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This study sought to identify opportunities for improvement of an Internal Medicine (IM) resident quality improvement (QI)/patient safety (PS) program at an academic teaching hospital. The authors conducted semi-structured interviews with 15 residents and 6 attending physicians, which were analyzed from an inductive and thematic lens using NVivo software. Ethics was approved by the institution’s Research Ethics Board (File #: 6026140). Four themes emerged from this analysis. Residents and attending physicians agreed on (i) integrating QI/PS knowledge and skills into practice using active learning approaches. However, there was concern that requiring QI project completion through (ii) standardization of QI/PS education could create a barrier to clinical research required for sub-specialization. There was agreement that the (iii) QI/PS culture within the IM program was supportive and that a lack of safe reporting efficiency within the hospital, along with interprofessional discord, could cause (iv) external barriers to QI/PS training. By integrating these findings, evidence-informed and low-resource solutions could be incorporated into the QI/PS curriculum that uses minimal preparation requirements, and fulsome conversation-based exploration of QI/PS techniques within real-world clinical cases. RésuméCette étude visait à trouver des possibilités d’améliorer un programme d’amélioration de la qualité (AQ)/sécurité des patients (SP) pour les résidents en médecine interne (MI) à un hôpital universitaire. Les auteurs ont mené des entrevues semi-structurées auprès de 15 résidents et de 6 médecins traitants, lesquelles ont été analysées d’un point de vue inductif et thématique à l’aide du logiciel NVivo. Le comité d’éthique de la recherche de l’établissement a approuvé cette recherche (dossier no : 6026140). Quatre thèmes sont ressortis de cette analyse. Les résidents et les médecins traitants sont d’accord sur les éléments suivants : i) l’intégration dans la pratique des connaissances et des compétences en AQ/SP au moyen d’approches d’apprentissage actif. Toutefois, on craint que l’obligation de mener à bien le projet d’AQ par l’intermédiaire de ii) l’uniformisation de l’enseignement de l’AQ/SP ne crée un obstacle à la recherche clinique requise pour la sous-spécialisation. Les participants s’entendent pour dire iii) que la culture de l’AQ/SP au sein du programme de MI est fondée sur le soutien et que le manque d’efficacité lié aux déclarations relatives à la sécurité au sein de l’hôpital ainsi que les désaccords interprofessionnels pourraient causer iv) des obstacles externes à la formation sur l’AQ/SP. En intégrant ces constatations, des solutions fondées sur des données probantes et nécessitant peu de ressources pourraient être incorporées dans le programme d’AQ/SP qui utilise des exigences minimales en matière de préparation et une exploration approfondie des techniques d’AQ/SP sur le mode de la conversation dans le cadre de cas cliniques réels.

Opioids are potent analgesics, but their pain-relieving effects diminish with repeated use. The reduction in analgesic potency is a hallmark of opioid analgesic tolerance, which hampers opioid pain therapy. In the central nervous system, opioid analgesia is critically modulated by adenosine, a purine nucleoside implicated in the beneficial and detrimental actions of opioid medications. Here, we focus on the A3 adenosine receptor (A3 AR) in opioid analgesic tolerance. Intrathecal administration of the A3 AR agonist MRS5698 with daily systemic morphine in male rats attenuated the reduction in morphine antinociception over 7 days. In rats with established morphine tolerance, intrathecal MRS5698 partially restored the antinociceptive effects of morphine. However, when MRS5698 was discontinued, these animals displayed a reduced antinociceptive response to morphine. Our results suggest that MRS5698 acutely and transiently potentiates morphine antinociception in tolerant rats. By contrast, in morphine-naive rats MRS5698 treatment did not impact thermal nociceptive threshold or affect antinociceptive response to a single injection of morphine. Furthermore, we found that morphine-induced adenosine release in cerebrospinal fluid was blunted in tolerant animals, but total spinal A3 AR expression was not affected. Collectively, our findings indicate that spinal A3 AR activation acutely potentiates morphine antinociception in the opioid tolerant state.

Purpose: All postgraduate residency programs in Canada are transitioning to a competency-based medical education (CBME) model divided into 4 stages of training. Queen’s University has been the first Canadian institution to mandate transitioning to CBME across all residency programs, including Diagnostic Radiology. This study describes the implementation of CBME with a focus on the third developmental stage, Core of Discipline, in the Diagnostic Radiology residency program at Queen’s University. We describe strategies applied and challenges encountered during the adoption and implementation process in order to inform the development of other CBME residency programs in Diagnostic Radiology. Methods: At Queen’s University, the Core of Discipline stage was developed using the Royal College of Physicians and Surgeons of Canada’s (RCPSC) competence continuum guidelines and the CanMEDS framework to create radiology-specific entrustable professional activities (EPAs) and milestones for assessment. New committees, administrative positions, and assessment strategies were created to develop these assessment guidelines. Currently, 2 cohorts of residents (n = 6) are enrolled in the Core of Discipline stage. Results: EPAs, milestones, and methods of evaluation for the Core of Discipline stage are described. Opportunities during implementation included tracking progress toward educational objectives and increased mentorship. Challenges included difficulty meeting procedural volume requirements, inconsistent procedural tracking, improving feedback mechanisms, and administrative burden. Conclusion: The transition to a competency-based curriculum in an academic Diagnostic Radiology residency program is significantly resource and time intensive. This report describes challenges faced in developing the Core of Discipline stage and potential solutions to facilitate this process.

Background In the United Kingdom, there is a current priority for high-quality dementia care provided at home. However, home care or domiciliary care is an area where problems have been reported, in terms of a lack of consistency, coordination and appropriate responses to the specific needs of those with dementia. The views of informal carers, who often must respond to these problems when supporting relatives, are crucial in shedding light on the issues and in seeking to promote solutions. Methods This study explored the views of informal carers of those with dementia concerning home care, through a consultation using an electronic survey. The survey questions were designed by informal carers, through a public involvement group within an existing programme of dementia research. The survey elicited responses from 52 informal carers in 2017/18. The data were analysed qualitatively using framework analysis. Findings Carers’ views focused on the need for investment into meaningful personalisation, recognising the value of providing care and valuing formal carers, systemic failings of care coordination and provision and the importance of ongoing collaboration and care planning. Conclusion Based on a framework drawn from the views of informal carers themselves, this study articulated issues of concern for home care and its delivery for people with dementia. Attempts should be made to make dementia home care more consistently personalised, inclusive and collaborative with informal carers and key others involved. Further areas to explore include working conditions of formal carers and current models utilised in homecare provision.

