Oxygen depletion in coastal seas and the effective spawning stock biomass of an exploited fish species

Environmental conditions may have previously underappreciated effects on the reproductive processes of commercially exploited fish populations, for example eastern Baltic cod, that are living at the physiological limits of their distribution. In the Baltic Sea, salinity affects neutral egg buoyancy, which is positively correlated with egg survival, as only water layers away from the oxygen consumption-dominated sea bottom contain sufficient oxygen. Egg buoyancy is positively correlated to female spawner age/size. From observations in the Baltic Sea, a field-based relationship between egg diameter and buoyancy (floating depth) could be established. Hence, based on the age structure of the spawning stock, we quantify the number of effective spawners, which are able to reproduce under ambient hydrographic conditions. For the time period 1993–2010, our results revealed large variations in the horizontal extent of spawning habitat (1000–20 000 km2) and oxygen-dependent egg survival (10–80%). The novel concept of an effective spawning stock biomass takes into account offspring that survive depending on the spawning stock age/size structure, if reproductive success is related to egg buoyancy and the extent of hypoxic areas. Effective spawning stock biomass reflected the role of environmental conditions for Baltic cod recruitment better than the spawning stock biomass alone, highlighting the importance of including environmental information in ecosystem-based management approaches

Application of the daily egg production method to Baltic sprat

Baltic sprat (Sprattus sprattus balticus, Schneider 1908) is a key species in the Baltic Sea ecosystem, where it is the most abundant planktivorous fish. In the present study, we applied the daily egg production method (DEPM) for the years 1999–2008 to estimate the size of the stock component reproducing in the Bornholm Basin, a major spawning ground for sprat and cod. This is the first study assessing this stock with a fishery independent egg production method for a consecutive time series of ten years. DEPM stock size estimates were compared with those obtained by a multi species virtual population analysis for the same stock component and results from an acoustic survey. In general, the results obtained by the DEPM were in the same order of magnitude compared to the other methods and most similar to the acoustic estimate. However, in some years differences between methods were substantial. With respect to previous egg production methods to assess Baltic sprat stock components our approach takes several aspects into account which were ignored before, e.g. effect of ambient temperature range on sprat egg stage duration and mortality and interannual variability of adult stock parameters. Since the accurate determination of the daily spawning fraction bears major uncertainties, different scenarios were tested for this parameter. Least deviation compared to the other assessment methods was obtained when using a daily female spawning fraction of 24%, which corresponds well to values described in literature. The applicability of the DEPM to Baltic sprat was clearly demonstrated. Thus, it can serve as valuable tool for the estimation of Baltic sprat stock sizes independent of data obtained from commercial fisheries

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates

Report on the nature and types of driver interactions including their potential future

The Baltic Sea is a dynamic environment responding to various drivers operating at different temporal and spatial scales. In response to climate change, the Baltic Sea is warming and the frequency of extreme climatic events is increasing (Lima & Wethey 2012, BACC 2008, Poloczanska et al. 2007). Coastal development, human population growth and globalization intensify stressors associated with human activities, such as nutrient loading, fisheries and proliferation of invasive and bloom-forming species. Such abrupt changes have unforeseen consequences for the biodiversity and the function of food webs and may result in loss of ecological key species, alteration and fragmentation of habitats. To mitigate undesired effects on the Baltic ecosystem, an efficient marine management will depend on the understanding of historical and current drivers, i.e. physical and chemical environmental conditions and human activities that precipitate pressures on the natural environment. This task examined a set of key interactions of selected natural and anthropogenic drivers in space and time, identified in Task 3.1 as well as WP1 and WP2 (e.g. physico-chemical features vs climate forcing; eutrophication vs oxygen deficiency vs bio-invasions; fisheries vs climate change impacts) by using overlay-mapping and sensitivity analyses. The benthic ecosystem models developed under Task 2.1 were used to investigate interactions between sea temperature and eutrophication for various depth strata in coastal (P9) and offshore areas (P1) of the Baltic Sea. This also included investigation on how the frequency and magnitude of deep-water inflow events determines volume and variance of salinity and temperature under the halocline, deep-water oxygen levels and sediment fluxes of nutrients, using observations and model results from 1850 to present (P1, P2, P6, P9, P12). The resulting synthesis on the nature and magnitude of different driver interactions will feed into all other tasks of this WP3 and WP2/WP4. Moreover, the results presented in this report improve the process-based and mechanistic understanding of environmental change in the Baltic Sea ecosystem, thereby fostering the implementation of the Marine Strategy Framework Directive

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10−5) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10−5, ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutatio

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

Background and Aims: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). Approach and Results: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) &lt; 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) (p &lt; 0.0001). ALP normalization occurred in 5.4% (p=0.08) and 27.3% (p &lt; 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: −3.14 (p=0.02); placebo: −1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% (p=0.0008); 10 mg: 16.7% (p=0.03); placebo: 4%]. There were no serious treatment-related adverse events. Conclusions: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study

Background and Aims: ENHANCEwas a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and Results: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n= 89), 10 mg (n= 89), placebo (n= 87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) &lt; 1.67xupper limit of normal (ULN), &gt;= 15% ALP decrease from baseline, and total bilirubin &lt;= ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score &gt;= 4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10mg: 78.2%) versus placebo (12.5%) (p &lt; 0.0001). ALP normalization occurred in 5.4% (p= 0.08) and 27.3% (p &lt; 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 (p= 0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% (p= 0.0008); 10 mg: 16.7% (p= 0.03); placebo: 4%]. There were no serious treatment-related adverse events.Conclusions: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated