Evaluating the articulation of programme theory in practice as observed in Quality Improvement initiatives

Background: The Action-Effect Method(AEM) was co-developed by NIHR CLAHRC Northwest London (CLAHRC NWL) researchers and QI practitioners, building on Driver Diagrams(DD). This study aimed to determine AEM effectiveness in terms of technical aspects (how diagrams produced in practice compared with theoretical ideals) and social aspects (how engagement with the method related to social benefits). Methods Diagrams were scored on criteria developed on theoretical ideals of programme theory. 65 programme theory diagrams were reviewed (21 published Driver Diagrams (External DDs), 22 CLAHRC NWL Driver Diagrams (Internal DDs), and 21 CLAHRC NWL Action-Effect Diagrams(AEDs)). Social functions were studied through ethnographic observation of frontline QI teams in AEM sessions facilitated by QI experts. Qualitative analysis used inductive and deductive coding. Results ANOVA indicated the AEM significantly improved the quality of programme theory diagrams over Internal and External DDs on an average of 5 criteria from an 8-point assessment. Articulated aims were more likely to be patient-focused and high-level in AEDs than DDs. The cause/effect relationships from intervention to overall aim also tended to be clearer and were more likely than DDs to contain appropriate measure concepts. Using the AEM also served several social functions such as facilitating dialogue among multidisciplinary teams, and encouraging teams to act scientifically and pragmatically about planning and measuring QI interventions. Implications: The Action-Effect Method developed by CLAHRC NWL resulted in improvements over Driver Diagrams in articulating programme theory, which has wide-ranging benefits to quality improvement, including encouraging broad multi-disciplinary buy-in to clear aims and pre-planning a rigorous evaluation strategy

Criteria for evaluating programme theory diagrams in quality improvement initiatives: a structured method for appraisal

Background: Despite criticisms that many Quality Improvement (QI) initiatives fail due to incomplete programme theory, there is no defined way to evaluate how programme theory has been articulated. The objective of this research was to develop, and assess the usability and reliability of, scoring criteria to evaluate programme theory diagrams. Methods: Criteria development was informed by published literature and QI experts. Inter-rater reliability was tested between two evaluators. 63 programme theory diagrams (42 driver diagrams and 21 action effect diagrams) were reviewed to establish whether the criteria could support comparative analysis of different approaches to constructing diagrams. Results: Components of the scoring criteria include: assessment of overall aim, logical overview, clarity of components, cause/effect relationships, evidence, and measurement. Independent reviewers had 78% inter-rater reliability. Scoring enabled direct comparison of different approaches to developing programme theory; Action-Effect diagrams were found to have had a statistically significant but moderate improvement in programme theory quality over Driver Diagrams; no significant differences were observed based on the setting in which Driver Diagrams were developed. Conclusions: The scoring criteria summarise the necessary components of programme theory that are thought to contribute to successful QI projects. The viability of the scoring criteria for practical application was demonstrated. Future uses include assessment of individual programme theory diagrams, and comparison of different approaches (e.g. methodological, teaching or other QI support) to produce programme theory. The criteria can be used as a tool to guide the production of better programme theory diagrams, and also highlights where additional support for QI teams could be needed

Tumours in 177 pet hamsters

Background: Even though tumours are considered to occur frequently in pet hamsters, there is only a small number of scientific reports in current literature. Methods: Pathological reports from 177 hamsters were evaluated. Results: Of these, 78 were male and 75 were female. Median age of affected hamsters was 12 months (range 2–34). Integumental tumours were the most common neoplasms (62%, 109/177). As far as species was known, the number of Syrian hamsters (52%, 30/58) affected by tumours seemed to be lower than the number of affected dwarf hamsters (85%, 47/55). Tumours of the hematopoietic system were the second most frequently neoplasms (17%, 30/177). Relative number of neoplasms of the endocrine system, tumours of the digestive system (1.7%, 3/177) and other tumours (4%, 7/177 each) was low. The majority of integumental tumours were epithelial (66%; 91/126). Conclusion: This study aimed to analyze data from veterinary surgeries and pathological institutes about the occurrence of spontaneous tumours in Syrian hamsters and dwarf hamsters to give information about the frequency of tumours, prognosis and survival time. This is the first study about tumours in pet hamsters in Germany so far

Neocortical hyperexcitability in a genetic model of absence seizures and its reduction by levetiracetam