Objective To evaluate the proportion of eligible individuals, within one health region in Ontario, who were referred for publicly funded medical and surgical weight-loss interventions (MSWLI). Design A retrospective cohort study that used primary care data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) and referral data from the Ontario Bariatric Network (OBN). Setting Primary care practices within southeastern Ontario that contribute data to CPCSSN. Participants Patients with class II (body mass index [BMI] 35.0 to 39.9 kg/m2) or III (BMI ≥ 40 kg/m2) obesity who were eligible for referral to the OBN for MSWLI. Main outcome measures Primary care data about patients within the CPCSSN database were linked to referral records within the OBN database using 3 indirect identifiers to determine the proportion of patients with class II and III obesity who were referred to the OBN for MSWLI. An adjusted multivariate logistic regression model was used to determine the most significant predictors of referral. Results Of the 87 276 patients within one health region in Ontario, 15 526 (17.8%) patients had class II or III obesity and were eligible for referral for MSWLI. Only 966 out of those 15 526 (6.2%) patients were actually referred for MSWLI. In the multivariate regression analysis, BMI had the strongest association with referral in terms of adjusted odds ratio (AOR), varying from 2.50 (95% CI 2.04 to 3.06) for a BMI of 40.0 to 44.9 kg/m2, to 5.15 (95% CI 4.21 to 6.30) for a BMI of 50.0 kg/m2 or greater. Referral was more likely for female than male patients (AOR = 2.18; 95% CI 1.86 to 2.57), those living rurally than for urban dwellers (AOR = 1.39; 95% CI 1.20 to 1.60), and those aged 30 to 39 (AOR = 1.61; 95% CI 1.24 to 2.09) and 40 to 49 (AOR = 1.53; 95% CI 1.18 to 1.98) compared with other age groups. Conclusion Within one health region in Ontario, the referral rate of patients with class II and III obesity for MSWLI was low. Our findings highlight the need for further research to understand and address the barriers to referral of patients with class II and III obesity for MSWLI.

Innovation Procurement Strategies (IPS) strive for purchasing healthcare solutions that do not yet exist on the market and are increasingly being advocated to improve health outcomes while managing escalating healthcare costs. Due to the newness of IPS, there are limited resources available to healthcare organizations and professionals looking to engage in IPS. The purpose of this study was to develop an evidence-based clinical framework to guide healthcare organizations and professionals. Adopting a qualitative grounded theory approach, we interviewed participants with experience in innovation procurement to understand the skills, resources, and supports needed to initiate and oversee an IPS project. Using thematic design and open coding, three overarching themes emerged from the data and formed the basis of our IPS clinical framework. By describing the components, skills, and supports and resources necessary for engaging in IPS, our framework addresses the knowledge gap in healthcare organizations and professionals wishing to implement IPS.

Treating chronic pain using opioids, such as morphine, is hampered by the development of opioid-induced hyperalgesia (OIH; increased pain sensitivity), antinociceptive tolerance and withdrawal which can contribute to dependence and abuse. In the central nervous system, the purine nucleoside adenosine has been implicated in beneficial and detrimental actions of morphine, but the extent of their interaction remains poorly understood. Here, we demonstrate that morphine-induced OIH and antinociceptive tolerance in rats is associated with a 2-fold increase in adenosine kinase (ADK) expression in the dorsal horn of the spinal cord (DH-SC). Blocking ADK activity in the spinal cord provided greater than 90% attenuation of OIH and antinociceptive tolerance through A3 adenosine receptor (A3AR) signaling. Supplementing adenosine signaling with selective A3AR agonists blocked OIH and antinociceptive tolerance in rodents of both sexes. Engagement of A3AR in the spinal cord with an ADK inhibitor or A3AR agonist was associated with reduced DH-SC expression of the NOD-like receptor pyrin domain-containing 3 (NLRP3; 60-75%), cleaved caspase 1 (40-60%), interleukin (IL)-1β (76-80%) and tumor necrosis factor (TNF; 50-60%). In contrast, the neuroinhibitory and anti-inflammatory cytokine IL-10 increased 2-fold. In mice, A3AR agonists prevented the development of tolerance in a model of neuropathic pain and reduced naloxone-dependent withdrawal behaviors by greater than 50%. These findings suggest A3AR-dependent adenosine signaling is compromised during sustained morphine to allow the development of morphine-induced adverse effects. These findings raise the intriguing possibility that A3AR agonists may be useful adjunct to opioids to manage their unwanted effects.

Purpose Radiation treatment planning (RTP) is a unique skill that requires interdisciplinary collaboration among radiation oncologists (ROs), dosimetrists, and medical physicists (MP) to train and assess residents. With the adoption of competency-based medical education (CBME) in Canada, it is essential residency program curricula focuses on developing competencies in RTP to facilitate entrustment. Our study investigates how radiation oncology team members’ perspectives on RTP education align with requirements of the CBME approach, and its implications for improving residency training. Methods and Materials This qualitative research study took place in the Department of Oncology at a midsize academic institution. Through convenience sampling, focus groups were conducted with radiation oncologists (n = 11), dosimetrists (n = 7), medical physicists (n = 7), and residents (n = 7). Thematic design was adopted to analyze the transcripts through open coding resulting in 3 overarching themes. Results The results identified existing strengths and weaknesses of the residency program and future opportunities to redesign the curriculum and assessment process within a CBME model. Three overarching themes emerged from the analysis: (1) the strengths of RTP in the CBME environment; (2) challenges of RTP in CBME; and (3) opportunities for change. Stakeholders were optimistic CBME will help enrich resident learning with the increased frequency and quality of competency-based assessments. Participants suggested building a library of cases and developing computer-based learning resources to provide a safe environment to develop skills in contouring, dosimetry, and plan evaluation, in accordance with CBME training. Conclusions This study identified future opportunities to redesign the RTP curriculum and assessment process within a CBME model. The need for innovative teaching and learning strategies, including case libraries, computer-based learning, and quality assessments, were highlighted in designing an innovative RTP planning curriculum.

Background Medicines management in care homes requires significant improvement. CHIPPS was a cluster randomised controlled trial to determine the effectiveness of integrating pharmacist independent prescribers into care homes to assume central responsibility for medicines management. This paper reports the parallel mixed-methods process evaluation. Method Intervention arm consisted of 25 triads: Care homes (staff and up to 24 residents), General Practitioner (GP) and Pharmacist Independent Prescriber (PIP). Data sources were pharmaceutical care plans (PCPs), pharmacist activity logs, online questionnaires and semi-structured interviews. Quantitative data were analysed descriptively. Qualitative data were analysed thematically. Results were mapped to the process evaluation objectives following the Medical Research Council framework. Results PCPs and activity logs were available from 22 PIPs. Questionnaires were returned by 16 PIPs, eight GPs, and two care home managers. Interviews were completed with 14 PIPs, eight GPs, nine care home managers, six care home staff, and one resident. All stakeholders reported some benefits from PIPs having responsibility for medicine management and identified no safety concerns. PIPs reported an increase in their knowledge and identified the value of having time to engage with care home staff and residents during reviews. The research paperwork was identified as least useful by many PIPs. PIPs conducted medication reviews on residents, recording 566 clinical interventions, many involving deprescribing; 93.8% of changes were sustained at 6 months. For 284 (50.2%) residents a medicine was stopped, and for a quarter of residents, changes involved a medicine linked to increased falls risk. Qualitative data indicated participants noted increased medication safety and improved resident quality of life. Contextual barriers to implementation were apparent in the few triads where PIP was not known previously to the GP and care home before the trial. In three triads, PIPs did not deliver the intervention. Conclusions The intervention was generally implemented as intended, and well-received by most stakeholders. Whilst there was widespread deprescribing, contextual factors effected opportunity for PIP engagement in care homes. Implementation was most effective when communication pathways between PIP and GP had been previously well-established. Trial registration The definitive RCT was registered with the ISRCTN registry (registration number ISRCTN 17847169).

