Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM.

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients

A review of hot-melt extrusion: process technology to pharmaceutical products [Review article]

Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems

Intestinal epithelial replacement by transplantation of cultured murine and human cells into the small intestine.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model

Trauma-informed care in the UK:where are we? A qualitative study of health policies and professional perspectives

BACKGROUND: Trauma-informed (TI) approach is a framework for a system change intervention that transforms the organizational culture and practices to address the high prevalence and impact of trauma on patients and healthcare professionals, and prevents re-traumatization in healthcare services. Review of TI approaches in primary and community mental healthcare identified limited evidence for its effectiveness in the UK, however it is endorsed in various policies. This study aimed to investigate the UK-specific context through exploring how TI approaches are represented in health policies, and how they are understood and implemented by policy makers and healthcare professionals. METHODS: A qualitative study comprising of a document analysis of UK health policies followed by semi-structured interviews with key informants with direct experience of developing and implementing TI approaches. We used the Ready Extract Analyse Distil (READ) approach to guide policy document review, and the framework method to analyse data. RESULTS: We analysed 24 documents and interviewed 11 professionals from healthcare organizations and local authorities. TI approach was included in national, regional and local policies, however, there was no UK- or NHS-wide strategy or legislation, nor funding commitment. Although documents and interviews provided differing interpretations of TI care, they were aligned in describing the integration of TI principles at the system level, contextual tailoring to each organization, and addressing varied challenges within health systems. TI care in the UK has had piecemeal implementation, with a nation-wide strategy and leadership visible in Scotland and Wales and more disjointed implementation in England. Professionals wanted enhanced coordination between organizations and regions. We identified factors affecting implementation of TI approaches at the level of organization (leadership, service user involvement, organizational culture, resource allocation, competing priorities) and wider context (government support, funding). Professionals had conflicting views on the future of TI approaches, however all agreed that government backing is essential for implementing policies into practice. CONCLUSIONS: A coordinated, more centralized strategy and provision for TI healthcare, increased funding for evaluation, and education through professional networks about evidence-based TI health systems can contribute towards evidence-informed policies and implementation of TI approaches in the UK. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08461-w

Transverse and longitudinal characterization of electron beams using interaction with optical near-fields

We demonstrate an experimental technique for both transverse and longitudinal characterization of bunched femtosecond free electron beams. The operation principle is based on monitoring of the current of electrons that obtained an energy gain during the interaction with the synchronized optical near-field wave excited by femtosecond laser pulses. The synchronous accelerating/decelerating fields confined to the surface of a silicon nanostructure are characterized using a highly focused sub-relativistic electron beam. Here the transverse spatial resolution of 450 nm and femtosecond temporal resolution achievable by this technique are demonstrated

Permission to exist *

Abstract We provide a new model that generates persistent performance differences amongst seemingly similar enterprises. Our model provides a mechanism whereby efficient incumbent rivals can give permission for an inefficient firm to exist in the presence of efficient entrants. We demonstrate that, in a repeated game, an efficient incumbent has a unilateral incentive to establish a relational contract that softens price competition to either strengthen the inefficient firm in a war of attrition that emerges post-entry or reduce the value to the inefficient firm of selling its position to entrants. The paper provides conditions under which that equilibrium exists and derives a number of empirical predictions as implications of the model. It is demonstrated that performance differences are likely to be associated with stability in the identity of firms in the market