Blastocyst genotyping for quality control of mouse mutant archives: an ethical and economical approach.

With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects.

A comparison of mental state examination documentation by junior clinicians in electronic health records before and after the introduction of a semi-structured assessment template (OPCRIT+).

OBJECTIVES: The mental state examination (MSE) provides crucial information for healthcare professionals in the assessment and treatment of psychiatric patients as well as potentially providing valuable data for mental health researchers accessing electronic health records (EHRs). We wished to establish if improvements could be achieved in the documenting of MSEs by junior doctors within a large United Kingdom mental health trust following the introduction of an EHR based semi-structured MSE assessment template (OPCRIT+). METHODS: First, three consultant psychiatrists using a modified version of the Physician Documentation Quality Instrument-9 (PDQI-9) blindly rated fifty MSEs written using OPCRIT+ and fifty normal MSEs written with no template. Second, we conducted an audit to compare the frequency with which individual components of the MSE were documented in the normal MSEs compared with the OPCRIT+MSEs. RESULTS: PDQI-9 ratings indicated that the OPCRIT+MSEs were more 'Thorough', 'Organized', 'Useful' and 'Comprehensible' as well as being of an overall higher quality than the normal MSEs. The audit identified that the normal MSEs contained fewer mentions of the individual components of 'Thought content', 'Anxiety' and 'Cognition & Insight'. CONCLUSIONS: These results indicate that a semi-structured assessment template significantly improves the quality of MSE recording by junior doctors within EHRs. Future work should focus on whether such improvements translate into better patient outcomes and have the ability to improve the quality of information available on EHRs to researchers.

Harnessing clinical psychiatric data with an electronic assessment tool (OPCRIT+): the utility of symptom dimensions.

Progress in personalised psychiatry is dependent on researchers having access to systematic and accurately acquired symptom data across clinical diagnoses. We have developed a structured psychiatric assessment tool, OPCRIT+, that is being introduced into the electronic medical records system of the South London and Maudsley NHS Foundation Trust which can help to achieve this. In this report we examine the utility of the symptom data being collected with the tool. Cross-sectional mental state data from a mixed-diagnostic cohort of 876 inpatients was subjected to a principal components analysis (PCA). Six components, explaining 46% of the variance in recorded symptoms, were extracted. The components represented dimensions of mania, depression, positive symptoms, anxiety, negative symptoms and disorganization. As indicated by component scores, different clinical diagnoses demonstrated distinct symptom profiles characterized by wide-ranging levels of severity. When comparing the predictive value of symptoms against diagnosis for a variety of clinical outcome measures (e.g. 'Overactive, aggressive behaviour'), symptoms proved superior in five instances (R(2) range: 0.06-0.28) whereas diagnosis was best just once (R(2):0.25). This report demonstrates that symptom data being routinely gathered in an NHS trust, when documented on the appropriate tool, have considerable potential for onward use in a variety of clinical and research applications via representation as dimensions of psychopathology.