From Shop floor to top floor. An exploratory study of sustainable progression in the retial sector: the case of Morrisons

There has been increasing political and media attention given to the issue of social mobility in recent times. The interest has been sparked by research which suggests that social mobility may have stalled or even declined in the UK during the post-war period. Various factors have been identified as inhibiting social mobility including early years experiences in the home and at school, education and health along with area based influences. Employment and labour market experiences are also key factors contributing to social mobility with the importance of ‘getting a job’ and ‘sustainable progression’ increasingly recognised as an important means of improving social mobility. There now appears consensus that occupational mobility and career development is a key factor in overcoming social mobility, and the extent to which organisations develop pathways and support careers is a critical element in pursuing social mobility. This exploratory study has been commissioned by Morrisons to investigate the factors which impact on progression in the workplace and the effect of these on the social mobility of research participants. The study adopts the framework of ‘career development’ as a construct to explore sustainable progression, drawing on the employment and labour market experiences of employees at Morrisons who, having started on the ‘shop floor’ have progressed to senior management levels in the company. The study is based on their ‘life stories’ to identify the key factors associated with a successful career at Morrisons

Knowledge graph prediction of unknown adverse drug reactions and validation in electronic health records

Unknown adverse reactions to drugs available on the market present a significant health risk and limit accurate judgement of the cost/benefit trade-off for medications. Machine learning has the potential to predict unknown adverse reactions from current knowledge. We constructed a knowledge graph containing four types of node: drugs, protein targets, indications and adverse reactions. Using this graph, we developed a machine learning algorithm based on a simple enrichment test and first demonstrated this method performs extremely well at classifying known causes of adverse reactions (AUC 0.92). A cross validation scheme in which 10% of drug-adverse reaction edges were systematically deleted per fold showed that the method correctly predicts 68% of the deleted edges on average. Next, a subset of adverse reactions that could be reliably detected in anonymised electronic health records from South London and Maudsley NHS Foundation Trust were used to validate predictions from the model that are not currently known in public databases. High-confidence predictions were validated in electronic records significantly more frequently than random models, and outperformed standard methods (logistic regression, decision trees and support vector machines). This approach has the potential to improve patient safety by predicting adverse reactions that were not observed during randomised trials

Understanding How Emerging Same-Sex Couples Make Meaning of Minority Stress: A Narrative Approach

Minority stress—in the form of experiences of prejudice and discrimination—can have negative consequences on individuals in same-sex relationships. However, little is known about the ways in which members of same-sex couples make meaning of minority stress, especially in the context of newly formed relationships that may be most vulnerable to minority stressors. The present study draws upon emerging understandings of couple-level minority stress to investigate the ways in which newly formed same-sex couples make meaning of their minority stress experiences jointly as a couple. A narrative analysis was conducted using data from dyadic interviews with 40 same-sex couples who had been together for at least 6 months but less than 3 years. Analyses highlighted six distinct narrative strategies used by couples when making-meaning of their minority stress experiences: “minority stress made couples stronger,” “minority stress contaminates positive experiences,” “minority stress is not a big deal,” “couples resign in the face of minority stress,” “minority stress is worse than expected,” and “couples hope minority stress experiences will get better.” These findings not only provide valuable evidence for couple-level minority stress constructs, but crucially give a nuanced insight into how same-sex couples that are in the early stages of relationship development, make meaning of their minority stress experiences. Findings have important implications for the design and implementation of effective clinical and counseling interventions aimed at reducing negative outcomes among individuals in same-sex relationships, and the potential for relationship dissolution resulting from minority stress experiences

Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells.

