Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort.

In aetiologically complex illnesses such as schizophrenia, there is no direct link between genotype and phenotype. Intermediate phenotypes could help clarify the underlying biology and assist in the hunt for genetic vulnerability variants. We have previously shown that cognition shares substantial genetic variance with schizophrenia; however, it is unknown if this reflects pleiotropic effects, direct causality or some shared third factor that links both, for example, brain volume (BV) changes. We quantified the degree of net genetic overlap and tested the direction of causation between schizophrenia liability, brain structure and cognition in a pan-European schizophrenia twin cohort consisting of 1243 members from 626 pairs. Cognitive deficits lie upstream of the liability for schizophrenia with about a quarter of the variance in liability to schizophrenia explained by variation in cognitive function. BV changes lay downstream of schizophrenia liability, with 4% of BV variation explained directly by variation in liability. However, our power to determine the nature of the relationship between BV deviation and schizophrenia liability was more limited. Thus, while there was strong evidence that cognitive impairment is causal to schizophrenia liability, we are not in a position to make a similar statement about the relationship between liability and BV. This is the first study to demonstrate that schizophrenia liability is expressed partially through cognitive deficits. One prediction of the finding that BV changes lie downstream of the disease liability is that the risk loci that influence schizophrenia liability will thereafter influence BV and to a lesser extent. By way of contrast, cognitive function lies upstream of schizophrenia, thus the relevant loci will actually have a larger effect size on cognitive function than on schizophrenia. These are testable predictions.

Computation of individual latent variable scores from data with multiple missingness patterns.

Latent variable models are used in biological and social sciences to investigate characteristics that are not directly measurable. The generation of individual scores of latent variables can simplify subsequent analyses. However, missing measurements in real data complicate the calculation of scores. Missing observations also result in different latent variable scores having different degrees of accuracy which should be taken into account in subsequent analyses. This manuscript presents a publicly available software tool that addresses both these problems, using as an example a dataset consisting of multiple ratings for ADHD symptomatology in children. The program computes latent variable scores with accompanying accuracy indices, under a 'user-specified' structural equation model, in data with missing data patterns. Since structural equation models encompass factor models, it can also be used for calculating factor scores. The program, documentation and a tutorial, containing worked examples and specimen input and output files, is available at http://statgen.iop.kcl.ac.uk/lsc .

Metabolism of the thiocarbamate herbicide SUTAN in rats.

1. The metabolism of the thiocarbamate herbicide SUTAN (butylate) was studied after administration of single oral doses of [isobutyl-1-14C]SUTAN to male and female rats. 2. The radiolabelled dose was rapidly absorbed and excreted, with 79% of the dose excreted in the urine in 72 h. The small percentages of radioactivity excreted in the faeces and as 14CO2 were significantly higher (P less than or equal to 0.05) in males than in females. 3. SUTAN was extensively metabolized, and no unmetabolized SUTAN was found in the urine. A total of 18 of the 29 urinary metabolites were identified, and identified metabolites represented 83-88% of the urinary radioactivity. 4. Diisobutylamine was the major urinary metabolite in both males and females, averaging 51% of the urinary radioactivity. 5. Other significant urinary metabolites included primary hydroxylated and tertiary hydroxylated diisobutylamines and a series of mercapturic acid pathway metabolites, including an S-glucuronide and several hydroxylated and unhydroxylated mercapturates. 6. Oxidations at the three alkyl groups produced a variety of minor urinary metabolites, and hydroxylation of the primary or tertiary carbon on the isobutyl groups, followed by an intramolecular reaction, generated a series of minor cyclized metabolites.

Health effects among refrigeration repair workers exposed to fluorocarbons.

Refrigeration repair workers may be intermittently exposed to fluorocarbons and their thermal decomposition products. A case of peripheral neuropathy (distal axonopathy) in a commercial refrigeration repairman prompted an epidemiological investigation of the health of refrigeration repair workers. No additional cases of peripheral neuropathy were identified among the 27 refrigeration repair workers studied. A reference group of 14 non-refrigeration repair workers was also studied. No differences were noted between groups for the ulnar (motor and sensory), median (motor and sensory), peroneal, sural, or tibial nerve conduction velocities. Refrigeration repair workers reported palpitations and lightheadedness significantly more often than workers in the reference group. No clinical neurological or electroneurophysiological abnormalities were detected in eight refrigeration repair workers followed up for three years during continuous employment.

Progressing toward professionalization: the role of continuing education.

The traditional term professionalism--variously linked to such characteristics as an "organized body of knowledge", or a "closely-knit association of people with a high degree of communication"--has been described recently as a static concept. It is professionalization--the dynamic process of refinement through which the character and spirit of a profession is made real and operative--which is more relevant. Part of that process is quite obviously the application of new knowledge which today is growing at an increasing rate. Note this paradox: that although each profession grows by accentuating its own distinctive knowledge, that very specialization leads in turn to the need for closer relationships with allied professions. Equally important is each profession's need to continue to redefine its relationship with its clients. Continuing education is an essential tool in both of these tasks. Recent studies elicited a variety of reasons for the professional's interest and engagement in continuing education: to become better informed; to gain personal enrichment; to achieve career advancement; to satisfy individual curiosity; to fulfill an employer's requirements; to qualify for licensure; to meet new people; or to break out of a routine. Typically, continuing education is promoted by professional schools, university extension divisions, employing agencies, the professional association itself--and even its commercial suppliers. Physiotherapists ought reasonably to ask themselves these questions: What goals are to be sought in the ensuing five years? Which of these can be met through continuing education? What barriers to continuing education now exist? What methodology and delivery of continuing education will best serve the profession? How can this educational thrust be harnessed to improve physiotherapists' relationships with other professionals--and the general public?

Anterior cervical discectomy without bone graft. Report of 71 cases.

Anterior cervical discectomy without bone grafting may become the procedure of choice for acute cervical disc protrusions. This operation was performed on 71 patients, all of whom were followed from 1 to 6 years. Complications were minor in nature. The results were excellent and sustained.