Understanding and responding when things go wrong: key principles for primary care educators

Learning from events with unwanted outcomes is an important part of workplace based education and providing evidence for medical appraisal and revalidation. It has been suggested that adopting a ‘systems approach’ could enhance learning and effective change. We believe the following key principles should be understood by all healthcare staff, especially those with a role in developing and delivering educational content for safety and improvement in primary care. When things go wrong, professional accountability involves accepting there has been a problem, apologising if necessary and committing to learn and change. This is easier in a ‘Just Culture’ where wilful disregard of safe practice is not tolerated but where decisions commensurate with training and experience do not result in blame and punishment. People usually attempt to achieve successful outcomes, but when things go wrong the contribution of hindsight and attribution bias as well as a lack of understanding of conditions and available information (local rationality) can lead to inappropriately blame ‘human error’. System complexity makes reduction into component parts difficult; thus attempting to ‘find-and-fix’ malfunctioning components may not always be a valid approach. Finally, performance variability by staff is often needed to meet demands or cope with resource constraints. We believe understanding these core principles is a necessary precursor to adopting a ‘systems approach’ that can increase learning and reduce the damaging effects on morale when ‘human error’ is blamed. This may result in ‘human error’ becoming the starting point of an investigation and not the endpoint

Triple Threat: My Journey as a Black Lesbian Athlete in Search of Additional Black Lesbian Student-Athletes

Black lesbian women experience a triple threat based on three components of their identity – race, gender, and sexual orientation – places them on the lower ranks of the totem pole of U.S. social hierarchy. With this in mind, the purpose of this study was to explore how Black lesbian student-athletes negotiate three components of their identity – race, sexual orientation, and being a female NCAA Division I student-athlete – through semi-structured interviews in order to provide these student-athletes with a mechanism to have a voice and express their individual experiences. Since I experienced difficulty in obtaining participants that met the criteria, I have included myself as a co-participant in order to tell my journey of researching a population I identify with – one who has been forced to the margins of society along with the black community

Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

Observation of Amounts of Movement Practice Provided during Stroke Rehabilitation

Objective To investigate how much movement practice occurred during stroke rehabilitation, and what factors might influence doses of practice provided. Design Observational survey of stroke therapy sessions. Setting Seven inpatient and outpatient rehabilitation sites. Participants We observed a convenience sample of 312 physical and occupational therapy sessions for people with stroke. Interventions Not applicable. Main Outcome Measures We recorded numbers of repetitions in specific movement categories and data on potential modifying factors (patient age, side affected, time since stroke, FIM item scores, years of therapist experience). Descriptive statistics were used to characterize amounts of practice. Correlation and regression analyses were used to determine whether potential factors were related to the amount of practice in the 2 important categories of upper extremity functional movements and gait steps. Results Practice of task-specific, functional upper extremity movements occurred in 51% of the sessions that addressed upper limb rehabilitation, and the average number of repetitions/session was 32 (95% confidence interval [CI]=20–44). Practice of gait occurred in 84% of sessions that addressed lower limb rehabilitation and the average number of gait steps/session was 357 (95% CI=296–418). None of the potential factors listed accounted for significant variance in the amount of practice in either of these 2 categories. Conclusions The amount of practice provided during poststroke rehabilitation is small compared with animal models. It is possible that current doses of task-specific practice during rehabilitation are not adequate to drive the neural reorganization needed to promote function poststroke optimally

A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are closely related orphan nuclear hormone receptors that play a critical role as xenobiotic sensors in mammals. Both receptors regulate the expression of genes involved in the biotransformation of chemicals in a ligand-dependent manner. As the ligand specificity of PXR and CAR have diverged between species, the prediction of in vivo PXR and CAR interactions with a drug are difficult to extrapolate from animals to humans. We report the development of what we believe are novel PXR- and CAR-humanized mice, generated using a knockin strategy, and Pxr- and Car-KO mice as well as a panel of mice including all possible combinations of these genetic alterations. The expression of human CAR and PXR was in the predicted tissues at physiological levels, and splice variants of both human receptors were expressed. The panel of mice will allow the dissection of the crosstalk between PXR and CAR in the response to different drugs. To demonstrate the utility of this panel of mice, we used the mice to show that the in vivo induction of Cyp3a11 and Cyp2b10 by phenobarbital was only mediated by CAR, although this compound is described as a PXR and CAR activator in vitro. This panel of mouse models is a useful tool to evaluate the roles of CAR and PXR in drug bioavailability, toxicity, and efficacy in humans

Messages in Paint: An archaeometric analysis of pigment use in Aboriginal Australia focusing on the production of rock art