To date, treatments of Osteoarthritis are not able to provide the pathology regression. In vitro models are therefore necessary to: i) investigate the mechanisms involved in the disease evolution, ii) identify pharmacological targets, and iii) perform predictive tests for new drug delivery strategies.

The presence and diversity of marine non-native species, the number of new invasions, and the impact on native communities and habitats are important metrics used to assess the health of marine ecosystems. Monitoring for marine non-native species, using traditional approaches such as rapid assessment surveys (RASs), requires taxonomic expertise and may still fail to detect rare or inconspicuous species. This study reports a validation process for a quantitative PCR (qPCR) assay based on the cytochrome oxidase 1 gene, designed to detect highly invasive tunicate Didemnum vexillum by targeting environmental DNA (eDNA) present in water samples. The D. vexillum qPCR assay showed high sensitivity, with the threshold limit of detection (LOD) and modeled LOD3 (based on triplicate qPCR reactions) estimated as 9.187 and 1.117 copies reaction–1, respectively and the limit of quantification (LOQ) was calculated as 18 copies reaction–1. Analyses of water samples collected from selected Pacific oyster farms and recreational marinas in Scotland showed 100% concordance between the historical data on presence of D. vexillum from RASs and detection of D. vexillum eDNA. Consistency of detection of D. vexillum eDNA among different sampling points within each infected sampling site varied, ranging between 100% positive throughout the site to some sampling points testing “negative” or only as “suspected” for D. vexillum. Sites with lower within-site detection consistency included sites with a low density of D. vexillum as reported by RASs or were sites undergoing D. vexillum management. The present pilot monitoring program demonstrates the potential to generate important data on presence of D. vexillum. This program will be scaled up across large geographic regions and used in the first instance to focus and target the traditional RASs to D. vexillum eDNA-positive sites in a cost-effective way, with an aim to verify the species presence by visual observation and direct Sanger sequencing of positive qPCR products.

Introduction Titanium-based fracture fixation devices often necessitate removal in the maxillofacial region. Resorbable composite implants negate the need for a revision operation; however, concurrent devices either possess a prolonged degradation profile or bioactivity, resulting in undesirable bone deposition. To that end, a novel, fast-resorbing, non-bioactive composite material is proposed, which still possesses an osteoinductive potential, thereby aiding fracture healing. Method Three bioglasses were available (NCL1-3) as filler material. NCL2 was selected and different concentrations (5%; 20%) were added to reinforce medical grade poly(lactic-co- glycolide) (PLGA). The final compression moulded samples underwent material characterisation and an 8-week degradation assay. Results No significant difference was found between the cytotoxicity of the glasses and both the positive (apatite wollastonite) and negative (absence of glass) controls in relation to mesenchymal stem cells or osteoblasts. pH and weight change analyses showed an increased rate of degradation with an increase in glass concentration. Although reinforcement with NCL2 did not increase the mechanical properties of the polymer, no significant difference was present between the mechanical properties of the composites, and, as made, both 5% and 20% composites had flexural strengths of 13MPa±5, which did not decrease significantly during degradation. Conclusions NCL1-3 are non-toxic in the context of fracture healing. The PLGA/NCL2 composite is not suitable for fracture fixation as produced currently, due to increased polymer degradation and lower mechanical properties. However, 20% compositions are recommended for future research, as they would hypothetically provide a superior osteoinductive response without significantly lowering the mechanical properties of the composite.

© The Author(s), 2020. Published by Cambridge University Press. Home care for older people in England is commissioned through local authorities working predominantly with independent providers of care. Commissioners operate in a market model, planning and procuring home care services for local populations. Their role involves 'managing' and 'shaping' the market to ensure an adequate supply of care providers. Another imperative, emerging from the principles of personalisation, is the drive to achieve user outcomes rather than 'time and task' objectives. Little formal research has investigated the way commissioners reconcile these different requirements and organise commissioning. This study investigated commissioning approaches using qualitative telephone interviews with ten commissioners from different local authorities in England. The characteristics of commissioning were analysed thematically. Findings indicated (a) commissioning involved complex systems and processes, uniquely shaped for the local context, but frequently changed, suggesting a constant need for reframing commissioning arrangements; (b) partnerships with providers were mainly transactional, with occasional examples of collaborative models, that were considered to facilitate flexible services more appropriate for commissioning for personalised outcomes; and (c) only a small number of commissioners had attempted to reconcile the competing and incompatible goals of tightly prescribed contracting and working collaboratively with providers. A better understanding of flexible contracting arrangements and the hallmarks of a trusting collaboration is required to move beyond the procedural elements of contracting and commissioning.

Construct: Competence Based Medical Education (CBME) is designed to use workplace-based assessment (WBA) tools to provide observed assessment and feedback on resident competence. Moreover, WBAs are expected to provide evidence beyond that of more traditional mid- or end-of-rotation assessments [e.g., In Training Evaluation Records (ITERs)]. In this study we investigate competence in General Internal Medicine (GIM), by contrasting WBA and ITER assessment tools.Background: WBAs are hypothesized to improve and differentiate written and numerical feedback to support the development and documentation of competence. In this study we investigate residents’ and faculty members’ perceptions of WBA validity, usability, and reliability and the extent to which WBAs differentiate residents’ performance when compared to ITERs. Approach: We used a mixed methods approach over a three-year period, including perspectives gathered from focus groups, interviews, along with numerical and narrative comparisons between WBA and ITERs in one GIM program.Results: Residents indicated that the narrative component of feedback was more constructive and effective than numerical scores. They perceived the focus on specific workplace-based feedback was more effective than ITERs. However, quantitative analysis showed that overall rates of actionable feedback, including both ITERs and WBAs, were low (26%), with only 9% providing an improvement strategy. The provision of quality feedback was not statistically significantly different between tools; although WBAs provided more actionable feedback, ITERs provided more strategies. Statistical analyses showed that more than half of all assessments came from 11 core faculty.Conclusions: Participants in this study viewed narrative, actionable and specific feedback as essential, and an overall preference was found for written feedback over numerical assessments. However, quantitative analyses showed that specific actionable feedback was rarely documented, despite qualitative emphasis from both groups of its importance for developing competency. Neither formative WBAs or summative ITERs clearly provided better feedback, and both may still have a role in overall resident evaluation. Participant views differed in roles and responsibilities, with residents stating that faculty should be responsible for initiating assessments and vice-versa. These results reveal a disconnect between resident and faculty perceptions and practice around giving feedback and emphasize opportunities for programs adopting and implementing CBME to address how best to support residents and frontline clinical teachers.

Objective As competency-based medical education (CBME) rolls out across Canada, the assessment process is changing. Our purpose was to involve stakeholders in the selection and modification of workplace-based assessment (WBA) tools for use in an ophthalmology residency program. Design This is a qualitative case study conducted in one ophthalmology department at a midsized teaching hospital in eastern Ontario. Participants Ophthalmology faculty and residents within the Emergency Eye Clinic participated in the study. Methods Phase 1 consisted of faculty piloting the tools and providing written feedback. Phase 2 consisted of 2 focus groups, 1 for residents (n = 9) and 1 for faculty (n = 6), to explore their experiences with the 4 piloted adapted WBA tools. Results Residents and faculty discussed ongoing issues with buy-in and formalizing feedback through the new assessment process. Residents also reiterated the need for more constructive feedback delivered in a timely and sensitive manner. Generally, residents did not value numerical scales on the tools and preferred written comments. Both residents and faculty valued oral over written feedback given the interactive nature of oral feedback. Conclusions This study provides insight into faculty and resident perspectives about WBA tools within one ophthalmology department. These results informed the development of WBA tools within the department and highlighted the importance of shifting the assessment culture to accommodate programmatic approaches to assessment in CBME. Involving key stakeholders in the change process has been a valuable strategy. Future research should examine whether or not these perspectives change after CBME implementation.

© 2019, © 2019 Society for Research into Higher Education. With an increase in technology to mediate learning and a shift to more student-centred approaches, open-ended online assignment tasks are becoming more common in higher education. Open-ended tasks offer opportunities for students to develop their own interpretations of the requirements, and online technologies offer greater flexibility and afford new types of interactions with teachers and other students. This paper presents a study of students' task interpretation and self-set goals in the context of five open-ended online assignment tasks. The findings presented in this paper demonstrate the importance of a high-quality task understanding for goal setting and suggest practical implications for task design and support.

Background Community Paramedics (CPs) require access to timely blood analysis in the field to guide treatment and transport decisions. Point of care testing (POCT), as opposed to laboratory analysis, may offer a solution, but limited research exists on CP POCT. The purpose of this study was to compare the validity of two devices (Abbott i-STAT® and Alere epoc®) by CPs in the community. Methods In a CP programme responding to 6000 annual patient care events, a split sample validation of POCT against traditional laboratory analysis for seven analytes (sodium, potassium, chloride, creatinine, hemoglobin, hematocrit, and glucose) was conducted on a consecutive sample of patients. The difference of proportion of discrepant results between POCT and laboratory was compared using a two sample proportion test. Usability was analysed by survey of CP experience, a linear mixed effects model of Systems Usability Scale (SUS) adjusted for CP clinical and POCT experience, an expert heuristic evaluation of devices, a review of device-logged errors, and coded observations of POCT use during quality control testing. Results Of 1649 episodes of care screened for enrollment, 174 required a blood draw, with 108 episodes (62.1%) enrolled from 73 participants. Participants had a mean age of 58.7 years (SD16.3); 49% were female. In 4 of 646 (0.6%) comparisons, POCT reported a critical value but the laboratory did not; with no statistically significant (p = 0.323) difference between i-STAT® (0.9%;95%CI:0.0,1.9%) compared with epoc® (0.3%;95%CI:0.0,0.9%). There were no instances of the laboratory reporting a critical value when POCT did not. In 88 of 1046 (8.4%) comparisons the a priori defined acceptable difference between POCT and the laboratory was exceeded; occurring more often in epoc® (10.7%;95%CI:8.1,13.3%) compared with i-STAT® (6.1%;95%CI:4.1,8.2%)(p = 0.007). Eighteen of 19 CP surveys were returned, with 11/18 (61.1%) preferring i-STAT® over epoc®. The i-STAT® had a higher mean SUS score (higher usability) compared with epoc® (84.0/100 vs. 59.6/100; p = 0.011). There were no statistically significant differences in device logged errors between i-STAT® and epoc® (p = 0.063). Conclusions CP programmes can expect clinically valid results from POCT. Device usability assessments should be considered with any local implementation as the two POCT systems have different strengths. Electronic supplementary material The online version of this article (10.1186/s12873-019-0243-4) contains supplementary material, which is available to authorized users.

The post-graduate medical programs at Queen's University transitioned to a competency-based medical education framework on July 1, 2017. In advance of this transition, the Medical Oncology program participated in a pilot of six Entrustable Professional Activities (EPAs) focused workplace-based assessment (WBA) tools with faculty and residents. The purpose of this sequential explanatory mixed method study was to determine the extent to which these WBAs provided quality feedback for residents. The WBAs were introduced into daily clinical practice and, once completed, were collected by the research team. A resident focus group (n = 4) and faculty interviews (n = 5) were also conducted. Focus group and interview data were analyzed using an emergent thematic analysis. Data from the completed assessment tools were analyzed using both descriptive statistics and a literature-informed framework developed to assess the quality of feedback. Six main findings emerged: Verbal feedback is preferred over written; providing both written and verbal feedback is important; effective feedback was seen as timely, specific, and actionable; the process was conceptualized as coaching rather than high stakes; there were logistical concerns about the WBAs, and additional clarification about the WBA tools is needed. This study provides insight into faculty and resident perceptions of quality feedback and the potential for WBA tools to assist in providing effective feedback to residents as we shift to competency-based medical education in Canada. Our results suggest the need for additional faculty development around the use of the tools, and their intended role, and the elements of quality feedback.

Simple Summary There is limited information about genomic markers, especially for cervical adenocarcinoma treatment decisions. In this prospective study, it was found that nonsynonymous PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. It is the first indication of the predictive power of PIK3CA aberration in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for the prolonged strategy of surveillance and indicates the possibility of tailoring management of this particular women’s cancer. Abstract Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

Introduction Due to the increasing global burden of cancer and the shortage of trained medical oncologists, training General Practitioners (GPs) in Oncology (known as GPOs) has been proposed as a means to potentially ease some burden on medical oncologists with heavy workloads, especially in low-and-middle-income countries (LMICs), by task-sharing and task-shifting. We undertook a scoping review to identify and characterise the existing training programmes and curricula for GPOs globally. Design We searched three major electronic databases: EMBASE, Medline/PubMed and Education Source for articles that described a medical oncology training programme for GPs. All study types were eligible in this review. We followed a two-stage standardised screening process using two independent reviewers to evaluate the eligibility of the articles. Results Five peer-reviewed articles were included in our review and grey literature scans identified an additional seven GPO training programmes for a total of 12 programmes and their curricula. All of the included studies were from high-income countries. The duration of programmes varied from comprehensive programmes structured over 2 years (n = 2) to shorter duration medical oncology training activities (n = 2), a short, 1.5-day workshop and a 10-hour course. In the grey literature, GPO training programme durations ranged from 2 weeks to 13 months. A mixture of delivery methods was employed including didactic lectures and clinical rotations. Conclusion This scoping review identified a small number of heterogeneous studies and grey literature sources that described and/or evaluated medical oncology training programmes for GPs. The information synthesised here can be used to foster the collaboration needed for the continued development of GPO programmes that could help address the problem of lack of workforce to meet the rising burden of cancer, especially in LMICs.

