Impact of COVID-19 control on lung, breast, and colorectal pathological cancer diagnoses. A comparison between the Netherlands, Aotearoa New Zealand, and Northern Ireland.

BACKGROUND: The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries. METHOD: Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017-2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population. RESULTS: Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%). CONCLUSION: The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat 'missing' patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.

Characterizing asset-based studies in public health: development of a framework.

Asset-based approaches are becoming more common within public health interventions; however, due to variations in terminology, it can be difficult to identify asset-based approaches. The study aimed to develop and test a framework that could distinguish between asset-based and deficit-based community studies, whilst acknowledging there is a continuum of approaches. Literature about asset-based and deficit-based approaches were reviewed and a framework was developed based on the Theory of Change model. A scoring system was developed for each of the five elements in the framework based on this model. Measurement of community engagement was built in, and a way of capturing how much the study involved an asset approach. The framework was tested on 13 studies examining community-based interventions to investigate whether it could characterize asset-based versus deficit-based studies. The framework demonstrated how much the principles underpinning asset-based approaches were present and distinguished between studies where the approach was deficit-based to those that had some elements of an asset-based approach. This framework is useful for researchers and policymakers when determining how much of an intervention is asset-based and identifying which elements of asset-based approaches lead to an intervention working.

Deficit-based approaches are a common approach to addressing public health issues within a community and involve identifying a health problem or need and finding a way to solve these. However, asset-based approaches, those that involve the community using its assets, or strengths, to enable community members to have more control over their health and wellbeing, are increasingly common. The terminology used to describe these methods varies greatly so it can be difficult to identify whether an approach is more deficit-based or asset-based. To address this a framework was developed to identify and score elements of asset-based studies. We did this by reviewing academic information describing asset-based approaches and built into this a scoring system. This framework was used to assess and measure the degree to which 13 community-based studies took an asset-based approach. The framework was able to identify studies which were more asset-based in their approach compared to those which were more deficit-focused, acknowledging that some studies may have elements of each approach. This framework will be useful for people working in health policy and research who want a resource to help identify asset-based approaches in practice and which aspects of the approach were important for its success in the community.

Media reporting of health interventions in New Zealand: a retrospective analysis.

AIM: To evaluate New Zealand media articles on their coverage of key issues regarding health interventions and whether it is consistent with available evidence. METHODS: A retrospective analysis was carried out of all articles published in five New Zealand media sources over a 6-week period between 15 October and 26 November 2014. Articles were included if their primary focus was on health interventions involving medications, devices or in-hospital procedures. Articles were assessed for coverage of key issues using previously validated 10-point criteria. A literature review was performed to compare content with scientific evidence. RESULTS: We identified 30 articles for review. Only 4 of 30 articles covered indications, benefits and risks, and of these, two were consistent with available evidence (7%, 95% CI 1%-22%). For articles that discussed at least one of indications, benefits or risks, and there was corresponding evidence available, there was a high level of consistency with the evidence (89%, 95% CI 77%-95%). The overall mean value of coverage from the 10-point criteria was 51% (95% CI 45%-58%). Single questions regarding the potential harm, costs associated with the intervention and the availability of alternative options were particularly poorly covered. They were rated as 'satisfactory' in 13%, 23% and 33% of the 30 articles respectively. CONCLUSION: New Zealand news articles covering medical treatments and interventions are largely consistent with available evidence but are incomplete. Vital information is being consistently missed, especially around the potential harms and costs of medical interventions.

Use of Short Animal-Themed Videos to Enhance Veterinary Students' Mood, Attention, and Understanding of Pharmacology Lectures.

