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1.
Cell ; 184(3): 810-826.e23, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33406409

ABSTRACT

Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones. We describe principles of crypt-villus axis formation; neural, vascular, mesenchymal morphogenesis, and immune population of the developing gut. We identify the differentiation hierarchies of developing fibroblast and myofibroblast subtypes and describe diverse functions for these including as vascular niche cells. We pinpoint the origins of Peyer's patches and gut-associated lymphoid tissue (GALT) and describe location-specific immune programs. We use our resource to present an unbiased analysis of morphogen gradients that direct sequential waves of cellular differentiation and define cells and locations linked to rare developmental intestinal disorders. We compile a publicly available online resource, spatio-temporal analysis resource of fetal intestinal development (STAR-FINDer), to facilitate further work.


Subject(s)
Intestines/cytology , Intestines/growth & development , Single-Cell Analysis , Endothelial Cells/cytology , Enteric Nervous System/cytology , Fetus/embryology , Fibroblasts/cytology , Humans , Immunity , Intestinal Diseases/congenital , Intestinal Diseases/pathology , Intestinal Mucosa/growth & development , Intestines/blood supply , Ligands , Mesoderm/cytology , Neovascularization, Physiologic , Pericytes/cytology , Stem Cells/cytology , Time Factors , Transcription Factors/metabolism
2.
Vox Sang ; 119(2): 155-165, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38157223

ABSTRACT

BACKGROUND AND OBJECTIVES: Using evidence from one Australian university's participation in the Vampire Cup (an 8-week national inter-university blood donation competition), this study aimed to (1) understand important motivators and successful promotional strategies driving engagement in the competition, and (2) determine the impact of competition on the recruitment and retention of young adult plasma donors. MATERIALS AND METHODS: We used a sequential explanatory mixed-methods design involving a self-administered survey (Study 1, n = 64) and four focus groups (Study 2, n = 20) with plasma donors aged 18-29 years who participated in the 2021 Vampire Cup. Also, we used a 12-month prospective comparative cohort analysis (Study 3) of those who did (n = 224 'competition donors') and did not (n = 448 control group) present to donate for the Vampire Cup. RESULTS: Competition was a strong motivator, with 76% of survey participants donating to help their university win the Vampire Cup. The survey and focus groups suggested that successful engagement in the competition was due to peer-led recruitment, leveraging existing rivalries at both the inter- and intra-university level, and using prize draws to create an active online social community promoting blood donation. Competition donors donated plasma significantly more often during the competition but donated at similar rates after the competition, compared to the control group. CONCLUSION: Rivalry-based competition strategies, combined with enthusiastic team leaders and an active social media community, can help to recruit, and retain, young adult plasma donors, and motivate an intermittent boost to donation frequency over a short period each year.


Subject(s)
Blood Donors , Motivation , Young Adult , Humans , Prospective Studies , Universities , Australia , Surveys and Questionnaires
3.
BMC Med Educ ; 24(1): 416, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627742

ABSTRACT

BACKGROUND: Professionals are reluctant to make use of machine learning results for tasks like curriculum development if they do not understand how the results were generated and what they mean. Visualizations of peer reviewed medical literature can summarize enormous amounts of information but are difficult to interpret. This article reports the validation of the meaning of a self-organizing map derived from the Medline/PubMed index of peer reviewed medical literature by its capacity to coherently summarize the references of a core psychiatric textbook. METHODS: Reference lists from ten editions of Kaplan and Sadock's Comprehensive Textbook of Psychiatry were projected onto a self-organizing map trained on Medical Subject Headings annotating the complete set of peer reviewed medical research articles indexed in the Medline/PubMed database (MedSOM). K-means clustering was applied to references from every edition to examine the ability of the self-organizing map to coherently summarize the knowledge contained within the textbook. RESULTS: MedSOM coherently clustered references into six psychiatric knowledge domains across ten editions (1967-2017). Clustering occurred at the abstract level of broad psychiatric practice including General/adult psychiatry, Child psychiatry, and Administrative psychiatry. CONCLUSIONS: The uptake of visualizations of published medical literature by medical experts for purposes like curriculum development depends upon validation of the meaning of the visualizations. The current research demonstrates that a self-organizing map (MedSOM) can validate the stability and coherence of the references used to support the knowledge claims of a standard psychiatric textbook, linking the products of machine learning to a widely accepted standard of knowledge.