We introduce a novel 3D microrheology system that combines for the first time Optical Tweezers with Integrated Multiplane Microscopy (OpTIMuM). The system allows the 3D tracking of an optically trapped bead, with ~ 20 nm accuracy along the optical axis. This is achieved without the need for a high precision z-stage, separate calibration sample, nor a priori knowledge of either the bead size or the optical properties of the suspending medium. Instead, we have developed a simple yet effective in situ spatial calibration method using image sharpness and exploiting the fact we image at multiple planes simultaneously. These features make OpTIMuM an ideal system for microrheology measurements, and we corroborate the effectiveness of this novel microrheology tool by measuring the viscosity of water in three dimensions, simultaneously.

Composites offer an opportunity to couple particular benefits of their constituents to achieve unique material properties that can be of extra value in many tissue engineering applications. Strategies combining hydrogels with fibre-based scaffolds can create more biologically and structurally functional tissue constructs. However, developing efficient and scalable approaches to manufacture such composites is challenging. Here, we use a droplet-based bioprinting system called Reactive Jet Impingement (ReJI) to integrate a cell-laden hydrogel with a microfibrous mesh. The ReJI system uses microvalves that are connected to different bio-ink reservoirs and directed to continuously jet bio-ink droplets at one another in mid-air where the droplets react and form a hydrogel that lands on a microfibrous mesh. We produce cell-hydrogel-fibre composites by embedding human dermal fibroblasts at two different concentrations (5 x 106 and 30 x 106 cells/ml respectively) in a collagen-alginate-fibrin hydrogel matrix and bioprint it onto a fibre-based substrate. Our results show that both types of cell-hydrogel-microfibre composites maintain high cell viability and promote cell-cell and cell-biomaterial interactions. The lower fibroblast density thereby triggers cell proliferation whereas the higher fibroblast density facilitates faster cellular organisation and infiltration into the microfibres. Additionally, the fibrous component of the composite is characterised by its high swelling properties and quick calcium ions release. The data indicate that the composite constructs we create offer an efficient way to create highly functional tissue precursors for laminar tissue engineering in particular wound healing and skin tissue engineering applications.

We report the synthesis of a novel metal-organic capsule constructed from six pyrogallol[4]arene macrocycles, which are switched together by 16 Fe(III) and 16 Co(II) ions. This supramolecular structure represents the first instance of a spheroidal heterometallic nanocage assembled through a one-step metal-ligand coordination approach. This new assembly also demonstrates an important proof of concept through the formation of multiple heterometallic metal-metal interactions within the capsule framework. Photophysical and electrochemical studies of self-assembled capsule films indicate their potential as semiconductors. These materials display unexpected photoelectric conversion properties, thus representing an emergent phenomenon in discrete metal-organic supramolecular assemblies.

This paper reports qualitative data about violence and trauma amongst drug injectors in Scotland, collected using a life story method with 55 drug injectors currently in recovery. It focusses on different types of violence and trauma that occurred whilst using drugs. Stories told of very severe and repeated traumas often involving extreme violence. One motive for escalating and continuing drug use was avoidant coping to deaden the emotions and thoughts regarding these traumas. Many traumas were due partly to the criminal drug milieu, so respondents were in a vicious cycle of using opiates and other sedative drugs to cope with the consequences of being involved in a lifestyle of using, supplying and obtaining illegal sedative drugs. Drugs were used as a dynamic method of self-medication or avoidant coping to cope with life in a criminal milieu. Traumatic events were more often described as worsening the lifestyle than as being motives for quitting. Amongst the traumas recounted were many incidents of extreme violence. Using drugs to block the psychological effects of such traumas may help explain why people persist using opiates despite experiencing evident serious harms. Interventions need to recognise this, be trauma-aware and appreciate that violence and trauma have severe adverse effects on drug injectors even when they are themselves hardened and violent.

In England, care to support people living at home is largely commissioned by local authorities (statutory organisations with responsibility for social care in specific localities) from non-statutory home-care providers (for-profit, not-for-profit, voluntary). This paper explores how managers of these services perceive commissioning arrangements and their impact on home-care providers, the care workforce and service users. Little formal research of providers’ experiences of working with local authorities in a commissioning model is available. A qualitative study employed semi-structured telephone interviews with 20 managers of for-profit home-care providers from 10 selected local authority areas in England. Data were analysed using thematic analysis to identify main and subsidiary themes. Home-care providers reported operating in a complex and changeable partnership with commissioners, characterised by: (a) relationships ranging from transactional to collaborative, (b) providers expressing a strong sense of public service motivation, (c) commissioning practices that were complex to negotiate, time-consuming and overly prescriptive, (d) frequent changes in commissioning practices and a perceived lack of strategic planning, which were reported as contributing to uncertainty and tension for providers and confusion for service users. Attempting to operate a market model with tightly prescribed contracts is likely to be unsustainable. An alternative approach based on a collaborative model of joint responsibility for providing home care is recommended drawing on a conceptual framework of principal–steward relationships in contracting.

Background Primary care providers (PCPs) are typically the primary contact for patients with obesity seeking medical and surgical weight loss interventions; however, previous studies suggest that fewer than 7% of eligible adult patients are referred to publically funded medical and surgical weight loss interventions (MSWLI). Methods We performed an anonymous survey study between October 2017 and June 2018 to explore the knowledge, experiences, perceptions, and educational needs of PCPs in Southeastern Ontario in managing patients with class II and III obesity. Results Surveys were distributed to 591 PCPs (n = 538 family physicians; n = 53 nurse practitioners) identified as practicing in the Southeastern Ontario and 92 (15.6%) participated. PCPs serving a rural population estimated that 14.2 ± 10.9% of patients would qualify for MSWLI compared to 9.9 ± 8.5% of patients of PCPs serving an urban population (p = .049). Overall, 57.5% of respondents did not feel competent prescribing MSWLI to patients with class II/III obesity, while 69.8% stated they had ‘good’ knowledge of the referral criteria for MSWLI. 22.2% of respondents were hesitant to refer patients for bariatric surgery (BS) due to concerns about postoperative surgical complications and risks associated with surgery. Only 25% of respondents were comfortable providing long-term follow up after BS, and only 39.1% had participated in continuing education on management of patients with class II/III obesity in the past 5 years. Conclusion The majority of PCPs believe there is a need for additional education about MSWLI for patients with class II/III obesity. Future studies are needed to develop and compare the effectiveness of additional education and professional development around risks of contemporary BS, indications to consider referral for MSWLI, management and long-term follow-up of patients after BS.

