Bacterial artificial chromosomes (BACs) are excellent tools for manipulating large DNA fragments and, as a result, are increasingly utilized to engineer transgenic mice by pronuclear injection. The demand for BAC transgenic mice underscores the need for careful inspection of BAC integrity and fidelity following transgenesis, which may be crucial for interpreting transgene function. Thus, it is imperative that reliable methods for assessing these parameters are available. However, there are limited data regarding whether BAC transgenes routinely integrate in the mouse genome as intact molecules, how BAC transgenes behave as they are passed through the germline across successive generations, and how variation in BAC transgene copy number relates to transgene expression. To address these questions, we used Taqman real-time PCR to estimate BAC transgene copy number in BAC transgenic embryos and lines. Here we demonstrate the reproducibility of copy number quantification with this method, and describe the variation in copy number across independent transgenic lines. In addition, polymorphic marker analysis suggests the majority of BAC transgenic lines contain intact molecules. Notably, all lines containing multiple BAC copies also contain all BAC-specific markers. Three of 23 founders analyzed contained BAC transgenes integrated into more than one genomic location. Finally, we show increased BAC transgene copy number correlates with increased BAC transgene expression. In sum, our efforts have provided a reliable method for assaying BAC transgene integrity and fidelity, and data that should be useful for researchers using BACs as transgenic vectors.
Background There is a recognised need to develop clear service models and pathways to provide high quality care in the community for people with complex emotional needs, who may have been given a “personality disorder” diagnosis. Services should be informed by the views of people with these experiences. Aims To identify and synthesise qualitative studies on service user experiences of community mental health care for Complex Emotional Needs. Methods We searched six bibliographic databases for papers published since 2003. We included peer reviewed studies reporting data on service user experiences and views about good care from community-based mental health services for adults with CEN, including generic mental health services and specialist “personality disorder” services. Studies using any qualitative method were included and thematic synthesis used to identify over-arching themes. Results Forty-seven papers were included. Main themes were: 1) The need for a long-term perspective on treatment journeys; 2) The need for individualised and holistic care; 3) Large variations in accessibility and quality of mental health services; 4) The centrality of therapeutic relationships; 5) Impacts of ‘personality disorder’ diagnosis. Themes tended to recur across studies from different countries and years. Discussion Recurrent major themes included wanting support that is individualised and holistic, provides continuity over long journeys towards recovery, and that is delivered by empathetic and well-informed clinicians who are hopeful but realistic about the prospects of treatment. Care that met these simple and clearly stated priorities tended to be restricted to often limited periods of treatment by specialist “personality disorder” services: generic and primary care services were often reported as far from adequate. There is an urgent need to co-design and test strategies for improving long-term support and treatment care for people with “personality disorders” throughout the mental health care system.
Introduction The need to improve the quality of community mental health services for people with Complex Emotional Needs (CEN) is recognised internationally and has become a renewed policy priority in England. Such improvement requires positive engagement from clinicians across the service system, and their perspectives on achieving good practice need to be understood. Aim To synthesise qualitative evidence on clinician perspectives on what constitutes good practice, and what helps or prevents it being achieved, in community mental health services for people with CEN. Methods Six bibliographic databases were searched for studies published since 2003 and supplementary citation tracking was conducted. Studies that used any recognised qualitative method and reported clinician experiences and perspectives on community-based mental health services for adults with CEN were eligible for this review, including generic and specialist settings. Meta-synthesis was used to generate and synthesise over-arching themes across included studies. Results Twenty-nine papers were eligible for inclusion. Six over-arching themes were identified: 1. The use and misuse of diagnosis; 2. The patient journey into services: nowhere to go; 3. Therapeutic relationships: connection and distance; 4. The nature of treatment: not doing too much or too little; 5. Managing safety issues and crises: being measured and proactive; 6. Clinician and wider service needs: whose needs are they anyway? The overall quality of the evidence was moderate. Discussion Through summarising the literature on clinician perspectives on good practice for people with CEN, over-arching priorities were identified on which there appears to be substantial consensus. In their focus on needs such as for a long-term perspective on treatment journeys, high quality and consistent therapeutic relationships, and a balanced approach to safety, clinician priorities are mainly congruent with those found in studies on service user views. They also identify clinician needs that should be met for good care to be provided, including for supervision, joint working and organisational support.
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