Subject(s)
Algorithms , Psychiatry , Adult , Child , Humans , Machine Learning
4.
BMC Med Educ ; 24(1): 997, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39272053

ABSTRACT

BACKGROUND: Medical education offers the foundational base for future healthcare professionals, with basic sciences playing a pivotal role in providing essential knowledge and skills for clinical practice. However, the long-term retention and application of this knowledge in clinical practice remain a significant challenge. This systematic review synthesised global evidence from diverse studies on the short / long-term retention and clinical application of basic sciences among medical doctors. METHODS: A comprehensive search was conducted across six databases, including Web of Science, Scopus, Medline, CINAHL, Emcare, and Informit. The review included studies that encompassed a variety of study designs, participant groups, and educational interventions. The Quality Assessment with Diverse Studies (QuADS) tool was utilised to assess the quality of the reviewed studies. RESULTS: A total of 10 studies were included in the review. The findings revealed that rehearsals significantly optimise the retention of basic science knowledge among medical practitioners. Retention varied by discipline, with medical practitioners retaining more knowledge in anatomy (mean scores ranging from 45.0 to 82.9%), while microbiology had the lowest retention score (39.1%). Factors influencing retention included age, gender, and curriculum type. Educational interventions such as targeted courses, integration of basic sciences with clinical skills, generative retrieval and continuous quality improvement in the curriculum were found to enhance both knowledge retention and clinical reasoning. The concept of 'encapsulated knowledge' demonstrates that integrated basic science knowledge helps in synthesising clinical presentations, reducing the need for detailed recall as clinical experience increases. The reviewed studies primarily involved interns and surgeons, leaving a significant gap in research for specialties like internal medicine and primary care/ general practice. CONCLUSION: Detailed retention of basic science knowledge may diminish over time; however, the conceptual framework remains essential for ongoing learning and clinical reasoning. This review's findings highlight the need for specialised educational interventions to improve long-term retention. Continuous professional development and targeted educational techniques are vital for maintaining clinical competence and applying basic science knowledge effectively throughout a medical career. Further research is needed to address gaps in specialty-specific knowledge application and the impact of different instructional methods.


Subject(s)
Clinical Competence , Humans , Curriculum , Education, Medical , Retention, Psychology
5.
BMC Med Educ ; 24(1): 809, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075437

ABSTRACT

BACKGROUND: Basic sciences are crucial for clinical medicine, yet studies focusing on their perceived utility among general practitioners (GPs) are sparse. Considering the broad scope of GPs' practice, an in-depth understanding of basic sciences is fundamental for making informed clinical decisions. This study evaluated GP registrars' retention and perceptions of the utility of basic sciences in clinical practice. METHODS: Using sequential explanatory mixed methods study design, knowledge retention was assessed by a multiple-choice question (MCQ) examination followed by interviews on the perception of the relevance and utility of basic sciences among GP registrars at James Cook University's (JCU) General Practice Training (GPT) program. Descriptive and inferential statistical analyses were conducted on the MCQ exam data, while thematic analysis was employed for the qualitative interview data. RESULTS: Sixty-one GP registrars participated in the MCQ exam, while 11 of them were involved in the interviews. The highest mean score was obtained in biochemistry (75.1 ± 2.23) while the lowest mean score was in anatomy (56.07 ± 3.16). Key performance predictors included the formative clinical examination scores (ß = 0.83, 95% CI: 0.45 to 1.2, p < 0.001) and gender (ß = -9.7, 95% CI: -17 to -2.3, p = 0.011). The qualitative data analysis revealed five themes, including the backbone of clinical medicine, varying utility over time and by specialty, clinical synthesis integrates encapsulated knowledge, professional pressures hinder revisitation of knowledge and knowledge renewal enhances updates. CONCLUSION: Basic sciences were considered relevant in clinical practice. Development of continuing professional development (CPDs) sessions and clinically relevant online resources were measures proposed to enhance the retention of knowledge. Future research could focus on innovative educational strategies for GPs.