Background and Objective: This review updates and expands on previous reviews of educational interventions for primary care providers (PCPs) involved in palliative and end-of-life care (PEoLC) and is the first to include early studies related to medical assistance in dying (MAiD). Methods: A comprehensive search strategy was conducted across five electronic databases to locate published interventional studies related to ongoing PEoLC and/or MAiD education for primary care professionals. A descriptive summary of results and a narrative discussion of common themes and comparisons are provided. Results: Thirty-seven studies met the inclusion criteria. The researchers found a myriad of interventions, including courses based, practical experience, mentoring, and workshops. The researchers categorized results by four domains: attitude, confidence, knowledge, and skills. Across domains, seven educational topics emerged: general care, interprofessional collaboration, nutrition, pain and symptom management, patient communication, and professional coping. Overall, studies employed various methodologies, but often relied on cross-sectionally measured self-assessment. Two articles were found that measured the impact of MAiD education. Conclusion: These findings suggest that PEoLC education can improve PCPs' perceived attitudes, confidence, knowledge, and skills across multiple areas of palliative care practice. While PCPs across studies valued educational interventions, the findings relating to the impact of PEoLC education on PCP's provision of effective PEoLC were unclear. However, most interventions resulted in enhanced confidence and knowledge. To date, there are only two studies that have examined MAiD educational programs. There is a need for studies of higher rigor with more emphasis on follow-up to clarify the impact training has on those involved in PEoLC and MAiD.

Purpose: The Royal College of Physicians and Surgeons of Canada (RCPSC) has mandated the transition of postgraduate medical training in Canada to a competency-based medical education (CBME) model divided into 4 stages of training. As part of the Queen’s University Fundamental Innovations in Residency Education proposal, Queen’s University in Canada is the first institution to transition all of its residency programs simultaneously to this model, including Diagnostic Radiology. The objective of this report is to describe the Queen’s Diagnostic Radiology Residency Program’s implementation of a CBME curriculum. Methods: At Queen’s University, the novel curriculum was developed using the RCPSC’s competency continuum and the CanMEDS framework to create radiology-specific entrustable professional activities (EPAs) and milestones. In addition, new committees and assessment strategies were established. As of July 2015, 3 cohorts of residents (n = 9) have been enrolled in this new curriculum. Results: EPAs, milestones, and methods of evaluation for the Transition to Discipline and Foundations of Discipline stages, as well as the opportunities and challenges associated with the implementation of a competency-based curriculum in a Diagnostic Radiology Residency Program, are described. Challenges include the increased frequency of resident assessments, establishing stage-specific learner expectations, and the creation of volumetric guidelines for case reporting and procedures. Conclusions: Development of a novel CBME curriculum requires significant resources and dedicated administrative time within an academic Radiology department. This article highlights challenges and provides guidance for this process.

Interest in the Scholarship of Teaching and Learning (SoTL) is driven in part by the need to provide systematic academic development for faculty anchored in evidence-based practice such as the introduction of quality assurance frameworks. This article reports on a mixed-method evaluation of one institution’s grassroots multidisciplinary faculty development program, called the Educational Research Series, to determine if it met the needs of its faculty, graduate student, and staff participants. Conducted at one mid-sized university in southern Ontario and framed, as was the program design and implementation, by both adult learning theory and constructivism, the evaluation collected data from session exit surveys, attendee interviews, and facilitator focus groups. The data analysis revealed that reasons for participating included increasing levels of understanding, receiving individual support, and learning about colleagues’ research interests. The major strengths of the program included individual learning, resources, facilitator expertise, interactive sessions, and the multidisciplinary focus. The main challenges centered on depth versus breadth of the sessions, time, and educational language and theory. Participants recommended additional resources, communication among facilitators, institutional recognition, and increased depth of content. As a result of this evaluation, an Advanced Educational Research Series is being offered at the institution. This article will inform other institutions wishing to build SoTL as a field within their institutions.

Background: Lung cancer (lc) is a complex disease requiring coordination of multiple health care professionals. A recently implemented lc multidisciplinary clinic (mdc) at Kingston Health Sciences Centre, an academic tertiary care hospital, improved timeliness of oncology assessment and treatment. This study describes patient, caregiver, and physician experiences in the mdc. Methods: We qualitatively studied patient, caregiver, and physician experiences in a traditional siloed care model and in the mdc model. We used purposive sampling to conduct semi-structured interviews with patients and caregivers who received care in one of the models and with physicians who worked in both models. Thematic design by open coding in the ATLAS.ti software application (ATLAS.ti Scientific Software Development, Berlin, Germany) was used to analyze the data. Results: Participation by 6 of 72 identified patients from the traditional model and 6 of 40 identified patients from the mdc model was obtained. Of 9 physicians who provided care in both models, 8 were interviewed (2 respirologists, 2 medical oncologists, 4 radiation oncologists). Four themes emerged: communication and collaboration, efficiency, quality of care, and effect on patient outcomes. Patients in both models had positive impressions of their care. Patients in the mdc frequently reported convenience and a positive effect of family presence at appointments. Physicians reported that the mdc improved communication and collegiality, clinic efficiency, patient outcomes and satisfaction, and consistency of information provided to patients. Physicians identified lack of clinic space as an area for mdc improvement. Conclusions: This qualitative study found that a lc mdc facilitated patient communication and physician collaboration, improved quality of care, and had a perceived positive effect on patient outcomes.

Purpose The purpose of this study is to examine changes in the nature, form and range of commissioning arrangements for home care. Design/methodology/approach Data from two discrete national surveys of English local authorities with social service responsibilities were used. In the first, undertaken in 2007, responses from 111 of the 151 local authorities (74%) were received; in the second, undertaken in 2017, responses from 109 local authorities (72%) were received. A combined data set of 79 complete cases, 52% of local authorities, was created. Percentage point differences across the two time periods were calculated and tested to identify significant changes and a systematic analysis of the free-text responses regarding intended changes to the commissioning process in each data set was undertaken. Findings Findings identified substantial changes in some aspects of the commissioning of home care in the 2007-2017 decade. Collaboration between stakeholders had increased, particularly regarding the identification of future needs. Improved conditions of service and remuneration for home care workers were evident within the commissioning process. Standardised charges for home care (regardless of time and day) had also become more widespread. Initiatives to prompt providers to deliver more personalised care were more evident. Originality/value This paper describes the evolution of commissioning arrangements for home care in localities in response to national policy initiatives. It provides guidance to commissioners in meeting the needs of current service users and emphasises the importance of collaboration with stakeholders, particularly providers, in securing future capacity.

