Use of deterministic sampling for exploring likelihoods in linkage analysis for quantitative traits

Deterministic sampling was used to numerically evaluate the expected log-likelihood surfaces of QTL-marker linkage models in large pedigrees with simple structures. By calculating the expected values of likelihoods, questions of power of experimental designs, bias in parameter estimates, approximate lower-bound standard errors of estimates and correlations among estimates, and suitability of statistical models were addressed. Examples illustrated that bracket markers around the QTL approximately halved the standard error of the recombination fraction between the QTL and the marker, although they did not affect the standard error of the QTL's effect, that overestimation of the distance between the markers caused overestimation of the distance between the QTL and marker, that more parameters in the model did not affect the accuracy of parameter estimates, that there was a moderate positive correlation between the estimates of the QTL effect and its recombination distance from the marker, and that selective genotyping did not introduce bias into the estimates of the parameters. The method is suggested as a useful tool for exploring the power and accuracy of QTL linkage experiments, and the value of alternative statistical models, whenever the likelihood of the model can be written explictly.     

Effects of three tapering techniques on the performance, forces and psychometric measures of competitive swimmers

The 100-m and 400-m swim time, tethered swimming forces, mood states and self-ratings of well-being of 27 competitive swimmers were measured before and after 4 weeks of intense training and after 1 week and 2 weeks of tapering for major competition. The swimmers were divided into three groups. Each group completed one of three taper regimes similar to those currently performed by swimmers in preparation for competition: (a) reduced training frequency according to each athlete's daily ratings of well-being, (b) reduced training volume, and (c) reduced training volume and intensity. Significant improvements in the Profile of Mood States measures of tension, depression and anger (P < 0.05) were observed after 1 week of tapering, with significant improvements in total mood disturbance and fatigue (P < 0.05) and peak tethered swimming force (P < 0.01) after 2 weeks. Non-significant improvements in 100-m and 400-m swim time (P > 0.05) were observed and no significant differences were revealed among the three tapering techniques. These data highlighted the importance of providing sufficient recovery before competition, since 1 week of reduced training was not long enough to maximise the benefits of tapering. However, none of the three types of tapering currently used by competitive swimmers could be shown to be more beneficial than the others. Accepted: 9 February 1998     

The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: I. Histologic and electrophysiologic assessment.

Nerve regeneration across peripheral nerve allografts and control autografts in primates immunosuppressed with Cyclosporin A was quantitatively evaluated by electrophysiologic and histologic methods. Twelve cynomolgus monkeys received 3-cm autografts and allografts in contralateral ulnar nerves. They were immunosuppressed with Cyclosporin A at 25 mg/kg per day or placebo vehicle. Morphometric analysis of nerve graft and distal nerve segments was assessed at 1 year after engraftment. Quantitative electrophysiologic studies were performed percutaneously at 6 and 12 months, and compound action potentials were measured directly across the nerve grafts at 1 year. Excellent regeneration was seen across autografts and allografts in Cyclosporin A-treated and placebo-treated recipients.     

Analysis of the human Ig isotype response to lactoferrin binding protein A from Neisseria meningitidis

An effective vaccine for serogroup B meningococci has yet to be developed and attention has turned to subcapsular antigens of the meningococcus as possible vaccine candidates. Iron binding proteins are being studied, with most interest focused on the transferrin binding proteins (TbpA and TbpB) and the ferric binding protein (FbpA). This study describes the purification of lactoferrin binding protein A (LbpA) from two meningococcal strains and assesses the human isotype-specific serum antibody response to these proteins in patients with proven meningococcal disease due to a range of phenotypes. Overall, fewer than 50% of sera contained IgG that recognised LbpA isolated from either strain and this antibody response was not uniform between the two proteins. There was some evidence that the antibody response varied between meningococcal phenotypes. This study demonstrates that LbpA does not induce a highly cross-reactive antibody response, indicating that it is unlikely to be an effective vaccine antigen.     

Avoiding biohazards in medical, veterinary and research laboratories

Personnel in medical, veterinary or research laboratories may be exposed to a wide variety of pathogens that range from deadly to debilitating. For some of these pathogens, no treatment is available, and in other cases the treatment does not fully control the disease. It is important that personnel in laboratories that process human or microbiological specimens follow universal precautions when handling tissues, cells, or microbiological specimens owing to the increasing numbers of individuals infected with hepatitis C and HIV in the US and the possibility that an individual may be asymptomatic when a specimen is obtained. Similar precautions must be followed in laboratories that use animal tissues owing to the possibility of exposure to agents that are pathogenic in humans. Personnel with conditions associated with immunosuppression should evaluate carefully whether or not specific laboratory environments put them at increased risk of disease. We offer here some general approaches to identifying biohazards and to minimizing the potential risk of exposure. The issues discussed can be used to develop a general safety program as required by regulatory or accrediting agencies, including the Occupational Safety and Health Administration.