Confidence in assessing the effectiveness of bath treatments for the control of sea lice on Norwegian salmon farms

The salmon louse Lepeophtheirus salmonis is the most important ectoparasite of farmed salmonids in the Northern hemisphere, having a major economic and ecological impact on the sustainability of this sector of the aquaculture industry. To a large extent, control of L. salmonis relies on the use of topical delousing chemical treatments in the form of baths. Improvements in methods for the administration and assessment of bathtreatments have not kept pace with the rapid modernization and intensification of the salmon industry. Bathtreatments present technical and biological challenges, including best practice methods for the estimation of the effect of licetreatment interventions. In this communication, we compare and contrast methods to calculate and interpret treatmenteffectiveness at pen and site level. The methods are illustrated for the calculation of the percentage reduction in mean abundance of mobile lice with a measure of confidence. Six different methods for the calculation of confidence intervals across different probability levels were compared. We found the quasi-Poisson method with a 90% confidence interval to be informative and robust for the measurement of bathtreatment performance

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Counting sea lice on Atlantic salmon farms : empirical and theoretical observations

This communication briefly reviews some of the factors which have shaped the current protocols for lice counting on salmon farms and points out that the motivation for counting is not always the same. It is also apparent that a number of widely accepted assumptions, such as those relating to presumed lice population distributions or the ability to pre-select highly infested cages, cannot be uncritically accepted. Recent research from Scotland, Norway and Canada has demonstrated that the fish on farm sites are clustered in cages which have significant differences in lice abundance. Moreover, the prevalence and distribution of lice in farmed and wild fish populations have distinct patterns. At low prevalence the distributions can be described by the negative binomial distribution, whereas at high prevalence lice tend to be normally distributed. The monitoring strategy of sampling the most infested cage on a farm for early detection of a breach of treatment trigger levels for lice is flawed. These findings need to be taken into account when sampling protocols for lice are designed. In particular, precision in estimating prevalence and abundance of lice on the site requires random sampling from many cages. There is no evidence of systematic bias rising from the use of farm staff counting sea lice compared with dedicated counting teams

Use of a mathematical model to describe the epidemiology of Lepeophtheirus salmonis on farmed Atlantic salmon Salmo salar in the Hardangerfjord, Norway

abstract: Infestation patterns of the sea louse Lepeophtheirus salmonis from 44 salmon farms in the Hardangerfjord on the south-west coast of Norway over the period 2004 to 2007 were assimilated to create 20-month production cycle profiles for spring and autumn stocked generations. The timing and frequency of in-feed and bath treatments to control sea lice associated with these profiles was considered. Spring and autumn stocked farms were observed to have different patterns of sea lice counts on salmon during the first and second years of production. Spring stocked sites experienced increasing infestation toward the end of the first year and on average counts remained elevated thereafter, whereas autumn stocked sites averaged lower sea lice counts throughout most of the production cycle until the latter part of the second year when these escalated rapidly. In-feed treatments were the predominant form of sea lice control in the first half of the production cycle on spring stocked farms, whereas bath treatments were used exclusively in the second half of the production cycle; a very similar pattern of therapeutant use was observed on autumn stocked farms. Results using the SLiDESim (Sea Lice Difference Equation Simulation) infection model and a range of biological and production parameters showed that modelling resulted in a better fit to the mobile lice profiles for autumn stocked farms compared to spring stocked farms. Some features of the mobile lice profiles were not captured by the infection model such as the oscillation of the population between months 11 and 18 of the production cycle on spring stocked farms, and a large peak observed in month 19 on autumn stocked farms. Before modelling can be used to evaluate optimal treatment strategies or other management interventions there remains a need to more clearly understand the underlying biological processes associated with the dynamics of sea lice infestations in the Hardangerfjord

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog.

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI). Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements of hemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24 h period. Hemodynamic measurements revealed a > 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid (PA). GTP inhibition of (PA)-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showed an increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria