Motivational and metacognitive feedback in an ITS: linking past states and experiences to current problems

Feedback is an important element in learning as it can provide learners with both information about progress as well as external motivational stimuli, providing them with an opportunity for reflection. Motivation and metacognition are strongly intertwined, with learners high in self-efficacy more likely to use a variety of self-regulatory learning strategies, as well as to persist longer on challenging tasks. Learning from past experience involves metacognitive processes as an act of reflecting upon one’s own experience and, coupled with existing knowledge, aids the acquisition and construction of further knowledge. The aim of the research was to improve the learner’s focus on the process and experience of problem solving while using an Intelligent Tutoring System (ITS), by addressing the primary question: what are the effects of including motivational and metacognitive feedback based on the learner’s past states and experiences? An existing ITS, SQL-Tutor, was used in a study with participants from first year undergraduate degrees studying a database module. The study used two versions of SQL-Tutor: the Control group used a base version providing domain feedback and the Study group used an extended version that also provided motivational and metacognitive feedback. Three sources of data collection were used: module summative assessments, ITS log files and a post-study questionnaire. The analysis included both pre-post comparisons and how the participants interacted with the system, for example their persistence in problem-solving and the degree to which they referred to past learning. Comparisons between groups showed some differing trends both in learning and behaviour in favour of the Study group, though these trends were not significantly different. The study findings showed promise for the use of motivational and metacognitive feedback based on the learners’ past states and experiences that could be used as a basis for future research work and refinement

Influence and change: a study of the ethical decision making of trainee accountants

This thesis is concerned with the subject of ethical decision making. A large number of theoretical models of ethical decision making have been developed in recent years. Apart from a small number of studies, there has been very little empirical testing of the theoretical frameworks. Even fewer studies have examined ethical decision making in a longitudinal framework. This thesis defines and extends a part of one of the models, and tests it longitudinally. The longitudinal context allows dynamic issues in ethical decision making to be explored - how ethical decision making changes over time in response to various individual and situational factors. An important debate in the ethical decision making literature concerns the appropriate conceptual basis for ethical judgement. Most previous studies have focused either on the Cognitive Moral Development construct from psychology or on moral philosophy as the root of ethical judgement. This study develops existing theory to accommodate a third basis, that of personal values. The results of the study show that the personal values construct has significant explanatory power. Further, they suggest that it offers an attractive avenue by which researchers can further explore the relationships between the individual and the organisation. The accountancy profession provides the specific context for this study. Very little is known about how trainee accountants develop a sense of professional ethics. The objective of this study is to examine if and how the ethical decision-making of chartered accountants changes from the time they first join the profession to the end of the three year training period. Previous research has suggested that there may be a possible deficiency in the ethical development of accountants, and that accountancy training may not equip trainees to deal with the ethical conflicts which can arise in their work. Specifically, there is a critical view in the UK accounting literature that professional ethics training tends to focus on rule-following, and does not develop trainees' analytical ethical reasoning abilities. One of the aims of this study is, therefore, to assess the impact of existing professional training programmes as one of a number of individual and situational factors which may influence the ethical judgement of trainee chartered accountants. In order to do this, one group of trainees, a subset of the graduates who joined professional accountancy firms in autumn 1994, were surveyed at different points during their three-year Training Contracts. The study is unique in terms of its context, a large scale survey of UK trainee chartered accountants, and in terms of its longitudinal methodology. The results illustrate the possibility that different standards or sets of values e. g. personal and professional, can be brought to bear on single decisions in the professional context. Further, the experience of professional training and socialisation does not appear to aid trainees in resolving this type of conflict. In this study, personal values are found to be a major influence on ethical judgement across scenarios and across time while organisational values become increasingly important over time. In particular, the results suggest that commercial organisational values affect trainees themselves, not just their decision making, by influencing their personal values over time. Change in trainees' personal values, and correspondingly on their ethical judgement, does not appear to be brought about by specific job-related variables such as ethics training, peer group opinion or external pressures of time. It seems more likely that these specific factors are absorbed by trainees as subconscious indicators of an organisation's values. It makes sense then that the study also shows that the impact of these organisational values on personal values is moderated by organisational commitment, the willingness to believe in an organisation's goals and values

Influence and change: a study of the ethical decision making of trainee accountants

This thesis is concerned with the subject of ethical decision making. A large number of theoretical models of ethical decision making have been developed in recent years. Apart from a small number of studies, there has been very little empirical testing of the theoretical frameworks. Even fewer studies have examined ethical decision making in a longitudinal framework. This thesis defines and extends a part of one of the models, and tests it longitudinally. The longitudinal context allows dynamic issues in ethical decision making to be explored - how ethical decision making changes over time in response to various individual and situational factors. An important debate in the ethical decision making literature concerns the appropriate conceptual basis for ethical judgement. Most previous studies have focused either on the Cognitive Moral Development construct from psychology or on moral philosophy as the root of ethical judgement. This study develops existing theory to accommodate a third basis, that of personal values. The results of the study show that the personal values construct has significant explanatory power. Further, they suggest that it offers an attractive avenue by which researchers can further explore the relationships between the individual and the organisation. The accountancy profession provides the specific context for this study. Very little is known about how trainee accountants develop a sense of professional ethics. The objective of this study is to examine if and how the ethical decision-making of chartered accountants changes from the time they first join the profession to the end of the three year training period. Previous research has suggested that there may be a possible deficiency in the ethical development of accountants, and that accountancy training may not equip trainees to deal with the ethical conflicts which can arise in their work. Specifically, there is a critical view in the UK accounting literature that professional ethics training tends to focus on rule-following, and does not develop trainees' analytical ethical reasoning abilities. One of the aims of this study is, therefore, to assess the impact of existing professional training programmes as one of a number of individual and situational factors which may influence the ethical judgement of trainee chartered accountants. In order to do this, one group of trainees, a subset of the graduates who joined professional accountancy firms in autumn 1994, were surveyed at different points during their three-year Training Contracts. The study is unique in terms of its context, a large scale survey of UK trainee chartered accountants, and in terms of its longitudinal methodology. The results illustrate the possibility that different standards or sets of values e. g. personal and professional, can be brought to bear on single decisions in the professional context. Further, the experience of professional training and socialisation does not appear to aid trainees in resolving this type of conflict. In this study, personal values are found to be a major influence on ethical judgement across scenarios and across time while organisational values become increasingly important over time. In particular, the results suggest that commercial organisational values affect trainees themselves, not just their decision making, by influencing their personal values over time. Change in trainees' personal values, and correspondingly on their ethical judgement, does not appear to be brought about by specific job-related variables such as ethics training, peer group opinion or external pressures of time. It seems more likely that these specific factors are absorbed by trainees as subconscious indicators of an organisation's values. It makes sense then that the study also shows that the impact of these organisational values on personal values is moderated by organisational commitment, the willingness to believe in an organisation's goals and values

The impact of hypoxia on the host-pathogen interaction between neutrophils and staphylococcus aureus

Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with Staphylococcus aureus a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of S. aureus, including the production of virulence factors. Hypoxia thereby shapes the host–pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host–pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to S. aureus and may uncover novel therapeutic targets and strategies

Vaccination with live attenuated simian immunodeficiency virus for 21 days protects against superinfection

AbstractThe identification of mechanisms that prevent infection with human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) would facilitate the development of an effective AIDS vaccine. In time-course experiments, protection against detectable superinfection with homologous wild-type SIV was achieved within 21 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral immunity. Partial protection against superinfection was achieved within 10 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral and cellular immunity. Furthermore, co-inoculation of live attenuated SIV with wild-type SIV resulted in a significant reduction in peak virus loads compared to controls that received wild-type SIV alone. These findings imply that innate immunity or non-immune mechanisms are a significant component of early protection against superinfection conferred by inoculation with live attenuated SIV

Therapeutic potential of regulatory T cells in preeclampsia-opportunities and challenges

Inflammation is a central feature and is implicated as a causal factor in preeclampsia and other hypertensive disorders of pregnancy. Inflammatory mediators and leukocytes, which are elevated in peripheral blood and gestational tissues, contribute to the uterine vascular anomalies and compromised placental function that characterize particularly the severe, early onset form of disease. Regulatory T (Treg) cells are central mediators of pregnancy tolerance and direct other immune cells to counteract inflammation and promote robust placentation. Treg cells are commonly perturbed in preeclampsia, and there is evidence Treg cell insufficiency predates onset of symptoms. A causal role is implied by mouse studies showing sufficient numbers of functionally competent Treg cells must be present in the uterus from conception, to support maternal vascular adaptation and prevent later placental inflammatory pathology. Treg cells may therefore provide a tractable target for both preventative strategies and treatment interventions in preeclampsia. Steps to boost Treg cell activity require investigation and could be incorporated into pregnancy planning and preconception care. Pharmacological interventions developed to target Treg cells in autoimmune conditions warrant consideration for evaluation, utilizing rigorous clinical trial methodology, and ensuring safety is paramount. Emerging cell therapy tools involving in vitro Treg cell generation and/or expansion may in time become relevant. The success of preventative and therapeutic approaches will depend on resolving several challenges including developing informative diagnostic tests for Treg cell activity applicable before conception or during early pregnancy, selection of relevant patient subgroups, and identification of appropriate windows of gestation for intervention.Sarah A. Robertson, Ella S. Green, Alison S. Care, Lachlan M. Moldenhauer, Jelmer R. Prins, M. Louise Hull, Simon C. Barry and Gustaaf Dekker

A posture and mobility training package for care home staff: results of a cluster randomised controlled feasibility trial (the PATCH trial)

Background: provision of care for care home residents with complex needs is challenging. Physiotherapy and activity interventions can improve well-being but are often time-limited and resource intensive. A sustainable approach is to enhance the confidence and skills of staff who provide care. This trial assessed the feasibility of undertaking a definitive evaluation of a posture and mobility training programme for care staff. Design and setting: a cluster randomised controlled feasibility trial with embedded process evaluation. Ten care homes in Yorkshire, United Kingdom, were randomised (1:1) to the skilful care training package (SCTP) or usual care (UC). Participants: residents who were not independently mobile. Intervention: SCTP—delivered by physiotherapists to care staff. Objectives and measurements: key objectives informed progression to a definitive trial. Recruitment, retention and intervention uptake were monitored. Data, collected by a blinded researcher, included pain, posture, mobility, hospitalisations and falls. This informed data collection feasibility and participant safety. Results: a total of 348 residents were screened; 146 were registered (71 UC, 75 SCTP). Forty two were lost by 6 months, largely due to deaths. While data collection from proxy informants was good (>95% expected data), attrition meant that data completion rates did not meet target. Data collection from residents was poor due to high levels of dementia. Intervention uptake was variable—staff attendance at all sessions ranged from 12.5 to 65.8%. There were no safety concerns. Conclusion: care home and resident recruitment are feasible, but refinement of data collection approaches and intervention delivery are needed for this trial and care home research more widely

Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa

Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19:a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

This study was funded by an investigator-initiated research grant from Insmed (Bridgewater, NJ, USA). The authors acknowledge the funding and logistical support from the UK National Institute for Health and Care Research.Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19.Publisher PDFPeer reviewe