Subject(s)
Clinical Competence , General Practice , Humans , Male , General Practice/education , Female , Educational Measurement , General Practitioners/education , Adult , Attitude of Health Personnel , Qualitative Research
6.
Bioprocess Biosyst Eng ; 47(1): 57-64, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38156991

ABSTRACT

Biosimilars are highly complex and similar biological drugs are developed with different manufacturing processes which are not similar to originator manufacturing process. Due to this, biosimilar products inherently have quality differences in comparison to innovator molecule which may be related to size, charge and glycosylation. Despite these differences they are supposed to demonstrate similar behaviour in safety and efficacy profile to the reference product and these differences should not be clinically meaningful. Charge variants are one of the critical quality attributes and sources of heterogeneity. In this study, highly purified charge variants cluster (acidic, main peak and basic) of biosimilar product of Xolair were assessed for their impact on in vitro potency and stability at different thermal stress conditions (2-8 °C and - 20 °C). The study data indicating purified charge variants (> 90%) have no impact on in vitro potency and are stable at different thermal stress conditions up to a week.


Subject(s)
Biosimilar Pharmaceuticals , Omalizumab , Biosimilar Pharmaceuticals/pharmacology , Glycosylation
7.
Environ Geochem Health ; 46(2): 49, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38227135

ABSTRACT

The present study portrays an association between particle-bound transition metals and children's health. The indoor air quality of the urban metropolitan city households was monitored for four PM sizes, namely PM1.0-2.5, PM0.50-1.0, PM0.25-0.50 and PM<0.25, in major seasons observed in the city; summer and winter. Further transition/heavy metals, viz. Cr, Cu, Fe, Mn, Ni, Pb and Zn, were analysed in PM1-2.5 samples. In order to evaluate the effect, health risk assessment was performed using mathematical and computational model for assessing dermal exposure and dose estimation (multiple path particle dosimetry model version3.0). The study principally targeted the children aged 2-15 years for the health risk assessment. According to the results, for the largest particle size i.e. PM1.0-2.5 the highest deposition was in the head region (49.1%) followed by pulmonary (43.6%) and tracheobronchial region (7.2%), whereas, for the smallest particle size i.e. PM<0.25 the highest deposition was obtained in the pulmonary region (73.0%) followed by the head (13.6%) and TB region (13.2%). Also, the most imperilled group of children with highest dose accumulation was found to be children aged 8-9 years for all particle sizes. Moreover, the dermal exposure dose as evaluated was found to be preeminent for Ni, Zn and Pb. Besides, seasonal variation gesticulated towards elevated concentrations in winter relative to the summer season. Altogether, the study will provide a conception to the researchers in the fields mounting season-specific guidelines and mitigation approaches. Conclusively, the study commends future work focussing on defining the effects of other chemical components on particles and associated transition metal composition along with proper extenuation of the same.


Subject(s)
Air Pollution, Indoor , Transition Elements , Child , Humans , Lead , Climate , Seasons
8.
Rural Remote Health ; 24(2): 8641, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38832438

ABSTRACT

INTRODUCTION: Despite universal health coverage and high life expectancy, Japan faces challenges in health care that include providing care for the world's oldest population, increasing healthcare costs, physician maldistribution and an entrenched medical workforce and training system. Primary health care has typically been practised by specialists in other fields, and general medicine has only been certified as an accredited specialty since 2018. There are continued challenges to develop an awareness and acceptance of the primary health medical workforce in Japan. The impact of these challenges is highest in rural and island areas of Japan, with nearly 50% of rural and remote populations considered 'elderly'. Concurrently, these areas are experiencing physician shortages as medical graduates gravitate to urban areas and choose medical specialties more commonly practised in cities. This study aimed to understand the views on the role of rural generalist medicine (RGM) in contributing to solutions for rural and island health care in Japan. METHODS: This was a descriptive qualitative study. Data were collected via semi-structured interviews with 16 participants, including Rural Generalist Program Japan (RGPJ) registrars and supervisors, the RGPJ director, government officials, rural health experts and academics. Interviews were of 35-50 minutes duration and conducted between May and July 2019. Some interviews were conducted in person at the WONCA Asia-Pacific Conference in Kyoto, some onsite in hospital settings and some were videoconferenced. Interviews were recorded and transcribed. All transcripts were analysed through an inductive thematic process based on the grouping of codes. RESULTS: From the interview analysis, six main themes were identified: (1) key issues facing rural and island health in Japan; (2) participant background; (3) local demography and population; (4) identity, perception and role of RGM; (5) RGPJ experience; and (6) suggested reforms and recommendations. DISCUSSION: The RGPJ was generally considered to be a positive step toward reshaping the medical workforce to address the geographic inequities in Japan. While improvements to the program were suggested by participants, it was also generally agreed that a more systematic, national approach to RGM was needed in Japan. Key findings from this study are relevant to this goal. This includes considering the drivers to participating in the RGPJ for future recruitment strategies and the need for an idiosyncratic Japanese model of RGM, with agreed advanced skills and supervision models. Also important are the issues raised by participants on the need to improve community acceptance and branding of rural generalist doctors to support primary care in rural and island areas. CONCLUSION: The RGPJ represents an effort to bolster the national rural medical workforce in Japan. Discussions from participants in this study indicate strong support to continue research, exploration and expansion of a national RGM model that is contextualised for Japanese conditions and that is branded and promoted to build community support for the role of the rural generalist.


Subject(s)
Rural Health Services , Humans , Japan , Rural Health Services/organization & administration , Qualitative Research , Primary Health Care/organization & administration , Rural Population/statistics & numerical data , Interviews as Topic , Female , General Practice/organization & administration , Islands , Male
9.
Ann Pharm Fr ; 82(1): 64-71, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37708991

ABSTRACT

Omalizumab (Xolair) is a humanized monoclonal antibody derived by recombinant DNA technology. It binds specifically to immunoglobulin E (IgE) which plays a major role in allergic reaction by releasing histamine and other inflammatory factors from mast cells. Omalizumab binds circulatory IgE with high affinity and prevents from its binding to mast cell receptor. Charge variants are one of the critical quality attributes (CQAs) in biological drug development and sources of heterogeneity which needs to be considered in biosimilarity assessment. In this study, biosimilar product of Xolair was expressed in mammalian cell culture process in laboratory to isolate charge variants (acidic, main peak and basic). Different charge variants were isolated from intermediate purified biosimilar product of Xolair. Isolated charge variants were purified with preparative cation exchange chromatography technique and characterized with different analytical tools includes size exclusion chromatography (SEC-HPLC) and cation exchange chromatography (CEX-HPLC). Purity of acidic, main peak and basic variants was 99.58%, 99.98% and 98.64% respectively as per SEC-HPLC and according to CEX-HPLC purity was 94.25%, 95.58% and 91.33% respectively. The study data indicates that isolated charge variants were purified with desired purity and can be further used for process characterization, in vitro potency and in vivo kinetics studies.