We hypothesized that key antiproliferative target genes for the vitamin D receptor (VDR) were repressed by an epigenetic mechanism in prostate cancer cells resulting in apparent hormonal insensitivity. To explore this possibility, we examined nuclear receptor corepressor expression in a panel of nonmalignant and malignant cell lines and primary cultures, and found frequently elevated SMRT corepressor mRNA expression often associated with reduced sensitivity to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)2D3). For example, PC-3 and DU-145 prostate cancer cell lines had 1.8-fold and twofold increases in SMRT mRNA relative to normal PrEC cells (P<0.05). Similarly, 10/15 primary tumour cultures (including three matched to normal cells from the same donors) had elevated SMRT mRNA levels; generally NCoR1 and Alien were not as commonly elevated. Corepressor proteins often have associated histone deacetylases (HDAC) and reflectively the antiproliferative action of 1alpha,25(OH)2D3 can be restored by cotreatment with low doses of HDAC inhibitors such as trichostatin A (TSA, 15 nM) to induce apoptosis in prostate cancer cell lines. To decipher the transcriptional events that lead to these cellular responses, we undertook gene expression studies in PC-3 cells after cotreatment of 1alpha,25(OH)2D3 plus TSA after 6 h. Examination of known VDR target genes and cDNA microarray analyses revealed cotreatment of 1alpha,25(OH)2D3 plus TSA cooperatively upregulated eight (out of 1176) genes, including MAPK-APK2 and GADD45alpha. MRNA and protein time courses and inhibitor studies confirmed these patterns of regulation. Subsequently, we knocked down SMRT levels in PC-3 cells using a small interfering RNA (siRNA) approach and found that GADD45alpha induction by 1alpha,25(OH)2D3 alone became very significantly enhanced. The same distortion of gene responsiveness, with repressed induction of GADD45alpha was found in primary tumour cultures compared and to matched peripheral zone (normal) cultures from the same donor. These data demonstrate that elevated SMRT levels are common in prostate cancer cells, resulting in suppression of target genes associated with antiproliferative action and apparent 1alpha,25(OH)2D3-insensitivity. This can be targeted therapeutically by combination treatments with HDAC inhibitors

Rapid Automatic Motor Encoding of Competing Reach Options.

Mounting neural evidence suggests that, in situations in which there are multiple potential targets for action, the brain prepares, in parallel, competing movements associated with these targets, prior to implementing one of them. Central to this interpretation is the idea that competing viewed targets, prior to selection, are rapidly and automatically transformed into corresponding motor representations. Here, by applying target-specific, gradual visuomotor rotations and dissociating, unbeknownst to participants, the visual direction of potential targets from the direction of the movements required to reach the same targets, we provide direct evidence for this provocative idea. Our results offer strong empirical support for theories suggesting that competing action options are automatically represented in terms of the movements required to attain them. The rapid motor encoding of potential targets may support the fast optimization of motor costs under conditions of target uncertainty and allow the motor system to inform decisions about target selection.Funding from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Wellcome Trust, the Royal Society Noreen Murray Professorship in Neurobiology (to D.M.W.), the Canadian Foundation for Innovation, and the Ontario Innovation Trust supported this study. J.P.G. was supported by an NSERC Banting Postdoctoral Fellowship and a Canadian Institutes of Health Research Postdoctoral Fellowship. B.M.S. was supported by an NSERC graduate scholarship

Using clinical audit to improve the quality of obstetric care at the Tibetan Delek Hospital in North India: a longitudinal study

BACKGROUND: The Tibetan Delek Hospital is a small general hospital providing primary and secondary care for the Tibetan refugee community and the local Indian population in Dharamsala, Himachal Pradesh, North India. In a baseline clinical audit of intrapartum care at the Tibetan Delek Hospital in 1996, high levels of postpartum haemorrhage associated with poor medical management of the third stage of labour, plus inappropriate transfer of women in labour were observed. These audit findings prompted the implementation of changes in the delivery of intrapartum care and follow-up audit cycles to monitor the ongoing effect of these changes. METHODS: The delivery of intrapartum care was modified in two ways. Firstly, nurses, midwives, and doctors were re-trained in the active management of the third stage of labour, which involved the administration of intramuscular syntocinon plus ergometrine with delivery of the anterior shoulder. Secondly partograms were introduced to help rationalise the management of labour, and in particular decisions about when to transfer women in labour. Follow up audits were conducted in 1997, 1998, and 2003 to quantify the effects of these changes. The key measures for improvement included the documented incidence of postpartum haemorrhage and the number of women transferred inappropriately for failure to progress in labour. RESULTS: A sustained reduction of approximately 50% in the incidence of postpartum haemorrhage was observed after the introduction of active management of the third stage of labour. The introduction of the routine use of partograms was associated with a more rational decision-making process regarding transfer during labour. CONCLUSION: Introducing and maintaining a clinical audit cycle can lead to improvements in the quality of obstetric care in a refugee population

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial

Background: Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction (‘optical treatment’) followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching (‘dose’), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. Methods/design: A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. Discussion: This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical modelling of previous trial outcome data. Should the personalized dosing strategy demonstrate superiority over the standardized dosing strategy, then its adoption into routine practice could bring practical benefits in reducing the duration of treatment needed to achieve an optimal outcome