As the population of western societies on average ages, the number of people affected by bone remodeling-associated diseases such as osteoporosis continues to increase. The development of new therapeutics is hampered by the high failure rates of drug candidates during clinical testing, which is in part due to the poor predictive character of animal models during preclinical drug testing. Co-culture models of osteoblasts and osteoclasts offer an alternative to animal testing and are considered to have the potential to improve drug development processes in the future. However, a robust, scalable, and reproducible 3D model combining osteoblasts and osteoclasts for preclinical drug testing purposes has not been developed to date. Here we review various types of osteoblast–osteoclast co-culture models and outline the remaining obstacles that must be overcome for their successful translation.

Purpose This paper aims to develop and then evaluate a novel consolidation and powder transfer mechanism for electrophotographic 3D printing, designed to overcome two longstanding limitations of electrophotographic 3D printing: fringing and a build height limitation. Design/methodology/approach Analysis of the electric field generated within electrophotographic printing was used to identify the underlying causes of the fringing and build height limitations. A prototype machine was then designed and manufactured to overcome these limitations, and a number of print runs were carried out as proof of concept studies. Findings The analysis suggested that a machine design which separated the electrostatic powder deposition of the print engine from the layer transfer and consolidation steps is required to overcome fringing and build height limitations. A machine with this build architecture was developed and proof of concept studies showed that the build height and fringing effects were no longer evident. Research limitations/implications Electrophotography (EP) was initially seen as a promising technology for 3D printing, largely because the potential for multi-material printing at high speed. As these limitations can now be overcome, there is still potential for EP to deliver a high-speed 3D printing system which can build parts consisting of multiple materials. Originality/value The analysis of EP, the new method for the transfer and consolidation of layers and the proof of concept study are all original and provide new information on how EP can be adopted for 3D printing.

Our modern-day frenetic healthcare culture has progressed to a state where healthcare professionals tend to detach themselves from the emotions of their patients/clients, rather than embed compassion into their daily practice. The AMS Phoenix Project: A Call to Caring was implemented with the goal to instil and sustain empathy and compassion in environments where clinicians learn and work. The purpose of this study is to report on how an interprofessional community of practice (CoP) of healthcare educators can contribute to a cultural shift in promoting and delivering compassion in healthcare through health professionals education. Using an imaginative creative autoethnography that adopts a narrative design through graphic illustrations, data were collected from 25 members of the Phoenix@Queen’s CoP during a 1-day retreat. Data collection included a graphic recorder who visually depicted all retreat dialogue, field notes that highlighted emergent themes and artefacts produced during the day. Audio recordings of the discussions were used as secondary sources of data. Using thematic analysis, three themes emerged: the call to caring is a long and winding road with many barriers and rewards; CoP members experienced personal growth in and through the community; and the Phoenix@Queen’s CoP matters in terms of professional relationships, leadership and moving forward a shared agenda about practising compassionate healthcare. This study describes the development of a CoP that moves away from traditional committees and discussions to an experiential creation of connections and shared meaning by its members. By using autoethnography, and by demonstrating how graphic illustration can be an innovative and creative method for recording and interpreting group discussions, we have demonstrated the accelerated development of an authentic CoP. With a richer and more authentic community, the shared goals of healthcare professional educators are more likely to be achieved.

Career planning, decision making about specialty choice, and preparation for residency matching are significant sources of stress for medical students. Attempts have been made to structure and formalize career advising by including it in accreditation standards. There is an expressed need for national guidelines on career advising for medical students. The Future of Medical Education in Canada Postgraduate (FMEC PG) Implementation Project was created to ensure Canadian medical trainees receive the best education possible. From this, a diverse sub-working group (SWG), representing different Canadian regions, was formed to review career advising processes across the country. The SWG developed, through a modified formal consensus methodology, a strategy for medical student career advising that is adaptable to all schools in alignment with existing accreditation standards. The SWG outlined five guiding principles and five essential elements for Canadian universities offering an MD degree with recommendations on how to integrate the elements into each school's career advising system. The five essential elements are a structured approach to career advising, information about available career options, elective guidance, preparation for residency applications, and social accountability. This Perspective endorses the view of the FMEC PG Implementation Project that national guidelines are important to ensure Canadian medical schools are consistently meeting accreditation standards by providing reliable and quality career advising to all medical students. The SWG's position, based on national and provincial feedback, is that these guidelines will stimulate discourse and action regarding the requirements and processes to carry out these recommendations nationwide and share across borders.

Where total anonymity and confidentiality were previously respected in drug research, a tendency towards the provision of “hard” data such as verifiable personal details seriously disadvantages researchers working with “hidden groups” who use drugs in a relatively problem free way. This particularly applies to those who use substances generally regarded as highly addictive and problematic, such as heroin. Funding for a follow-up to an earlier research project was sought; the original investigated non-problematic heroin users, whereas the chief aim of the follow-up was to examine “resilience” to the problems commonly associated with the use of heroin. An illustration of attempting to put the gathering of “hard” verifiable data into action is presented here along with the immediate consequences. Unsurprisingly, the response of potential participants to the idea of providing personal details was largely negative, as the perceived consequences of being “outed” as a heroin user were generally regarded ...

This paper reports the first study on centrifugal spinning of PHBV fibres. Fibres were spun from solution using a range of polymer concentrations, spin speeds and spinneret to collector distances. A PHBV polymer concentration of 25% w/v spun at 9000 r min − 1 produced the highest quality fibres, with fibre diameters predominantly in the 0.5–3 μm range. The rate at which fibre could be produced at the 9000 r min − 1 spin speed and with a spinneret to collector distance of 39.2 cm was equivalent to 11 km of fibre per minute per needle. Average fibre strengths of 3 MPa were achieved, together with average moduli of 100 MPa, indicating that the fibres had higher strength but lower stiffness than electrospun PHBV. The productivity and mechanical properties achieved, together with the excellent biocompatibility of PHBV, means that these fibres have potential for application in a range of biomedical applications.

This article describes a proof of concept study designed to evaluate the potential of an in vivo three-dimensional printing route to support minimally invasive repair of the musculoskeletal system. The study uses a photocurable material to additively manufacture in situ a model implant and demonstrates that this can be achieved effectively within a clinically relevant timescale. The approach has the potential to be applied with a wide range of light-curable materials and with development could be applied to create functionally gradient structures in vivo.

Within the home context a high-speed broadband Internet connection is seen as a key enabler for effective access to and use of the Internet. This article examines the factors contributing to household adoption of high speed broadband in Australia. Building on the Theory of Reasoned Action and seminal research on technology adoption in the home and the workplace, the article presents and evaluates a hypothesized model of Household Adoption of Technology.

