Overview of the international fishing activities on the Cleaver Bank and Frisian Front : update with Dutch, British, Danish, German, Belgian, Swedish and French data for 2010-2015

In response to a request to Wageningen University & Research from the Dutch Ministry of Economic Affairs an update of the data and analysis on the value of the fishing activities of the Dutch, British, Danish, German, Belgian, Swedish and French fishing fleets on the proposed closed areas on the Cleaver Bank and Frisian Front was prepared. This report uses the method presented in Chapter 5 of ‘Effects of seabed protection on the Frisian Front and Central Oyster Grounds’ (Van Oostenbrugge et al. 2015) to update the reports already published by Wageningen Economic Research on fishing activity on the proposed closed areas on the Cleaver Bank and Frisian Front (Hamon et al. 2013; Oostenbrugge and Hamon 2014). The effort, value and landings by the Dutch, British, Danish, German, Belgian, Swedish and French fishing fleets are presented for a five year period (2010-2015) and show variations over the last years but generally show a decline in effort in both areas. Value of landings and gross value added show an upward trend for the Dutch fishery in the Cleaver Bank (with a low point in 2013) but a downward trend for the British, German and Belgian fleets and for the Frisian Front. Main target species of the Cleaver Bank are plaice, targeted by the beam trawl fleet, followed by mackerel, cod and whiting in the rest of the demersal fleet. On the Frisian Front, gillnets target mainly sole and cod. The total value of landings has remained relatively stable on the Cleaver Bank between €1.6m and €2m over years (with the exception of the low 2013 value at €0.7m) while it remained low for the Frisian Front around €17,000 per year on average for the fleets from the countries considered. Within fleets, the dependency of individuals on the areas to be closed can greatly vary although the value of landings in the proposed closures represent less than 1% of the total value of landings for the Dutch fleet. For the Dutch fisheries about 30 to 40 vessels fish a minor part (less than 10%) of their revenue from the proposed closed areas on the Cleaver Bank and only 1 or 2 vessels get more than 10% of their revenue from the proposed closures. Between 15 and 20 vessels would be impacted by a seasonal closure on the Frisian Front net fishery, of those vessels only one fished more than 10% of its revenue in the proposed closure for one year

Terminal-repeat retrotransposons with GAG domain in plant genomes : a new testimony on the complex world of transposable elements

A novel structure of nonautonomous long terminal repeat (LTR) retrotransposons called terminal repeat with GAG domain (TR-GAG) has been described in plants, both in monocotyledonous, dicotyledonous and basal angiosperm genomes. TR-GAGs are relatively short elements in length (<4 kb) showing the typical features of LTR-retrotransposons. However, they carry only one open reading frame coding for the GAG precursor protein involved for instance in transposition, the assembly, and the packaging of the element into the virus-like particle. GAG precursors show similarities with both Copia and Gypsy GAG proteins, suggesting evolutionary relationships of TR-GAG elements with both families. Despite the lack of the enzymatic machinery required for their mobility, strong evidences suggest that TR-GAGs are still active. TR-GAGs represent ubiquitous nonautonomous structures that could be involved in the molecular diversities of plant genomes

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)

EFFICACY OF ALIROCUMAB IN 1,191 PATIENTS WITH A WIDE SPECTRUM OF MUTATIONS IN GENES CAUSATIVE FOR FAMILIAL HYPERCHOLESTEROLEMIA

