Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies.

Platelet glycoprotein Ia* is the processed form of multimerin--isolation and determination of N-terminal sequences of stored and released forms

Glycoprotein Ia* (GPIa*), a very high molecular mass, platelet alpha-granule protein consisting of 167 kDa subunits disulphide-linked in a multimeric structure, was first described by Bienz and Clemetson in 1989 (J. Biol. Chem. 264, 507-514). In 1991 Hayward et al. (J. Biol. Chem. 266, 7114-7120) independently identified a platelet protein with multimeric structure. Despite strong similarities to GPIa* they concluded that it was a novel multimeric protein and named it first p-155 and later, multimerin. Multimerin has also been found in endothelial cells and has been cloned recently from an endothelial cell cDNA library. This has made it possible for us to clarify the relationship between GPIa* and multimerin. GPIa* was isolated from platelet releasate and the N-terminal sequence of 167 kDa and 155 kDa subunit species were determined. The N-terminal 15 amino acids of GPIa* were identical to the deduced amino acids 184-198 of endothelial multimerin. The N-terminal sequence of the 155 kDa protein was identical to the deduced amino acids 318-326 of multimerin. Thus, platelet GPIa* (167 kDa) is the main processed form of multimerin stored in platelet alpha-granules. The GPIa*/processed multimerin (167 kDa) still contains an RGDS sequence near its N-terminus as well as an EGF domain which may be involved in binding to the platelet surface after release. This sequence and domain are cleaved off in the p-155 form, described earlier as platelet multimerin, which is probably formed after release from alpha-granules.

Dimensions of impulsive behavior in adolescents: laboratory behavioral assessments

Impulsivity is a multifaceted construct that defines a range of maladaptive behavioral styles. The present research aimed to identify different dimensions of impulsive behavior in adolescents from a battery of laboratory behavioral assessments. In one analysis, correlations were examined between two self report and seven laboratory behavioral measures of impulsivity. The correlation between the two self report measures was high compared to correlations between the self report and laboratory behavioral measures. In a second analysis, a principal components analysis was performed with just the laboratory behavioral measures. Three behavioral dimensions were identified -- "impulsive decision-making", "impulsive inattention", and "impulsive disinhibition". These dimensions were further evaluated using the same sample with a confirmatory factor analysis, which did support the hypothesis that these are significant and independent dimensions of impulsivity. This research indicates there are at least three separate subtypes of impulsive behavior when using laboratory behavioral assessments with adolescent participants.

Impact of intraoperative behavior on surgical site infections

BACKGROUND: The aim of this study was to identify intraoperative risk factors for surgical site infections (SSIs), which are accessible to interventions. We evaluated the effect of extensive intraoperative antiseptic measures and the impact of the behavior of members of the surgical team on SSIs. METHODS: Standard versus extensive antiseptic measures were randomly assigned in 1,032 surgical patients. The adherence to principles of asepsis by members of the surgical team was assessed prospectively. RESULTS: The rate of SSI was 14% with standard antiseptic measures and 15% with extensive measures (P = .581). Multivariate analysis identified following independent risk factors: lapses in discipline (odds ratio [OR] 2.02, confidence interval [CI] 1.05-3.88), intestinal anastomosis (OR 6.74, CI 3.42-13.30), duration of operation more than 3 hours (OR 3.34, CI 1.82-6.14), and body mass index >30 kg/m2 (OR 1.98, CI 1.22-3.20). CONCLUSION: Extensive measures of antisepsis did not reduce the incidence of SSI. A lapse to adhere to principles of asepsis was identified as an independent risk factor for the development of SSI (ClinicalTrials.gov number, NCT00555815).

Complete genome sequences of both biotypes of a virus pair of bovine viral diarrhea virus subgenotype 1k

We determined the complete genome sequences of both biotypes of a virus pair of bovine viral diarrhea virus (BVDV) subgenotype 1k. The viruses were isolated from a persistently infected calf suffering from mucosal disease. Compared to the noncytopathic biotype, the cytopathic biotype contains an insertion of 84 nucleotides and 22 nucleotide changes.

Disorganization and timing of motor behavior : insight from gesture impairments and movement patterns in schizophrenia

Background: Motor symptoms are frequent phenomena across the entire course of schizophrenia1. Some have argued that disorganized behavior was associated with aberrant motor behavior. We have studied the association of motor disturbances and disorganization in two projects focusing on the timing of movements. Method: In two studies, we assessed motor behavior and psychopathology. The first study applied a validated test of upper limb apraxia in 30 schizophrenia patients2,3. We used standardized video assessments of hand gestures by a blinded rater. The second study tested the stability of movement patterns using time series analysis in actigraphy data of 100 schizophrenia patients4. Both stability of movement patterns and the overall amount of movement were calculated from data of two hours with high degrees of social interaction comparable across the 100 subjects. Results: In total, 67% of the patients had gesture performance deficits3. Most frequently, they made spatial, temporal and body-part-as-object errors. Gesture performance relied on frontal lobe function2. Poor gesture performance was associated with increased disorganization scores. In the second study, we found disorganization to be predicted only by more irregular movement patterns irrespective of the overall amount of movement4. Conclusion : Both studies provide evidence for a link between aberrant timing of motor behavior and disorganization. Disturbed movement control seems critical for disorganized behavior in schizophrenia.