PURPOSE: To study the effect of the antiepileptic drug levetiracetam (LEV) on the patterns of intrinsic optical signals (IOSs) generated by slices of the somatosensory cortex obtained from 3- and 6-month-old WAG/Rij and age-matched, nonepileptic control (NEC) rats. METHODS: WAG/Rij and NEC animals were anesthetized with enfluorane and decapitated. Brains were quickly removed, and neocortical slices were cut coronally with a vibratome, transferred to a submerged tissue chamber, and superfused with oxygenated artificial cerebrospinal fluid (aCSF). Slices were illuminated with a dark-field condensor and examined with a x2.5 objective; images were processed with a real time digital video image-enhancement system. Images were acquired before (background) and during electrical stimulation with a temporal resolution of 10 images/s and were displayed in pseudocolors. Extracellular stimuli (200 micros; <4 V) were delivered through bipolar stainless steel electrodes placed in the white matter. RESULTS: IOSs recorded in NEC slices bathed in control aCSF became less intense and of reduced size with age (p < 0.05); this trend was not seen in WAG/Rij slices. Age-dependent decreases in IOS intensity and area size were also seen in NEC slices superfused with aCSF containing the convulsant 4-aminopyridine (4-AP, 5 microM); in contrast, significant increases in both parameters occurred with age in 4-AP-treated WAG/Rij slices (p < 0.05). Under any of these conditions, the IOS intensity and area size slices were larger in WAG/Rij than in NEC slices. LEV (50-500 microM) application to WAG/Rij slices caused dose-dependent IOS reductions that were evident both in control and in 4-AP-containing aCSF and were more pronounced in 6-month-old tissue. CONCLUSIONS: These data demonstrate age-dependent IOS modifications in NEC and WAG/Rij rat slices and identify a clear pattern of hyperexcitability that occurs in 6-month-old WAG/Rij neocortical tissue, an age when absence seizures occur in all animals. The ability of LEV to reduce these patterns of network hyperexcitability supports the potential use of this new antiepileptic drug in primary generalized epileptic disorders

Potentiality in Aristotle's psychology and ethics

The distinction between potentiality and actuality in Aristotle has its origin in Platonic ethics. In his psychological and ethical works Aristotle’s notion of potentiality is embedded in a causal framework that is characteristic of life in general. A key theme is the distinction of various meanings of ‘to know’. In his early work the possession of knowledge is distinguished from its use. In De anima Aristotle adds the potentiality for acquiring knowledge as characteristic of the genus human being. He argues that the stages of actualization of knowledge are instances of a more comprehensive biological and ethical development. Life is the fulfillment of soul as formal, efficient and final cause, with the potentiality of body as material cause. The unity of body and soul is derived from the causal nexus of potentiality and actuality, like a power and the instrument in which it resides. In such cases potentiality is complex and depends on numerous conditions. Failure of full realization may occur when any of the necessary conditions of the development and realization of the fulfillment of human life are lacking, whether in the environment (e.g. climate), the body (illness, drunkenness), or the soul (natural virtue, firm character, attention).Political Philosophy and Ethic

The Role of Industry, Geography and Firm Heterogeneity in Credit Risk Diversification

In theory the potential for credit risk diversification for banks could be substantial. Portfolio diversification is driven broadly by two characteristics: the degree to which systematic risk factors are correlated with each other and the degree of dependence individual firms have to the different types of risk factors. We propose a model for exploring these dimensions of credit risk diversification: across industry sectors and across different countries or regions. We find that full firm-level parameter heterogeneity matters a great deal for capturing differences in simulated credit loss distributions. Imposing homogeneity results in overly skewed and fat-tailed loss distributions. These differences become more pronounced in the presence of systematic risk factor shocks: increased parameter heterogeneity greatly reduces shock sensitivity. Allowing for regional parameter heterogeneity seems to better approximate the loss distributions generated by the fully heterogeneous model than allowing just for industry heterogeneity. The regional model also exhibits less shock sensitivity

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

MIDA boronates are hydrolysed fast and slow by two different mechanisms

MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base mediated and the other neutral. The former can proceed more than three orders of magnitude faster than the latter, and involves a rate-limiting attack by a hydroxide at a MIDA carbonyl carbon. The alternative 'neutral' hydrolysis does not require an exogenous acid or base and involves rate-limiting B-N bond cleavage by a small water cluster, (H2O)n. The two mechanisms can operate in parallel, and their relative rates are readily quantified by (18)O incorporation. Whether hydrolysis is 'fast' or 'slow' is dictated by the pH, the water activity and the mass-transfer rates between phases. These findings stand to enable, in a rational way, an even more effective and widespread utilization of MIDA boronates in synthesis

Megascopic Quantum Phenomena. A Critical Study of Physical Interpretations

A megascopic revalidation is offered providing responses and resolutions of current inconsistencies and existing contradictions in present-day quantum theory. As the core of this study we present an independent proof of the Goldstone theorem for a quantum field formulation of molecules and solids. Along with phonons two types of new quasiparticles appear: rotons and translons. In full analogy with Lorentz covariance, combining space and time coordinates, a new covariance is necessary, binding together the internal and external degrees of freedom, without explicitly separating the centre-of-mass, which normally applies in both classical and quantum formulations. The generally accepted view regarding the lack of a simple correspondence between the Goldstone modes and broken symmetries, has significant consequences: an ambiguous BCS theory as well as a subsequent Higgs mechanism. The application of the archetype of the classical spontaneous symmetry breaking, i.e. the Mexican hat, as compared to standard quantum relations, i.e. the Jahn-Teller effect, superconductivity or the Higgs mechanism, becomes a disparity. In short, symmetry broken states have a microscopic causal origin, but transitions between them have a teleological component. The different treatments of the problem of the centre of gravity in quantum mechanics and in field theories imply a second type of Bohr complementarity on the many-body level opening the door for megascopic representations of all basic microscopic quantum axioms with further readings for teleonomic megascopic quantum phenomena, which have no microscopic rationale: isomeric transitions, Jahn-Teller effect, chemical reactions, Einstein-de Haas effect, superconductivity-superfluidity, and brittle fracture.Comment: 117 pages, 17 sections, final revised version from 20 May 2019 but uploaded after the DOI was know