Subject(s)
Biosimilar Pharmaceuticals , Omalizumab , Animals , Chromatography, High Pressure Liquid , Immunoglobulin E , Cations , Mammals
10.
BMC Med Educ ; 23(1): 306, 2023 May 02.
Article in English | MEDLINE | ID: mdl-37131207

ABSTRACT

BACKGROUND: Assessment of cultural safety in general practice consultations for Indigenous patients is a complex notion. Design and development of any assessment tool needs to be cognizant that cultural safety is determined by Indigenous peoples and incorporates defined components of cultural safety and current educational theory. Consideration of how social, historical, and political determinants of health and well-being impact upon the cultural safety of a consultation is also important. Given this complexity, we assume that no single method of assessment will be adequate to determine if general practice (GP) registrars are demonstrating or delivering culturally safe care. As such, we propose that development and assessment of cultural safety can be conceptualised using a model that considers these variables. From this, we aim to develop a tool to assess whether GP registrars are conducting a culturally safe consultation, where cultural safety is determined by Aboriginal and Torres Strait Islander peoples. METHODS: This protocol will be situated in a pragmatic philosophical position to explore cultural safety primarily from the Australian Aboriginal and Torres Strait Islander patients' perspective with triangulation and validation of findings with the GP and GP registrar perspective, the Aboriginal and Torres Strait Islander community, and the medical education community. The study will integrate both quantitative and qualitative data through three sequential phases. Data collection will be through survey, semi-structured interviews, an adapted nominal group technique, and a Delphi questionnaire. We aim to recruit approximately 40 patient and 20 GP participants for interviews, conduct one to five nominal groups (seven to 35 participants) and recruit fifteen participants for the Delphi process. Data will be analysed through a content analysis approach to identify components of an assessment of cultural safety for GP registrars. DISCUSSION: This study will be one of the first to explore how cultural safety, as determined by Indigenous peoples, can be assessed in general practice consultations. This protocol is shared to stimulate awareness and discussion around this significant issue and prompt other studies in this area.


Subject(s)
General Practice , Health Services, Indigenous , Humans , Australia , Cultural Competency/education , Australian Aboriginal and Torres Strait Islander Peoples , Referral and Consultation
11.
Environ Monit Assess ; 195(10): 1216, 2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37715017

ABSTRACT

Epidemiological and toxicological studies have shown the adverse effect of ambient particulate matter (PM) on respiratory and cardiovascular systems inside the human body. Various cellular and acellular assays in literature use indicators like ROS generation, cell inflammation, mutagenicity, etc., to assess PM toxicity and associated health effects. The presence of toxic compounds in respirable PM needs detailed studies for proper understanding of absorption, distribution, metabolism, and excretion mechanisms inside the body as it is difficult to accurately imitate or simulate these mechanisms in lab or animal models. The leaching kinetics of the lung fluid, PM composition, retention time, body temperature, etc., are hard to mimic in an artificial experimental setup. Moreover, the PM size fraction also plays an important role. For example, the ultrafine particles may directly enter systemic circulations while coarser PM10 may be trapped and deposited in the tracheo-bronchial region. Hence, interpretation of these results in toxicity models should be done judiciously. Computational models predicting PM toxicity are rare in the literature. The variable composition of PM and lack of proper understanding for their synergistic role inside the body are prime reasons behind it. This review explores different possibilities of in silico modeling and suggests possible approaches for the risk assessment of PM particles. The toxicity testing approach for engineered nanomaterials, drugs, food industries, etc., have also been investigated for application in computing PM toxicity.


Subject(s)
Environmental Monitoring , Particulate Matter , Animals , Humans , Particulate Matter/toxicity , Biological Assay , Computer Simulation , Kinetics
12.
Rural Remote Health ; 23(1): 8146, 2023 01.
Article in English | MEDLINE | ID: mdl-36802700

ABSTRACT

INTRODUCTION: Previous studies demonstrate early-career James Cook University (JCU) medical graduates are more likely to practise in regional, rural and remote areas than other Australian doctors. This study investigates whether these practice patterns continue into mid-career, identifying key demographic, selection, curriculum and postgraduate training factors associated with rural practice. METHODS: The medical school's graduate tracking database identified 2019 Australian practice location data for 931 graduates across postgraduate years (PGY) 5-14, which were categorised into Modified Monash Model (MMM) rurality classifications. Multinominal logistic regression was undertaken to identify specific demographic, selection process, undergraduate training and postgraduate career variables associated with practice in a regional city (MMM2), large to small rural town (MMM3-5) or remote community (MMM6-7). RESULTS: One-third of mid-career (PGY5-14) graduates were working in regional cities, mostly in North Queensland, with 14% in rural towns and 3% in remote communities. These first 10 cohorts were undertaking careers in general practice (n=300, 33%), as subspecialists (n=217, 24%), rural generalists (n=96, 11%), generalist specialists (n=87, 10%) or hospital non-specialists (n=200, 22%). DISCUSSION: The findings show positive outcomes from the first 10 JCU cohorts for regional Queensland cities, with a significantly higher proportion of mid-career graduates practising regionally compared with the overall Queensland population. The proportion of JCU graduates practising in smaller rural or remote towns is similar to the overall Queensland population. The establishment of the postgraduate JCUGP Training program and the Northern Queensland Regional Training Hubs for building local specialist training pathways should further strengthen medical recruitment and retention across northern Australia.


Subject(s)
Rural Health Services , Students, Medical , Humans , Australia , Schools, Medical , Universities , Career Choice , Professional Practice Location
13.
Rural Remote Health ; 23(1): 8147, 2023 01.
Article in English | MEDLINE | ID: mdl-36802773

ABSTRACT

INTRODUCTION: Although all James Cook University (JCU) medical students complete multiple rural placements, some undertake extended 5-10 month rural placements in their final year. This study uses return-on-investment (ROI) methodology to quantify student and rural medical workforce benefits of these 'extended placements' from 2012 to 2018. METHODS: Forty-six medical graduates were sent a survey exploring the benefits to students and to the rural workforce from participation in extended placements, as well as estimated costs to students, deadweight (how much change would have occurred without participating), and attribution (how much change was due to other experiences). The key student and rural workforce benefits were each assigned a 'financial proxy' to allow calculation of ROI as a dollar value that could be compared with the costs to students and to the medical school. RESULTS: Of the graduates, 25/46 responded (54%), reporting the major benefit was 'greater depth and breadth of clinical skills'. The overall cost of undertaking extended placements for students was $60,264 (AUD), while the medical school costs were $32,560 (total costs: $92,824). Given the total value of benefits ($705,827) calculated for the key student benefit of increased clinical skills and confidence in the internship year ($32,197) and for the key rural workforce benefit of willingness to work rurally ($673,630), the ROI from the extended rural programs is $7.60 for every dollar spent. DISCUSSION: This study confirms significant positive impacts of extended placements on final-year medical students with longer-term benefits for rural workforce. This positive ROI is important evidence for shifting the conversation around supporting extended placements from one of cost to one of value.


Subject(s)
Rural Health Services , Students, Medical , Humans , Universities , Professional Practice Location , Career Choice , Workforce
14.
Med J Armed Forces India ; 79(4): 399-408, 2023.
Article in English | MEDLINE | ID: mdl-37441289

ABSTRACT

Background: Interscalene block is usually performed using either ultrasound (US) or nerve stimulator (NS) guidance. This single-blinded, prospective, randomised study was performed to find out whether US was able to offer distinct advantages over conventional NS guidance. Methods: 100 patients in the American Society of Anaesthesiology (ASA) physical status I to III, aged 18-70 years were randomised into US guided or NS guided group for interscalene block with 15 ml 0.5% bupivacaine and 5 ml 2% lignocaine. Patients were premedicated with midazolam 0.03 mg/kg (maximum 2 mg) and fentanyl 2 mcg/kg (max 100 mcg) was used as rescue analgesia. Result: Mean time of onset of sensory block in the NS group was 6.2 min (3.1), the US group 4.7 min (1.1), p value (<0.001). Mean duration of post-operative analgesia in NS group 323.6 min (98.6), US group 558.6 min (144.3), (p < 0.001). Mean time for performance of block NS Group 7.3 min (2.0), and in the US group 4.9 min (1.3), (p < 0.001). Number of needle passes NS group 1.7(0.9), US group 1.3 (1.0), (p < 0.005). Total cost per surgery with NS was Rs 363.10 less than in the US-guided block. Incremental cost effectiveness ratio for ultrasound group for onset of block was Rs -242.07, Rs 92.0 for duration of block and Rs -151.29 for time for performance of block. No incident of post-operative neurological complications seen in either group. Conclusion: Ultrasound use offers faster onset, longer duration of block, reduces time for performance of blocks with comparable complication rates. For most of the measured parameters it was superior but more costly than nerve stimulator for directly measured costs.

15.
Gastroenterology ; 161(4): 1229-1244.e9, 2021 10.
Article in English | MEDLINE | ID: mdl-34147519

ABSTRACT

BACKGROUND & AIMS: The pathogenesis of immune checkpoint inhibitor (ICI)-colitis remains incompletely understood. We sought to identify key cellular drivers of ICI-colitis and their similarities to idiopathic ulcerative colitis, and to determine potential novel therapeutic targets. METHODS: We used a cross-sectional approach to study patients with ICI-colitis, those receiving ICI without the development of colitis, idiopathic ulcerative colitis, and healthy controls. A subset of patients with ICI-colitis were studied longitudinally. We applied a range of methods, including multiparameter and spectral flow cytometry, spectral immunofluorescence microscopy, targeted gene panels, and bulk and single-cell RNA sequencing. RESULTS: We demonstrate CD8+ tissue resident memory T (TRM) cells are the dominant activated T cell subset in ICI-colitis. The pattern of gastrointestinal immunopathology is distinct from ulcerative colitis at both the immune and epithelial-signaling levels. CD8+ TRM cell activation correlates with clinical and endoscopic ICI-colitis severity. Single-cell RNA sequencing analysis confirms activated CD8+ TRM cells express high levels of transcripts for checkpoint inhibitors and interferon-gamma in ICI-colitis. We demonstrate similar findings in both anti-CTLA-4/PD-1 combination therapy and in anti-PD-1 inhibitor-associated colitis. On the basis of our data, we successfully targeted this pathway in a patient with refractory ICI-colitis, using the JAK inhibitor tofacitinib. CONCLUSIONS: Interferon gamma-producing CD8+ TRM cells are a pathological hallmark of ICI-colitis and a novel target for therapy.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , Colitis/chemically induced , Colon/drug effects , Immune Checkpoint Inhibitors/adverse effects , Immunologic Memory/drug effects , Interferon-gamma/metabolism , Memory T Cells/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/metabolism , Case-Control Studies , Colitis/drug therapy , Colitis/immunology , Colitis/metabolism , Colitis, Ulcerative/immunology , Colitis, Ulcerative/metabolism , Colon/immunology , Colon/metabolism , Cross-Sectional Studies , Gene Expression Profiling , Humans , Longitudinal Studies , Lymphocyte Activation/drug effects , Memory T Cells/immunology , Memory T Cells/metabolism , Phenotype , Piperidines/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Prospective Studies , Pyrimidines/therapeutic use , RNA-Seq , Single-Cell Analysis , Transcriptome
16.
Environ Res ; 214(Pt 1): 113801, 2022 11.
Article in English | MEDLINE | ID: mdl-35787367