Professional DVM training is inherently stressful and challenging for students. This study evaluated a simple intervention-short breaks during a veterinary pharmacology lecture course in the form of funny/cute animal videos (Mood Induction Procedures, or MIP)-to assess for potential impact on students' mood, interest in material, and perceived understanding of material. Ten YouTube video clips showing cats or dogs were selected to influence students' affective states. The videos were shown in a required pharmacology class offered during the fall semester of the second year of the DVM program at a large, land-grant institution in the western US. The student cohort consisted of 133 students (20 males, 113 females). Twenty days of the course were randomly chosen for the study and ranged from weeks 2 to 13 of the semester. Sessions in which the videos were played were alternated with sessions in which no video was played, for a total of 10 video days and 10 control days. There were significant differences in all three post-class assessment measures between the experimental (video) days and the control days. Results suggest that showing short cute animal videos in the middle of class positively affected students' mood, interest in material, and self-reported understanding of material. While the results of this study are limited to one student cohort at one institution, the ease of implementation of the technique and relatively low stakes support incorporation of the MIP technique across a variety of basic and clinical science courses.

Humanized NOG mice as a model for tuberculosis vaccine-induced immunity: a comparative analysis with the mouse and guinea pig models of tuberculosis.

The humanized mouse model has been developed as a model to identify and characterize human immune responses to human pathogens and has been used to better identify vaccine candidates. In the current studies, the humanized mouse was used to determine the ability of a vaccine to affect the immune response to infection with Mycobacterium tuberculosis. Both human CD4+ and CD8+ T cells responded to infection in humanized mice as a result of infection. In humanized mice vaccinated with either BCG or with CpG-C, a liposome-based formulation containing the M. tuberculosis antigen ESAT-6, both CD4 and CD8 T cells secreted cytokines that are known to be required for induction of protective immunity. In comparison to the C57BL/6 mouse model and Hartley guinea pig model of tuberculosis, data obtained from humanized mice complemented the data observed in the former models and provided further evidence that a vaccine can induce a human T-cell response. Humanized mice provide a crucial pre-clinical platform for evaluating human T-cell immune responses in vaccine development against M. tuberculosis.

Socioeconomic deprivation and cortical morphology: psychological, social, and biological determinants of ill health study.

OBJECTIVE: Neighborhood-level socioeconomic deprivation has been associated with poor cognitive function pertaining to language and the executive control. Few studies have explored the cortical morphology of regions most commonly associated with these functions. The aim of this study was to examine the association between neighborhood-level deprivation and the morphology of cortical regions associated with language and executive control in adults. METHODS: Using a cross-sectional study design, we compared the cortical morphology of 42 neurologically healthy adult men from the least deprived and most deprived neighborhoods of Glasgow. We performed surface-based morphometry on 3-T structural magnetic resonance imaging (MRI) images to extract the cortical morphology--volume, thickness (CT), and surface area (SA) of regions commonly associated with language and executive control. Cortical morphology was compared between the two groups. We used mediation analysis to examine whether cardiometabolic risk factors mediated the relationship between deprivation status and cortical morphology. RESULTS: Intracranial volume and mean total CT did not differ between groups. The deprived group had significantly smaller left posterior parietal cortex SA (Cohen d = 0.89) and fusiform cortex SA (Cohen d = 1.05). They also had thinner left Wernicke's area (Cohen d =0.93) and its right homologue (Cohen d = 1.12). Among the cardiometabolic markers, a composite factor comprising inflammatory markers mediated the relationship between deprivation status and Wernicke's area CT. CONCLUSIONS: A group of neurologically healthy men from deprived neighborhoods showed significantly smaller cortical morphology--both SA and CT--in regions of the brain pertaining to language and executive function. We provide additional evidence of a relationship between socioeconomic deprivation and cortical morphology.

Socioeconomic status and the cerebellar grey matter volume. Data from a well-characterised population sample.

