Supporting integration: the creation of a framework to support the design and delivery of clinical academic integration across a complex system.

Transforming outcomes for patients by aligning and integrating care requires complex systems change and management across multiple organisational boundaries. This case study outlines one part of the integration journey across a partnership between three independent NHS foundation trusts with strong affiliations to two universities, the combined expertise of which places them at the forefront of being able to deliver the best heart and lung outcomes for patients. It specifically describes the process of designing, testing and implementing a bespoke tool called the Clinical Academic Integration Framework (CAIF) to support clinical and academic teams in owning, planning and delivering their paths to full integration, defined as 'one team, across multiple sites' in this context.

How helpful are Patient and Public Involvement strategic documents - Results of a framework analysis using 4Pi National Involvement Standards.

Background: Patient and Public Involvement (PPI) strategic documents are viewed as an essential feature of organisational commitment to openness and transparency. They provide a mechanism to communicate opportunities for wider community influence in healthcare. The absence of documentation can be negatively interpreted, for example during regulatory inspection, as a lack of intent by organisations to collaborate with a broad constituency.

The role of patients and carers in diffusing a health-care innovation: A case study of "My Medication Passport".

Background: Patients are increasingly recognized as playing important roles in improving health services. Little is known about the mechanisms by which patients develop and diffuse local innovations in a complex health-care system.

Objective: To ascertain how diffusion of an innovation, My Medication Passport, occurred and roles played by patients in it.

Differential effects of Foxp2 disruption in distinct motor circuits.

Disruptions of the FOXP2 gene cause a speech and language disorder involving difficulties in sequencing orofacial movements. FOXP2 is expressed in cortico-striatal and cortico-cerebellar circuits important for fine motor skills, and affected individuals show abnormalities in these brain regions. We selectively disrupted Foxp2 in the cerebellar Purkinje cells, striatum or cortex of mice and assessed the effects on skilled motor behaviour using an operant lever-pressing task.

Professionals learning together with patients: An exploratory study of a collaborative learning Fellowship programme for healthcare improvement.

Improving the quality of healthcare involves collaboration between many different stakeholders. Collaborative learning theory suggests that teaching different professional groups alongside each other may enable them to develop skills in how to collaborate effectively, but there is little literature on how this works in practice. Further, though it is recognised that patients play a fundamental role in quality improvement, there are few examples of where they learn together with professionals.

Foxp transcription factors suppress a non-pulmonary gene expression program to permit proper lung development.

The inhibitory mechanisms that prevent gene expression programs from one tissue to be expressed in another are poorly understood. Foxp1/2/4 are forkhead transcription factors that repress gene expression and are individually important for endoderm development. We show that combined loss of all three Foxp1/2/4 family members in the developing anterior foregut endoderm leads to a loss of lung endoderm lineage commitment and subsequent development.

The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice.

Aims/hypothesis: Several forkhead box (FOX) transcription factor family members have important roles in controlling pancreatic cell fates and maintaining beta cell mass and function, including FOXA1, FOXA2 and FOXM1. In this study we have examined the importance of FOXP1, FOXP2 and FOXP4 of the FOXP subfamily in islet cell development and function.

Methods: Mice harbouring floxed alleles for Foxp1, Foxp2 and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenic mice to generate single and compound Foxp mutant mice.

Foxp1/2/4 regulate endochondral ossification as a suppresser complex.

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification.

Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected.

The international spread of Academic Health Science Centres: a scoping review and the case of policy transfer to England.

Academic Health Science Centres (AHSCs) have been a key feature of the North American healthcare landscape for many years, and the term is becoming more widely used internationally. The defining feature of these complex organisations is a tripartite mission of delivering high quality research, medical education and clinical care. The biomedical innovations developed in AHSCs are often well documented, but less is known about the policy and organisational processes which enable the translation of research into patient care.

What can mice tell us about Foxp2 function?

Disruptions of the FOXP2 gene cause a rare speech and language disorder, a discovery that has opened up novel avenues for investigating the relevant neural pathways. FOXP2 shows remarkably high conservation of sequence and neural expression in diverse vertebrates, suggesting that studies in other species are useful in elucidating its functions. Here we describe how investigations of mice that carry disruptions of Foxp2 provide insights at multiple levels: molecules, cells, circuits and behaviour.

Moving improvement research closer to practice: the Researcher-in-Residence model.

The traditional separation of the producers of research evidence in academia from the users of that evidence in healthcare organisations has not succeeded in closing the gap between what is known about the organisation and delivery of health services and what is actually done in practice. As a consequence, there is growing interest in alternative models of knowledge creation and mobilisation, ones which emphasise collaboration, active participation of all stakeholders, and a commitment to shared learning. Such models have robust historical, philosophical and methodological foundations but have not yet been embraced by many of the people working in the health sector.

Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.

The most well-described example of an inherited speech and language disorder is that observed in the multigenerational KE family, caused by a heterozygous missense mutation in the FOXP2 gene. Affected individuals are characterized by deficits in the learning and production of complex orofacial motor sequences underlying fluent speech and display impaired linguistic processing for both spoken and written language. The FOXP2 transcription factor is highly similar in many vertebrate species, with conserved expression in neural circuits related to sensorimotor integration and motor learning.

Generation of mice with a conditional Foxp2 null allele.

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12-14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain.

The importance of planning for the future.

This article explains various mechanisms that are available to plan for the future prior to the development of incapacity. These include powers of attorney, revocable living trusts, advance medical directives such as powers of attorney for health care and living wills, psychiatric advance directives and guardianships and conservatorships. Case examples are utilized to illustrate the consequences of a failure to plan and what can be accomplished through advance planning.

Identification of functional domains in the RAD51L2 (RAD51C) protein and its requirement for gene conversion.

The RAD51 protein plays a key part in the process of homologous recombination through its catalysis of homologous DNA pairing and strand exchange. Additionally five novel mammalian RAD51-like proteins have been identified in mammalian cells, but their roles in homologous recombination are much less well established. These RAD51-like proteins form two different complexes, but only the RAD51L2 (RAD51C) protein is a part of both complexes.

Role of mammalian RAD51L2 (RAD51C) in recombination and genetic stability.

The highly conserved RAD51 protein has a central role in homologous recombination. Five novel RAD51-like genes have been identified in mammalian cells, but little is known about their functions. A DNA damage-sensitive hamster cell line, irs3, was found to have a mutation in the RAD51L2 gene and an undetectable level of RAD51L2 protein.