Anthropogenically modified pigments are held to be some of the earliest, most unambiguous and persistent evidence for behavioural modernity, frequently (and often tenuously) invoked as material expression of symbolic thought and action. Recent finds, increases in the sophistication of analytic techniques and theoretical frameworks have renewed interest in ochre, reflected by a spike in actualistic studies, investigations of pigment morphology and geochemistry. Archaeological studies continue a bias towards Pleistocene pigments, while archaeometric research continues to focus on ochre from known source locations, and in Australia, ethnographically documented mines. Here I take a different tack, targeting Holocene ochres, focusing on pigments with at least one known, indisputably symbolic function- the production of rock art. As part of the physical and metaphorical (cultural) landscape, rock art offers a unique pigment archive as it remains in the location in which it was created. A decade since the first published application of portable X-ray Fluorescence (pXRF) to rock art there has been an absence of critical scrutiny and methodological development. Aiming to redress this, I use conventional and Synchrotron X-ray Diffraction, Micro Computed Tomography and Scanning Electron Microscopy to explain and evaluate pXRF. I develop novel methods of using geochemical data to identify paint mineralogy (including differentiating between paints of the same colour), recognise the chemical signatures of taphonomy and compare ochres from excavated contexts with rock art. Interpreting the resultant elemental profiles relies on understanding the complex taphonomy of pigments and the chemical expression of non-cultural phenomena, something not adequately addressed previously. This work therefore offers a non-invasive means by which large scale studies of archaeological pigments can be undertaken

Clinical consequences of a miscalibrated digoxin immunoassay

A routine audit revealed that the analytical method used to measure digoxin concentrations by our statewide pathology provider in 2009 was underestimating digoxin concentrations by 10%. The assay was recalibrated by the manufacturer in 2010, but clinical outcomes of the underestimation were never measured. This is a pilot study to describe the prescribing behavior around out-of-range digoxin concentrations and to assess whether miscalibrated digoxin immunoassays contribute to clinically relevant effects, as measured by inappropriate alterations in digoxin doses.About 30,000 digoxin concentrations across the State Hospital system were obtained in 2 periods before and after recalibration of the digoxin assay. Digoxin concentration means were calculated and compared and were statistically significantly different. Subsequently, a single-centered retrospective review of 50 randomly chosen charts was undertaken to study the clinical implications of the underestimated concentrations.Mean digoxin concentrations for 2009 and 2011 were significantly different by 8.8% (confidence interval, 7.0%-10.6%). After recalculating the 2009 concentrations to their "corrected" values, there was a 16% increase in the number of concentrations within the range when compared with the 2011 concentrations (41.48% versus 48.04%). However, overall, this did not cause unnecessary dose changes in patients who were "borderline" or outside the therapeutic range when compared with controls (P = 0.10). The majority of decisions were based on the clinical impression rather than concentration alone (85.1% versus 14.9%), even when the concentration was outside the "therapeutic range."Although recalculating digoxin concentrations measured during 2009 to their corrected values produced a significant change in concentration and values inside and outside the range, this does not seem to have had an influence on patient treatment. Rather, clinicians tended to use the clinical impression to dose digoxin

The relationship between moral development, distorted cognitions and social problem solving amongst men with intellectual disabilities who have a history of criminal offending

Aim: Little is known about the self-rated health status of people with co-morbid autism and intellectual disabilities (ID) in whole country populations. This paper will present analysis of: self-rated general health status, demographic factors, and prevalence of other disabilities for people with co-morbid autism and ID, as well as people with autism only. Method: We analysed data from Scotland’s Census 2011, and generated descriptive statistics. Results: People with co-morbid autism and ID (n=5,709)comprised 0.1% of the total population of Scotland (n=5,295,403) and 18 .0% of the whole population of people with autism in Scotland(n=31,712) across all ages. Only 2,863 (50.1%) people with co-morbid autism and ID rated their health as good or very good, compared with 19,97 1 (76.8%) of all people with autism only. Conclusions: Health is poorer for people with c o-morbid autism and ID than for people with autism only. Further analysis will explore the impact of individual and household characteristics on the health o f people with co-morbid autism and ID

Effect of room temperature transport vials on DNA quality and phylogenetic composition of faecal microbiota of elderly adults and infants

Background: Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal microbiota is widely used as a non-invasive and ethically simple proxy for intestinal biopsies. There is an urgent need for collection and transport media that would allow faecal sampling at distance from the processing laboratory, obviating the need for same-day DNA extraction recommended by previous studies of freezing and processing methods for stool. We compared the faecal bacterial DNA quality and apparent phylogenetic composition derived using a commercial kit for stool storage and transport (DNA Genotek OMNIgene GUT) with that of freshly extracted samples, 22 from infants and 20 from older adults. Results: Use of the storage vials increased the quality of extracted bacterial DNA by reduction of DNA shearing. When infant and elderly datasets were examined separately, no differences in microbiota composition were observed due to storage. When the two datasets were combined, there was a difference according to a Wilcoxon test in the relative proportions of Faecalibacterium, Sporobacter, Clostridium XVIII, and Clostridium XlVa after 1 week's storage compared to immediately extracted samples. After 2 weeks' storage, Bacteroides abundance was also significantly different, showing an apparent increase from week 1 to week 2. The microbiota composition of infant samples was more affected than that of elderly samples by storage, with significantly higher Spearman distances between paired freshly extracted and stored samples (