Background Mutation(s) in genes involved in the low-density lipoprotein receptor (LDLR) pathway are typically the underlying cause of familial hypercholesterolemia. Objective The objective of the study was to examine the influence of genotype on treatment responses with alirocumab. Methods Patients from 6 trials (n = 1191, including 758 alirocumab-treated; Clinicaltrials.gov identifiers: NCT01266876; NCT01507831; NCT01623115; NCT01709500; NCT01617655; NCT01709513) were sequenced for mutations in LDLR , apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), LDLR adaptor protein 1, and signal-transducing adaptor protein 1 genes. New mutations were confirmed by Sanger sequencing. Results One or more specific gene mutations were found in 898 patients (75%): 387 and 437 patients had heterozygous LDLR defective and negative mutations, respectively; 46 had a heterozygous APOB -defective mutation; 8 patients had a heterozygous PCSK9 gain-of-function mutation; 293 (25%) had no identifiable mutation in the genes investigated. LDL cholesterol reductions at Week 24 were generally similar across genotypes: 48.3% (n = 131) and 54.3% (n = 89) in LDLR -defective heterozygotes with alirocumab 75 mg Q2W (with possible increase to 150 mg at Week 12) and 150 mg Q2W, respectively; 49.7% (n = 168) and 60.7% (n = 88) in LDLR -negative heterozygotes; 54.1% (n = 20) and 50.1% (n = 6) in APOB -defective heterozygotes; 60.5% (n = 5) and 94.0% (n = 1) in PCSK9 heterozygotes; and 44.9% (n = 85) and 55.4% (n = 69) in patients with no identified mutations. Overall rates of treatment-emergent adverse events were similar for alirocumab vs controls (placebo in 5 trials, ezetimibe control or atorvastatin calibrator arm in 1 trial), with only a higher rate of injection-site reactions with alirocumab. Conclusions In this large patient cohort, individuals with a wide spectrum of mutations in genes underlying familial hypercholesterolemia responded substantially and similarly to alirocumab treatment

Alirocumab efficacy in patients with double heterozygous, compound heterozygous, or homozygous familial hypercholesterolemia

Background Mutations in the genes for the low-density lipoprotein receptor ( LDLR ), apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 have been reported to cause heterozygous and homozygous familial hypercholesterolemia (FH). Objective The objective is to examine the influence of double heterozygous, compound heterozygous, or homozygous mutations underlying FH on the efficacy of alirocumab. Methods Patients from 6 alirocumab trials with elevated low-density lipoprotein cholesterol (LDL-C) and FH diagnosis were sequenced for mutations in the LDLR , apolipoprotein B, proprotein convertase subtilisin/kexin type 9, LDLR adaptor protein 1 ( LDLRAP1 ), and signal-transducing adaptor protein 1 genes. The efficacy of alirocumab was examined in patients who had double heterozygous, compound heterozygous, or homozygous mutations. Results Of 1191 patients sequenced, 20 patients were double heterozygotes (n = 7), compound heterozygotes (n = 10), or homozygotes (n = 3). Mean baseline LDL-C levels were similar between patients treated with alirocumab (n = 11; 198 mg/dL) vs placebo (n = 9; 189 mg/dL). All patients treated with alirocumab 75/150 or 150 mg every 2 weeks had an LDL-C reduction of ≥15% at either week 12 or 24. At week 12, 1 patient had an increase of 7.1% in LDL-C, whereas in others, LDL-C was reduced by 21.7% to 63.9% (corresponding to 39–114 mg/dL absolute reduction from baseline). At week 24, LDL-C was reduced in all patients by 8.8% to 65.1% (10–165 mg/dL absolute reduction from baseline). Alirocumab was generally well tolerated in the 6 trials. Conclusion Clinically meaningful LDL-C–lowering activity was observed in patients receiving alirocumab who were double heterozygous, compound heterozygous, or homozygous for genes that are causative for FH

Radionuclide Migration Experiments in Tuff Blocks/Underunsaturated and Saturated Conditions at a Scale of Up to 1 Metre

To complement migration experiments with non-radioactive tracers in the Busted Butte experimental facility (BBTF) at the Nevada Test Site, an exploratory migration experiment has been performed under unsaturated conditions in a {approx}0.3m x {approx}0.3m x {approx}0.3m block of tuff. Longer term migration experiments, up to 600 days, under unsaturated and saturated conditions in {approx}1 m3 blocks of tuff have recently been completed. Na-fluorescein, 3H (as tritiated water), 22Na, 60Co, 95mTc and/or 99Tc (as the pertechnetate anion), 137Cs, and 237Np were used as tracers in all three experiments. Under unsaturated conditions, Tc is transported slightly faster than 3H, while under saturated conditions, the chemical conditions became highly reducing, leading to significant retardation of Tc along the flow field. If chemically reducing conditions can be demonstrated to exist in the saturated zone downstream from the proposed repository, the geological formations underlying the proposed repository horizon can potentially act as a geological barrier to the transport of some multivalent radionuclides