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BackgroundAlthough many people are supportive of their deidentified health care data being used for research, concerns about privacy, safety, and security of health care data remain. There is low awareness about how data are used for research and related governance. Transparency about how health data are used for research is crucial for building public trust. One proposed solution is to ensure that affected communities are notified, particularly marginalized communities where there has previously been a lack of engagement and mistrust. ObjectiveThis study aims to explore patient and public perspectives on the use of deidentified data from electronic health records for musculoskeletal research and to explore ways to build and sustain public trust in health data sharing for a research program (known as “the Data Jigsaw”) piloting new ways of using and analyzing electronic health data. Views and perspectives about how best to engage with local communities informed the development of a public notification campaign about the research. MethodsQualitative methods data were generated from 20 semistructured interviews and 8 focus groups, comprising 48 participants in total with musculoskeletal conditions or symptoms, including 3 carers. A presentation about the use of health data for research and examples from the specific research projects within the program were used to trigger discussion. We worked in partnership with a patient and public involvement group throughout the research and cofacilitated wider community engagement. ResultsRespondents were supportive of their health care data being shared for research purposes, but there was low awareness about how electronic health records are used for research. Security and governance concerns about data sharing were noted, including collaborations with external companies and accessing social care records. Project examples from the Data Jigsaw program were viewed positively after respondents knew more about how their data were being used to improve patient care. A range of different methods to build and sustain trust were deemed necessary by participants. Information was requested about: data management; individuals with access to the data (including any collaboration with external companies); the National Health Service’s national data opt-out; and research outcomes. It was considered important to enable in-person dialogue with affected communities in addition to other forms of information. ConclusionsThe findings have emphasized the need for transparency and awareness about health data sharing for research, and the value of tailoring this to reflect current and local research where residents might feel more invested in the focus of research and the use of local records. Thus, the provision for targeted information within affected communities with accessible messages and community-based dialogue could help to build and sustain public trust. These findings can also be extrapolated to other conditions beyond musculoskeletal conditions, making the findings relevant to a much wider community.

Context: Adult social care need is increasing, posing a challenge to public and societal resources. Musculoskeletal disease and chronic pain are also increasing in prevalence, and given their disabling nature, may be contributing to social care demands. However, we do not know what proportion of adults with chronic musculoskeletal pain use social care services. Objective: To describe social care use in adults with chronic pain. Methods: An online cross-sectional survey was sent to participants of a previous mobile health study investigating people with chronic pain. It collected data on care received in the last month, including providers, frequency and duration of care, demographics and medical diagnoses. Descriptive statistics summarised these data, and a multivariable logistic regression model identified factors associated with care receipt. Findings: There were 981 respondents, 95% identified MSK disease as the cause of their pain. Five hundred twenty-seven (54%) reported receiving social care services in the last month, with the majority (338, 74%) receiving this care informally from family and friends. From multivariate analyses, those receiving care were more likely to have a diagnosis of osteoarthritis or fibromyalgia. Limitations: The sample may not be fully representative of the chronic MSK pain population. Implications: Adults with chronic MSK pain have significant social care use, predominantly informal. Understanding the relationship between MSK diseases and social care may allow better design of social care services in this context, as well as opportunities to develop prevention strategies. Future research should focus on identifying whether these findings are replicated in a more representative sample of people with MSK disease.

Abstract Background Miridesap depletes circulating serum amyloid P (SAP) and dezamizumab (anti-SAP monoclonal antibody) targets SAP on amyloid deposits, triggering amyloid removal. In a phase 1, first-in-human study (FIHS), progressive amyloid removal was observed in some patients after ≤ 3 cycles of miridesap/dezamizumab. Methods This observational, non-interventional study in patients who received miridesap/dezamizumab during the FIHS (planned follow-up: 5 years) evaluated response to treatment based on routine assessments of disease status and key organ function. In a post hoc analysis, patients responding to treatment in the FIHS during follow-up were identified as responders and further categorized as sustained or declining responders. Results In the FIHS, 17/23 patients were treatment responders. Of these patients, seven (immunoglobulin light chain [AL], n = 6; serum amyloid A, n = 1) were considered sustained responders and ten (fibrinogen-a alpha chain [AFib], n = 5; AL, n = 4; apolipoprotein A-I, n = 1) were considered declining responders. We primarily present responder patient-level data for functional, cardiac, laboratory and imaging assessments conducted during the follow-up period, with non-responder data presented as supplementary. Conclusion No further development of miridesap/dezamizumab is planned in amyloidosis. However, long-term follow-up of these patients may provide insight into whether active removal of amyloid deposits has an impact on disease progression. Trial registration ClinicalTrials.gov, NCT01777243. Registered 28 January 2013, https://clinicaltrials.gov/ct2/show/study/NCT01777243 .

Abstract Background In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. Methods Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. Results Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. Conclusions Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).

This paper identifies an alternative perspective on Knowledge Management (KM) in multinational organisations by definition of the concept of Ignorance Management.Furthermore, this paper discusses the dificulties employees face in understanding and comprehending what they need to know to do their jobs, and what implications this can have within global technology intensive environments. The focus is given in particular on multinational organisations where innovation and new knowledge is essential to both shortterm opportunistic value capture and long-term business sustainability. Hence, this paper discusses why managing ignorance is essential for maintaining a strategic knowledge sharing culture within multinational organisations. Furthermore, it develops a novel theory on the nature of knowledge and ignorance while making the distinction between knowns and unknowns as well as between consciousness and ignorance. The theoretical findings have been applied to technology intensive and innovative environments. A case study is explored within the paper, based on findings from one of the largest military contractors in the world, which employs over 100,000 people across the globe. The paper adopts an interpretative philosophy, using the primary strategy of qualitative research. In addition, due to the complexity of the topic, a mixed methods approach has been used for the data collection process. Moreover, participatory action research is undertaken to study individuals’ actions in a particular context and improve organisational strategies and KM practices. The study shows that managing ignorance and adaptiveness in multinational organisations is becoming increasingly important. Thus, the critical question is not just managing what is known but also trying to find ways to manage the unknown. This viewpoint of acknowledging ignorance, if successfully incorporated within a company’s KM strategy, will not only facilitate and enhance knowledge storage and transmission processes but will also undoubtedly play a vital role when referring to a company’s eficiency, productivity and overall performance.

Abstract Some people are exceptional at reading emotional expressions, while others struggle. Here we ask whether the way we experience emotion “on the inside” influences the way we expect emotions to be expressed in the “outside world” and subsequently our ability to read others’ emotional expressions. Across multiple experiments, incorporating discovery and replication samples, we develop EmoMap (N = 20; N = 271) and ExpressionMap (N = 98; replication N = 193) to map adults’ experiences of emotions and visual representations of others’ emotions. Some individuals have modular maps, wherein emotional experiences and visual representations are consistent and distinct—anger looks and feels different from happiness, which looks and feels different from sadness. In contrast, others have experiences and representations that are variable and overlapping—anger, happiness, and sadness look and feel similar and are easily confused for one another. Here we illustrate an association between these maps: those with consistent and distinct experiences of emotion also have consistent and distinct visual representations of emotion. Finally (N = 193), we construct the Inside Out Model of Emotion Recognition, which explains 60.8% of the variance in emotion recognition and illuminates multiple pathways to emotion recognition difficulties. These findings have important implications for understanding the emotion recognition difficulties documented in numerous clinical populations.

Background Many genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes.Design and Methods We investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 mye-loablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors.Results Patients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients’ genotype, the incidences of both overall and grades II-IV acute graft-versus-host disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs.Conclusions We conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors.

The two case studies presented explore the potential offered by in-depth qualitative analysis of students' online discussion to enhance our understanding of how students learn. Both cases are used to illustrate how the monitoring and moderation of online student group communication can open up a ‘window into learning', providing us with new insights into complex problem-solving and thinking processes. The cases offer examples of students' ‘thinking aloud' while problem-solving, showing how and why they arrived at particular outcomes and the underlying thought processes involved. It is argued that these insights into students' learning processes can in turn offer us the opportunity to adapt our own teaching practice in order to achieve a better pedagogical ‘fit' with the learning needs of our students; for example, through a more precise or more timely intervention. It is also suggested that looking through this ‘window' enables us to concentrate our assessment more closely on the process of task completion, rather than focusing solely on the end product.

Accurately and efficiently perceiving social cues such as body movements and facial expressions is important in social interaction. Accurate social perception of this kind does not solely rely on ‘bottom-up’ visual processing but is also subject to modulation by ‘top-down’ signals. For example, if instructed to look for signs of happiness rather than fear, participants are more likely to categorise facial expressions as happy – this prior expectation biases subsequent perception. Top down modulation is also important in our reactions to others. For example, top down control over imitation plays an important role in the development of smooth and harmonious social interactions. This paper highlights the importance of top-down modulation in our perception of, and reactions to, others. We discuss evidence that top-down modulation of social perception and imitation is atypical in Autism Spectrum Conditions and in schizophrenia, and we consider the effect this may have on the development of social interactions for individuals with these developmental disorders.

Purpose: The purpose of this study was to provide longitudinal prevalence rates of incontinence-associated dermatitis (IAD) in patients in an intensive care unit (ICU) and to identify patient characteristics associated with IAD development., Design: Prospective observational., Subjects and Setting: The sample comprised 351 patients aged 18 years and older in a major metropolitan public hospital ICU in Queensland, Australia., Methods: All consenting, eligible participants at risk of developing IAD underwent weekly skin inspections to determine the presence of IAD. Data were collected weekly for 52 consecutive weeks. Descriptive statistics described the study sample and logistic regression analysis was used to identify patient characteristics associated with development of IAD., Results: The weekly IAD prevalence ranged between 0% and 70%, with IAD developing in 17% (n = 59/351) of ICU patients. The odds of IAD developing increased statistically significantly with increasing age (odds ratio [OR]: 1.029, 95% confidence interval [CI]: 1.005-1.054, P = .016), time in the ICU (OR = 1.104; 95% CI: 1.063-1.147, P < .001), and Bristol Stool chart score (OR = 4.363, 95% CI: 2.091-9.106, P < .001). Patients with respiratory (OR = 3.657, 95% CI: 1.399-9.563, P = .008) and sepsis (OR = 3.230, 95% CI: 1.281-8.146, P = .013) diagnoses had increased odds of developing IAD., Conclusions: These data show the high variability of IAD prevalence over a 1-year period. Characteristics associated with the development of IAD in patients in the ICU included older age, longer lengths of ICU stay, incontinent of liquid feces, and having respiratory or sepsis diagnoses.