The control of sea lice in Atlantic salmon by selective breeding

Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production.     

Techniques for high-frequency integrated test and measurement

This paper describes techniques for the on-chip measurement of high-frequency and/or high-bandwidth electrical phenomena in ultra large-scale integration environments. The techniques rely on the integration of multiple compact and robust electronic test devices, or cores, at various locations within an integrated circuit. The cores consist primarily of signal generators that approximate the output of a sigma-delta modulator using finite repetitious bit patterns and a small set of highly robust analog components. They are capable of digitizing on-chip signals at gigahertz rates even using low-cost manufacturing processes. Simple communication between the multiple cores enables the migration of many "board-level" type measurements down to the chip level.     

Confronting mortality: the Iliad''s androktasiai

This article describes the results of a survey of radiography program directors on positioning competencies for entry-level radiographers. The survey asked program directors to classify projections as essential, important, rarely needed or for reference only. The objective of the study was to rank radiographic projections from most to least important in clinical practice. The data are provided for use by educators and employers in determining which projections are essential entry-level competencies.     

Reliability and validity of the measurement of position sense in women with osteoarthritis of the knee

OBJECTIVE: We examined the test-retest reliability and the construct validity of the measurement of knee position sense for describing the functional weightbearing performance of women with osteoarthritis (OA) of the knee. METHODS: For the purpose of this study, position sense was defined as the error occurring when subjects attempted to reproduce a criterion angle in standing with visual cues eliminated. Five such tests were recorded photographically on 3 different occasions. On each occasion the 10 subjects also completed a self-paced walking test over a 13 m indoor walkway. RESULTS: The photographic measurements were reproducible (r = 0.90) and there was no change in positioning accuracy across sessions. There was a significant (p < 0.05) inverse correlation of 0.70 between the standard deviation of the mean individual measurements of position sense (precision of the test) and those of walking speed. CONCLUSION: Our study demonstrates good measurement reliability and a comparable mean angular error with repeated tests. It also suggests the amplitude of the variability of this error is a strong determinant of an individual OA patient's functional performance in walking.     

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury: implications for the derivation of a reference dose

A critical step in the U.S. EPA's derivation of an Reference Dose (RfD) for methylmercury is conversion of the maternal hair Hg concentration of 11 ppm to average daily intake using the one-compartment pharmacokinetic model. A default uncertainty factor (UF) adjustment of 3 for interindividual variability was then applied to this conversion. A probabilistic (Monte Carlo) analysis is presented estimating the interindividual variability inherent in this dose conversion for women 18-40 years old based on data in the scientific literature. The dose of 1.1 micrograms/kg/day, calculated by the U.S. EPA to correspond to 11 ppm Hg in hair, is estimated in this analysis to be larger than 94-99% of corresponding doses. The application of a UF of 3 to this U.S. EPA value gives a dose which is estimated to be larger than 28-73% of corresponding doses. This analysis suggests that if the dose conversion in the RfD is intended to be inclusive of 95-99% of women 18-40, the daily intake should be set at 0.1-0.3 microgram/kg/day. The RfD of 0.03-0.1 microgram/kg/day, derived from this dose by the U.S. EPA's application of an additional UF of 3 for additional toxicologic concerns, is somewhat smaller than the current RfD of 0.1 microgram/kg/day.     

Should acyclovir prophylaxis be used in late pregnancy in women with recurrent genital herpes infection? How to use a clinical decision analysis

Contact stomatitis is rather uncommon because of the relative resistance of the oral mucosa to irritant agents and allergens. The clinical manifestations of contact stomatitis are extremely variable and include erythema, erosions, ulcerations, leukoplakia-like lesions, and lichenoid reactions. Clinical signs are frequently less pronounced than subjective symptoms, and patients commonly experience severe functional problems despite only mild mucosal alterations. Allergic stomatitis is rare and almost always attributable to metallic mercury and gold salts. A careful history and an accurate examination of the oral cavity, teeth, and dental restorations are essential for a correct diagnosis. Patch testing is indicated in all lesions that are not clearly related to trauma or physical injuries. Patch testing is not useful in the burning mouth syndrome. Evaluation of clinical relevance of patch test results is always very difficult and requires an interdisciplinary approach to the patient. Successful treatment requires the identification and elimination of the causative factor, when possible. It is important to bear in mind that replacement of dental restorations and prostheses may be very expensive and stressful for the patient and thus should not be recommended when their causative role is doubtful.     

Treatment of radiation-induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.