The cerebellum is highly sensitive to adverse environmental factors throughout the life span. Socioeconomic deprivation has been associated with greater inflammatory and cardiometabolic risk, and poor neurocognitive function. Given the increasing awareness of the association between early-life adversities on cerebellar structure, we aimed to explore the relationship between early life (ESES) and current socioeconomic status (CSES) and cerebellar volume. T1-weighted MRI was used to create models of cerebellar grey matter volumes in 42 adult neurologically healthy males selected from the Psychological, Social and Biological Determinants of Ill Health study. The relationship between potential risk factors, including ESES, CSES and cerebellar grey matter volumes were examined using multiple regression techniques. We also examined if greater multisystem physiological risk index-derived from inflammatory and cardiometabolic risk markers-mediated the relationship between socioeconomic status (SES) and cerebellar grey matter volume. Both ESES and CSES explained the greatest variance in cerebellar grey matter volume, with age and alcohol use as a covariate in the model. Low CSES explained additional significant variance to low ESES on grey matter decrease. The multisystem physiological risk index mediated the relationship between both early life and current SES and grey matter volume in cerebellum. In a randomly selected sample of neurologically healthy males, poorer socioeconomic status was associated with a smaller cerebellar volume. Early and current socioeconomic status and the multisystem physiological risk index also apparently influence cerebellar volume. These findings provide data on the relationship between socioeconomic deprivation and a brain region highly sensitive to environmental factors.

The association between family and community social capital and health risk behaviours in young people: an integrative review.

BACKGROUND: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These 'risky' behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice. METHODS: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form. RESULTS: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent-child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk. CONCLUSIONS: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.

Prevalence and Risk Factors for Moral Distress in Pediatric Oncology Health Care Professionals.

PURPOSE: Moral distress (MoD) is prevalent among health care professionals (HCPs) in oncology and is associated with burnout. The objectives of this study were to quantify MoD among pediatric oncology healthcare professionals (HCPs) at a Canadian quaternary care hospital, identify root causes, and evaluate change over time. METHODS: Eligible pediatric oncology HCPs were identified, and consenting participants completed the Measure of Moral Distress-Healthcare Professionals (MMD-HP) and MoD Thermometer (MDT) at baseline, followed by biweekly MDTs over 12 weeks. RESULTS: A total of 139 HCPs participated. The mean MMD-HP score was 123 ± 57.0, range 9-288. Demographic risk factors identified for elevated MMD-HP scores were female sex (female 127.1 and male 83.6, P = .01) and nursing role (nurse 136.3 and most responsible physician 85.3, P = .02). Higher MMD-HP scores were found in HCPs who were currently considering resigning because of MoD compared with those who were not (169.9 v 115.4, P < .001). Situations involving administration of treatment to children with poor prognosis cancers that was perceived to be overly aggressive were ranked as the greatest environmental contributor to MoD. Baseline and mean MDT scores over time strongly correlated with MMD-HP scores (P < .0001 and P = .0003, respectively), with mean MDT scores showing no significant fluctuation over the 12-week period. CONCLUSION: MoD was common among pediatric oncology HCPs. Risk factors for elevated levels of MoD included both demographic and environmental factors. Implementation of systems to improve team communication and decision making, especially in the care of patients with poor prognosis cancers, may affect HCP MoD.

Common health assets protocol: a mixed-methods, realist evaluation and economic appraisal of how community-led organisations (CLOs) impact on the health and well-being of people living in deprived areas.

INTRODUCTION: This research investigates how community-led organisations' (CLOs') use of assets-based approaches improves health and well-being, and how that might be different in different contexts. Assets-based approaches involve 'doing with' rather than 'doing to' and bring people in communities together to achieve positive change using their own knowledge, skills and experience. Some studies have shown that such approaches can have a positive effect on health and well-being. However, research is limited, and we know little about which approaches lead to which outcomes and how different contexts might affect success. METHODS AND ANALYSIS: Using a realist approach, we will work with 15 CLOs based in disadvantaged communities in England, Scotland and Northern Ireland. A realist synthesis of review papers, and a policy analysis in different contexts, precedes qualitative interviews and workshops with stakeholders, to find out how CLOs' programmes work and identify existing data. We will explore participants' experiences through: a Q methodology study; participatory photography workshops; qualitative interviews and measure outcomes using a longitudinal survey, with 225 CLO participants, to assess impact for people who connect with the CLOs. An economic analysis will estimate costs and benefits to participants, for different contexts and mechanisms. A 'Lived Experience Panel' of people connected with our CLOs as participants or volunteers, will ensure the appropriateness of the research, interpretation and reporting of findings. ETHICS AND DISSEMINATION: This project, research tools and consent processes have been approved by the Glasgow Caledonian University School of Health and Life Sciences Ethics Committee, and affirmed by Ethics Committees at Bournemouth University, Queen's University Belfast and the University of East London. Common Health Assets does not involve any National Health Service sites, staff or patients.Findings will be presented through social media, project website, blogs, policy briefings, journal articles, conferences and visually in short digital stories, and photographic exhibitions.

