Getting priorities straight: Risk assessment and decision-making in the improvement of inherited disorders in pedigree dogs

The issue of inherited disorders in pedigree dogs is not a recent phenomenon and reports of suspected genetic defects associated with breeding practices date back to Charles Darwin's time. In recent years, much information on the array of inherited defects has been assimilated and the true extent of the problem has come to light. Historically, the direction of research funding in the field of canine genetic disease has been largely influenced by the potential transferability of findings to human medicine, economic benefit and importance of dogs for working purposes. More recently, the argument for a more canine welfare-orientated approach has been made, targeting research efforts at the alleviation of the most suffering in the greatest number of animals.

Leisure goods, education attainment and fertility choice

This paper proposes a novel mechanism for the fertility decline that occurred across the world since the late nineteenth century. It suggests that the rise in the cost of children relative to leisure goods in the process of development contributed to the decline in fertility. The paper develops a unified growth model in which children are substitutes for leisure goods in the parental utility function. The theory suggests that the rise in income, the decline in the relative price of leisure goods and the increase in educational attainment in the process of development speed up the demographic transition from high to low fertility and contributed to the transition from stagnation to growth.

Design and evaluation of tinnitus synthesis methods: From spectral to spatial matching

Purpose
This study was designed to investigate methods to help patients suffering from unilateral tinnitus synthesizing an auditory replica of their tinnitus.

Materials and methods
Two semi-automatic methods (A and B) derived from the auditory threshold of the patient and a method (C) combining a pure tone and a narrow band-pass noise centred on an adjustable frequency were devised and rated on their likeness over two test sessions. A third test evaluated the stability over time of the synthesized tinnitus replica built with method C, and its proneness to merge with the patient's tinnitus. Patients were then asked to try and control the lateralisation of this single percept through the adjustment of the tinnitus replica level.

Results
The first two tests showed that seven out of ten patients chose the tinnitus replica built with method C as their preferred one. The third test, performed on twelve patients, revealed pitch tuning was rather stable over a week interval. It showed that eight patients were able to consistently match the central frequency of the synthesized tinnitus (presented to the contralateral ear) to their own tinnitus, which leaded to a unique tinnitus percept. The lateralisation displacement was consistent across patients and revealed an average range of 29dB to obtain a full lateral shift from the ipsilateral to the contralateral side.

Conclusions
Although spectrally simpler than the semi-automatic methods, method C could replicate patients' tinnitus, to some extent. When a unique percept between synthesized tinnitus and patients' tinnitus arose, lateralisation of this percept was achieved.

Production and Evaluation of Antibodies and Phage Display-Derived Peptide Ligands for Immunomagnetic Separation of Mycobacterium bovis

This study describes the development and optimization of an immunomagnetic separation (IMS) method to isolate Mycobacterium bovis cells from lymph node tissues. Gamma-irradiated whole M. bovis AF2122/97 cells and ethanol-extracted surface antigens of such cells were used to produce M. bovis-speci?c polyclonal and monoclonal antibodies in rabbits and mice. They were also used to generate M. bovis-speci?c peptide ligands by phage display biopanning. The various antibodies and peptide ligands obtained were used to coat MyOne tosyl-activated Dynabeads (Life Technologies), singly or in combination, and evaluated for IMS. Initially, M. bovis capture from Middlebrook 7H9 broth suspensions (concentration range, 10 to 10⁵ CFU/ml) was evaluated by IMS combined with an M. bovis-speci?c touchdown PCR. IMS-PCR results and, subsequently, IMS-culture results indicated that the beads with greatest immunocapture capability for M. bovis in broth were those coated simultaneously with a monoclonal antibody and a biotinylated 12-mer peptide. These dually coated beads exhibited minimal capture (mean of 0.36% recovery) of 12 other Mycobacterium spp. occasionally encountered in veterinary tuberculosis (TB) diagnostic laboratories. When the optimized IMS method was applied to various M. bovis-spiked lymph node matrices, it demonstrated excellent detection sensitivities (50% limits of detection of 3.16 and 57.7 CFU/ml of lymph node tissue homogenate for IMS-PCR and IMS-culture, respectively). The optimized IMS method therefore has the potential to improve isolation of M. bovis from lymph nodes and hence the diagnosis of bovine tuberculosis.

Comparison and evaluation of the specificity and binding capacity of commercial and in house affinity columns used in sample preparation for analysis of growth-promoting drugs

Immunoaffinity chromatography (IAC) and affinity chromatography (AC:) are widely used for extraction of drugs from biological samples. Fifteen column types were purchased from five different manufacturers and;their ability to bind specific drugs including beta-agonists and anabolic steroids over a range of analyte concentrations in fortified bovine urine samples was assessed. The performance data obtained from these columns were compared with columns produced in this laboratory (in house columns). The in house columns gave the highest recoveries, ranging from 92 to 100% at the 1 ng spiking concentration, for five of the seven analytes assessed. Forty percent (11 of 27) of all the commercial column assessments recorded recoveries of less than 50% even when the lowest spiking concentration was applied (1 ng). For one manufacturer, only one of seven different columns purchased delivered extraction efficiencies greater than 50%. The extraction efficiencies of the clenbuterol columns were the highest with all commercially prepared columns showing at least 50% binding of radiolabelled tracer. Recoveries of alpha-nortestosterone were the lowest. The variability of these products with respect to quality control requires constant monitoring.