observations support speculation that energy transfer to higher trophic levels via gobies may occur in deep-water habitats, along with transfer of botulinum neurotoxin. [ABSTRACT FROM AUTHOR]

Specific alkylators may allow synthetic lethality among patients with germline BRCA1/2 -mutations related cancers. The tetrahydroisoquinolone trabectedin administered at 1.3 mg/m 2 as a 3-h intravenous infusion every 3 weeks showed activity in patients with pretreated metastatic breast cancer (MBC) and BRCA germline mutations, but mainly in BRCA2 carriers. Data from a phase II study were retrospectively analyzed to compare the efficacy and safety of this trabectedin dose and schedule in pretreated MBC patients bearing germline BRCA1/2 mutations. The primary efficacy endpoint was the objective response rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST) by independent expert review. Duration of response (DR) and progression-free survival (PFS) were secondary efficacy endpoints. Safety was evaluated using the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Data from 26 BRCA1 -mutated and 13 BRCA2 -mutated patients were analyzed. 69% of BRCA1 -mutated cancers were triple-negative vs. 31% of BRCA2 -mutated ones. 77% of BRCA1 and 31% of BRCA2 carriers were platinum-pretreated. The ORR in BRCA2 -mutated patients was higher than in BRCA1 -mutated patients (33.3% vs. 9.1%). DR ranged for 1.4–6.8 months in BRCA2 -mutated patients and for 1.5–1.7 months in BRCA1 -mutated patients. More BRCA2 -mutated patients had disease stabilization for ≥4 months (25.0% vs. 9.1%) and their median PFS was longer (4.7 vs. 2.5 months). Trabectedin was well tolerated in both patient subtypes. In conclusion, t rabectedin showed higher antitumor activity in relapsed MBC patients with germline BRCA2 mutations than in those with BRCA1 mutations. [ABSTRACT FROM AUTHOR]

Avian botulism type E is responsible for extensive waterbird mortality on the Great Lakes, yet the actual site of toxin exposure remains unclear. Beached carcasses are often used to describe the spatial aspects of botulism mortality outbreaks, but lack specificity of offshore toxin source locations. We detail methodology for developing a neural network model used for predicting waterbird carcass motions in response to wind, wave, and current forcing, in lieu of a complex analytical relationship. This empirically trained model uses current velocity, wind velocity, significant wave height, and wave peak period in Lake Michigan simulated by the Great Lakes Coastal Forecasting System. A detailed procedure is further developed to use the model for back-tracing waterbird carcasses found on beaches in various parts of Lake Michigan, which was validated using drift data for radiomarked common loon ( Gavia immer ) carcasses deployed at a variety of locations in northern Lake Michigan during September and October of 2013. The back-tracing model was further used on 22 non-radiomarked common loon carcasses found along the shoreline of northern Lake Michigan in October and November of 2012. The model-estimated origins of those cases pointed to some common source locations offshore that coincide with concentrations of common loons observed during aerial surveys. The neural network source tracking model provides a promising approach for identifying locations of botulinum neurotoxin type E intoxication and, in turn, contributes to developing an understanding of the dynamics of toxin production and possible trophic transfer pathways. [ABSTRACT FROM AUTHOR]

Abstract: Do family firms rise and decline in three generations? Not only since Thomas Mann''s “The Buddenbrooks” has the survival rate of family firms intrigued family business scholars, practitioners and consultants. In this article, we trace the family firm survival rate to its roots and discuss its empirical basis and univocal reading. We then ask how the mortality of family businesses could be measured, and which contextual factors need to be taken into account. To this end we explore the literature on firm demography, a field which is particularly concerned with age and mortality, and identify crossroads with family business studies. We conclude by suggesting a re-conceptualization of survival rates within a larger firm demographic research framework. [Copyright &y& Elsevier]

Abstract: Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrolment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70–0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71–1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation. [Copyright &y& Elsevier]