Interaction of personality traits with social deprivation in determining mental wellbeing and health behaviours.

BACKGROUND: Associations between personality traits, mental wellbeing and good health behaviours were examined to understand further the social and psychological context of the health divide. METHODS: In a cross-sectional study, 666 subjects recruited from areas of high and low socioeconomic deprivation had personality traits and mental wellbeing assessed, and lifestyle behaviours quantified. Regression models (using deprivation as a moderating variable) assessed the extent to which personality traits and mental wellbeing predicted health behaviour. RESULTS: Deprived (vs. affluent) subjects exhibited similar levels of extraversion but higher levels of neuroticism and psychoticism, more hopelessness, less sense of coherence, lower self-esteem and lower self-efficacy (all P< 0.001). They ate less fruit and vegetables, smoked more and took less aerobic exercise (all P< 0.001). In the deprived group, personality traits were significantly more important predictors of mental wellbeing than in the least deprived group (P< 0.01 for interaction), and mental wellbeing and extraversion appeared more strongly related to good health behaviours. CONCLUSIONS: Persistence of a social divide in health may be related to interactions between personality, mental wellbeing and the adoption of good health behaviours in deprived areas. Effectiveness of health messages may be enhanced by accommodating the variation in the levels of extraversion, neuroticism, hopelessness and sense of coherence.

Investigation of test characteristics of two screening tools in comparison with a gold standard assessment to detect developmental delay at 36 months: A pilot study.

BACKGROUND: The ability of the Rourke Baby Record (Rourke) and the Nipissing District Developmental Screen (NDDS) to detect developmental delay is not known. OBJECTIVE: To determine the test characteristics of the Rourke and NDDS compared with the Bayley Scales of Infant and Toddler Development III for detecting developmental delay in high-risk children. METHODS: Three-year-olds were recruited from the IWK Health Centre (Halifax, Nova Scotia). Two cut-points were evaluated (one and two or more areas of concern) from the Rourke and NDDS, and were compared with a score of ≤85 on the Bayley Scales of Infant and Toddler Development III. RESULTS: The majority (67.7%) of the 31 participants reported no concern. At one area of concern, sensitivity was 75% for both the Rourke and NDDS. When two areas of concern were noted, specificity was 93% for the Rourke and 96% for NDDS. CONCLUSIONS: Both the Rourke and the NDDS appear to be reasonably sensitive and specific, but further investigation is warranted.

HISTORIQUE: On ne sait pas à quel point le Relevé postnatal Rourke (RPR) et le Nipissing District Developmental Screen (NDDS) peuvent déceler le retard de développement. OBJECTIF: Déterminer les caractéristiques du RPR et du NDDS par rapport aux échelles de Bayley pour le développement des nourrissons et des tout-petits III (BSITD-III) afin de déceler le retard de développement chez les enfants à haut risque. MÉTHODOLOGIE: Les chercheurs ont recruté des enfants de trois ans au IWK Health Centre (Halifax, Nouvelle-Écosse). Ils ont évalué deux seuils (1 secteur d'inquiétude et au moins 2 secteurs d'inquiétude) du RPR et du NDDS et les ont comparés à un résultat de 85 ou moins aux BSITD-III. RÉSULTATS: La majorité des 31 participants n'ont déclaré aucune inquiétude (67,7 %). Pour un secteur d'inquiétude, la sensibilité s'élevait à 75 % à la fois dans le RPR et dans le NDDS. Lorsqu'on relevait deux secteurs d'inquiétude, la spécificité s'élevait à 93 % pour le RPR et à 96 % pour le NDDS. CONCLUSIONS: Tant le RPR que le NDDS semblent être raisonnablement sensibles et spécifiques, mais des explorations plus approfondies s'imposent.

Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study.

BACKGROUND: Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. METHODS: We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. RESULTS: Associations were observed between father's occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. CONCLUSIONS: Adverse levels of biomarkers of ill health in adults appear to be influenced by father's occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the 'health divide' requires that these life course determinants are taken into account.

Pediatric hematology/oncology healthcare professional emotional health during COVID-19.

OBJECTIVES: Little is known about the impact of coronavirus disease 2019 (COVID-19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID-19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. MATERIALS AND METHODS: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID-19-positive individual and then measured outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. RESULTS: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty-nine (33.7%) had contact with a COVID-19-positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID-19-positive individual did not have significantly different outcomes. In multiple regression, non-physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. CONCLUSIONS: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID-19-positive individual was not significantly associated with outcomes. Non-physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience.

Protocol for a mixed methods study investigating the impact of investment in housing, regeneration and neighbourhood renewal on the health and wellbeing of residents: the GoWell programme.

BACKGROUND: There is little robust evidence to test the policy assumption that housing-led area regeneration strategies will contribute to health improvement and reduce social inequalities in health. The GoWell Programme has been designed to measure effects on health and wellbeing of multi-faceted regeneration interventions on residents of disadvantaged neighbourhoods in the city of Glasgow, Scotland. METHODS/DESIGN: This mixed methods study focused (initially) on 14 disadvantaged neighbourhoods experiencing regeneration. These were grouped by intervention into 5 categories for comparison. GoWell includes a pre-intervention householder survey (n = 6008) and three follow-up repeat-cross sectional surveys held at two or three year intervals (the main focus of this protocol) conducted alongside a nested longitudinal study of residents from 6 of those areas. Self-reported responses from face-to-face questionnaires are analysed along with various routinely produced ecological data and documentary sources to build a picture of the changes taking place, their cost and impacts on residents and communities. Qualitative methods include interviews and focus groups of residents, housing managers and other stakeholders exploring issues such as the neighbourhood context, potential pathways from regeneration to health, community engagement and empowerment. DISCUSSION: Urban regeneration programmes are 'natural experiments.' They are complex interventions that may impact upon social determinants of population health and wellbeing. Measuring the effects of such interventions is notoriously challenging. GoWell compares the health and wellbeing effects of different approaches to regeneration, generates theory on pathways from regeneration to health and explores the attitudes and responses of residents and other stakeholders to neighbourhood change.

Characterizing the BCG Induced Macrophage and Neutrophil Mechanisms for Defense Against Mycobacterium tuberculosis.

The live attenuated Mycobacterium bovis strain, Bacille Calmette Guérin (BCG) is a potent innate immune stimulator. In the C57BL/6 mouse model of tuberculosis, BCG vaccination leads to a significant reduction of Mycobacterium tuberculosis burden after aerogenic infection. Our studies indicated that BCG induced protection against pulmonary tuberculosis was independent of T cells and present as early as 7 days after vaccination. This protection showed longevity, as it did not wane when conventional T cell and TNF-α deficient mice were infected 30 days post-vaccination. As BCG induced mycobacterial killing after 7 days, this study investigated the contributions of the innate immune system after BCG vaccination to better understand mechanisms required for mycobacterial killing. Subcutaneous BCG inoculation resulted in significant CD11b+F4/80+ monocyte subset recruitment into the lungs within 7 days. Further studies revealed that killing of mycobacteria was dependent on the viability of BCG, because irradiated BCG did not have the same effect. Although others have identified BCG as a facilitator of trained innate immunity, we found that BCG reduced the mycobacterial burden in the absence of mechanisms required for trained innate immunity, highlighting a role for macrophages and neutrophils for vaccine induced killing of M. tuberculosis.