Background Over 1 million Canadians have class II or III obesity; however, access to weight-loss interventions for these patients remains limited. The purpose of our study was to identify the barriers to accessing medical and surgical weight-loss interventions from the perspectives of 3 groups: family physicians, patients who were referred for weight-loss intervention and patients who were not referred for weight-loss intervention. Methods Between November 2017 and May 2018, we conducted a qualitative exploratory research study using focus groups with family physicians and interviews with patients with class II or III obesity from 1 region in southern Ontario. We conducted a thematic analysis to identify emergent themes and used the barriers to change theory to classify the similarities and differences between the perspectives of family physicians, referred patients and nonreferred patients in first- and second-order barriers. Results Seventeen family physicians participated in 7 focus groups (1-4 participants/group), and we interviewed 8 referred patients and 7 nonreferred patients. We identified lack of resource supports, logistics and lack of knowledge about weight-loss interventions as first-order barriers to change, and lack of knowledge about root causes of obesity, lack of patient readiness for change and family physicians' perceptions about surgical weight loss as second-order barriers to change. Family physicians and patients had similar perceptions regarding lack of resource supports in the community, logistical issues, family physicians' lack of knowledge regarding weight-loss interventions, patients' lack of motivation and family physicians' perceptions of bariatric surgery as being high risk. They differed regarding the root cause of obesity, with family physicians attributing obesity to multiple extrinsic and intrinsic causes, whereas patients believed obesity was largely due to intrinsic causes alone. Interpretation It is important to address first- and second-order barriers to accessing weight-loss interventions through continuing professional development activities for family physicians to help ensure effective and timely treatment for patients with class II or III obesity and related comorbidities.

Highlights • The tumour microenvironment promotes induction of mesenchymal stromal cells through the production of soluble factors. • Data from animal models indicates that mesenchymal stromal cells could accelerate pulmonary metastases, promote proliferation of sarcoma cells and increase chemoresistance. • Pre-activated and use of transduced mesenchymal stromal cells have a positive effect on bone sarcoma. • There is preliminary clinical evidence for mesenchymal stromal cell in promoting bone regeneration within large bone defects after surgical excision., Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cells selectively. Recently, Mesenchymal Stromal Cells (MSCs) have been the subject of significant research in orthopaedic clinical practice through their use in regenerative medicine. Further research has been directed at the use of MSCs for more personalized bone sarcoma treatments, taking advantage of their wide range of potential biological functions, which can be augmented by using tissue engineering approaches to promote healing of large defects. In this review, we explore the use of MSCs in bone sarcoma treatment, by analyzing MSCs and tumour cell interactions, transduction of MSCs to target sarcoma, and their clinical applications on humans concerning bone regeneration after bone sarcoma extraction.

Super-resolution ultrasound imaging deploys contrast microbubble (MB) tracking to delineate micro-vessels. The potential application spans to a large number of diseases which cause compromised vascular networks. Current super-resolution methods are mainly based on image processing. Sharpness-based localization is an alternative to such methods for scatterer localization in the axial direction, and can be implemented using both image and signal data. A 7-MHz, linear ultrasound transducer $(\lambda = 212 \mu \mathrm{m})$ and the Synthetic Aperture Real-time Ultrasound System (SARUS) were used to image a wire-target (point scatterer) at different depth positions. The method predicts a depth estimate and its difference from the true scatterer position demonstrates its accuracy. This average difference can be as low as $27.41 \mu \mathrm{m}($ or $\approx \lambda /8)$ for the image-derived sharpness and drops to $2.84 \mu \mathrm{m}($ or $\approx \quad \lambda /75)$ when the signals are used. These figures were calculated for a 8 mm depth range, which can be extended subject to further processing. The process of image formation involves interpolation and logarithmic compression that reduce the overall performance of the method when using image data. Such details may be significant when reconstructing micro-vessels of the order of tens of micrometres in diameter.

Additive manufacturing for microfluidics shows potential to boost research and development in research biology and molecular diagnostics. This paper reports on novel process and material optimisation techniques in the creation of a monolithic microfluidic chip geometry for polymerase chain reaction (PCR) thermocycling using stereolithography (SLA). A two-stage printing protocol with projection SLA is assessed in printing disposable oscillating-flow microfluidic cartridges for PCR. Print performance was characterized in terms of critical channel dimensions and surface quality. Post-treatment with ultraviolet light and solvent washes was shown to reduce PCR inhibiting residuals and facilitate the reaction, indicating material compatibility for fluidic and milli-fluidic PCR architectures. Residuals leaching from the polymer were shown via quantitative PCR that interact with enzyme activity. Passivation of channel surfaces with a polyethylene glycol and a silane static coating reduced the leaching interface improving overall PCR efficiency. The discussed protocols can serve as a low-cost alternative to clean-room and micromachined microfluidic prototypes for various microfluidic concepts.

This paper investigates options available to policy makers responding to the challenges of drug use in modern society, focussing on the UK. It investigates the failings of prohibition policy that has driven historic reactions to drugs, drug use and drug users globally, nationally and locally. This policy paradigm has been largely destructive and counter-productive and has led to a whole host of health and social problems. The authors have approached their investigation from a public health perspective, free from moral biases that have driven many policy initiatives until now. Many countries and regions of the world are rejecting prohibition as they move towards public health models in opposition to criminal justice responses, and this trend is continuing. Four policy models are examined; prohibition as the status quo; extension of prohibition to include alcohol and other drugs; decriminalisation; legalisation and regulation of all drugs. Each of these policy options are contested; none have universal support. However, given careful consideration, this paper proposes that our only way out of the public health and criminal justice crises that have been driven by drug policy globally is to adopt the more contentious option of legalisation and regulation of all drugs commonly used non medically.

Finite element simulations of three laminates in open-hole configuration subjected to constant amplitude tension–tension fatigue loading are investigated as part of the Damage Tolerant Design Principles program organized by the Air Force Research Laboratory. All coupons were made from unidirectional IM7/977-3 plies, which are composed of intermediate modulus carbon fibers and a toughened epoxy matrix. Government furnished experimental data from an assortment of fatigue loaded unnotched coupons were used to characterize the behavior of the composite material in the simulations. The commercial software Autodesk Helius PFA was used to model the non-linear response of the material. Blind simulations of coupon stiffness and damage at several cycle numbers and residual coupon tensile and compressive strengths are benchmarked against experimental measurements and X-rays. Upon review of the experimental results, a second round of simulations was performed where the modeling strategy was updated to improve correlation to experiment.

Finite element simulations of three laminates in open-hole and unnotched configurations subjected to tension and compression quasi-static loading are investigated as part of the Damage Tolerant Design Principles program organized by the Air Force Research Laboratory. The coupons are made from unidirectional IM7/977-3 plies, which are a composite material composed of intermediate modulus carbon fibers and a toughened epoxy matrix. Blind simulations of coupon stiffness, nominal coupon stress at failure and damage evolution are benchmarked against experimental measurements and X-rays. The blind simulations are followed by a second round of simulations where the modeling strategy is modified to improve agreement between the simulations and experiments. In the present article, the commercial software Autodesk Helius PFA is used to model the non-linear response of the composite material. Within Helius PFA, failure is evaluated at the constituent level by extracting the fiber and matrix volume average stress state from the homogenized composite stress state. The relationships between the composite and constituents are developed using multicontinuum theory and a high-fidelity micromechanics model.