Lineage of measurable residual disease in patients with chronic myeloid leukemia in treatment-free remission.

Approximately half of patients with chronic myeloid leukemia (CML) in sustained deep molecular response who discontinue tyrosine kinase inhibitors (TKIs) remain in treatment-free remission (TFR). Some of these patients have measurable residual disease (MRD) by BCR-ABL1 mRNA testing, and most have detectable BCR-ABL1 DNA by highly sensitive methods. We used fluorescence-activated cell sorting and BCR-ABL1 DNA PCR to investigate the lineage of residual CML cells in TFR. Twenty patients in TFR for >1 year provided blood for sorting into granulocytes, monocytes, B cells, T cells, and NK cells. MRD was identified predominantly in the lymphoid compartment and never in granulocytes. B cells were more often BCR-ABL1 positive than T cells (18 vs 11/20 patients) and at higher levels (median 10-4.9 vs 10-5.7; P = 0.014). In 13 CML patients studied at diagnosis lymphocytes expressing BCR-ABL1 mRNA comprised a small proportion of total leukocytes. These data improve our understanding of TFR biology, since it is now clear that MRD in the blood of TFR patients need not imply the persistence of multipotent CML cells. Lineage-specific assessment of MRD could be explored as a means to improve the prediction of TFR.

Educational outreach and collaborative care enhances physician's perceived knowledge about Developmental Coordination Disorder.

BACKGROUND: Developmental Coordination Disorder (DCD) is a chronic neurodevelopmental condition that affects 5-6% of children. When not recognized and properly managed during the child's development, DCD can lead to academic failure, mental health problems and poor physical fitness. Physicians, working in collaboration with rehabilitation professionals, are in an excellent position to recognize and manage DCD. This study was designed to determine the feasibility and impact of an educational outreach and collaborative care model to improve chronic disease management of children with DCD. METHODS: The intervention included educational outreach and collaborative care for children with suspected DCD. Physicians were educated by and worked with rehabilitation professionals from February 2005 to April 2006. Mixed methods evaluation approach documented the process and impact of the intervention. RESULTS: Physicians: 750 primary care physicians from one major urban area and outlying regions were invited to participate; 147 physicians enrolled in the project. Children: 125 children were identified and referred with suspected DCD. The main outcome was improvement in knowledge and perceived skill of physicians concerning their ability to screen, diagnose and manage DCD. At baseline 91.1% of physicians were unaware of the diagnosis of DCD, and only 1.6% could diagnose condition. Post-intervention, 91% of participating physicians reported greater knowledge about DCD and 29.2% were able to diagnose DCD compared to 0.5% of non-participating physicians. 100% of physicians who participated in collaborative care indicated they would continue to use the project materials and resources and 59.4% reported they would recommend or share the materials with medical colleagues. In addition, 17.6% of physicians not formally enrolled in the project reported an increase in knowledge of DCD. CONCLUSION: Physicians receiving educational outreach visits significantly improved their knowledge about DCD and their ability to identify and diagnose children with this condition. Physicians who collaborated with occupational therapists in providing care reported more confidence in diagnosing children with DCD and were more likely to continue to use screening measures and to provide educational materials to families.

Modelling ponatinib resistance in tyrosine kinase inhibitor-naïve and dasatinib resistant BCR-ABL1+ cell lines.

TKI resistance remains a major impediment to successful treatment of CML. In this study, we investigated the emerging modes of ponatinib resistance in TKI-naïve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were increased. In the other cell line, compound mutations G250E/E255K developed with ponatinib exposure. In contrast, the ponatinib resistant cell lines that had no prior exposure to other TKIs (TKI-naïve) did not develop BCR-ABL1 KD mutations. Rather, both of these cell lines demonstrated Bcr-Abl-independent resistance via Axl overexpression. Axl, a receptor tyrosine kinase, has previously been associated with imatinib and nilotinib resistance. Ponatinib sensitivity was restored following Axl inhibition or shRNA-mediated-knockdown of Axl, suggesting that Axl was the primary driver of resistance and a potential target for therapy in this setting.