ABSTRACT

A year-long sampling campaign of ambient PM2.5 (particulate matter with aerodynamic diameter ≤2.5 mm) at a regional station in the North-Eastern Region (NER) of India was performed to understand the sources and formation of carbonaceous aerosols. Mass concentration, carbon fractions (organic and elemental carbon), and stable carbon isotope ratio (δ13C) of PM2.5 were measured and studied along with cluster analysis and Potential Source Contribution Function (PSCF) modelling. PM2.5 mass concentration was observed to be highest during winter and post-monsoon seasons when the meteorological conditions were relatively stable compared to other seasons. Organic carbon (OC) concentration was more than two times higher in the post-monsoon and winter seasons than in the pre-monsoon and monsoon seasons. Air mass back trajectory cluster analysis showed the dominance of local and regional air masses during winter and post-monsoon periods. In contrast, long-range transported air masses influenced the background site in pre-monsoon and monsoon. Air mass data and PSCF analysis indicated that aerosols during winter and post-monsoon are dominated by freshly generated emissions from local sources along with the influence from regional transport of polluted aerosols. On the contrary, the long-range transported air masses containing aged aerosols were dominant during pre-monsoon. No significant variability was observed in the range of δ13C values (-28.2‰ to -26.4‰) during the sampled seasons. The δ13C of aerosols indicates major sources to be combustion of biomass/biofuels (C3 plant origin), biogenic aerosols, and secondary aerosols. The δ13C variability and cluster/PSCF modelling suggest that aged aerosols (along with enhanced photo-oxidation derived secondary aerosols) influenced the final δ13C during the pre-monsoon. On the other hand, lower δ13C in winter and post-monsoon is attributed to the freshly emitted aerosols from biomass/biofuels.


Subject(s)
Air Pollutants , Aerosols , Biofuels , Carbon , Environmental Monitoring , India , Particulate Matter , Seasons
17.
BMC Med Educ ; 22(1): 652, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-36042497

ABSTRACT

INTRODUCTION: Rural placements are an important component of rural medical education programs seeking to develop rural practice pathways for medical students. These placements are usually domestic, but James Cook University in Australia developed an international rural placement program in the first half of the medical course that was funded through bursaries. This study explores how the international rural placement helped to shape the lives (personal development and learning) of the participants, using Transformational Learning Theory as a framework for identifying and describing the transformational elements, process and impact of the program. METHODS: Sixty-five students received a bursary for an international rural placement between 2001-2019. All were contacted by email and invited to participate in a short survey and a follow-up interview. Fifteen participants agreed and twelve were able to participate in individual semi-structured interviews which were recorded, transcribed and analysed using inductive thematic analysis. RESULTS: Participants reported that the bursary provided a "once in a lifetime opportunity" to "experience eye-opening and culturally rich difference". Nonetheless, some elements of the placement experience presented disorientating dilemmas that triggered deep reflections and shifts in perceptions. The bursary recipients realised that "being open-minded" allowed them "enjoy good company". They were also able to assume "outsider view which allowed reassessment of their own country" and the "isolation experiences gingered desire to right health wrongs". The triggers and mental shifts had significant impact on the bursary recipients and fostered the development of "inspirational new horizons" based on an appreciation of the "value of rural practice" and "role-modelling for life-long learning." These findings are consistent with Transformational Learning Theory. CONCLUSION: Participants in this study reported meaningful and strongly positive impacts from the experiences gained during an international rural clinical placement early in their course. They described transformative experiences which appear to contribute strongly to personal development. This finding supports maintaining opportunities for international experiences during rurally-oriented medical programs as these may impact longer term career choice.


Subject(s)
Rural Health Services , Students, Medical , Career Choice , Humans , Rural Population , Workforce
18.
Med Educ ; 55(3): 344-353, 2021 03.
Article in English | MEDLINE | ID: mdl-32810334

ABSTRACT

BACKGROUND: Objective structured clinical examinations (OSCEs) are commonly used to assess the clinical skills of health professional students. Examiner judgement is one acknowledged source of variation in candidate marks. This paper reports an exploration of examiner decision making to better characterise the cognitive processes and workload associated with making judgements of clinical performance in exit-level OSCEs. METHODS: Fifty-five examiners for exit-level OSCEs at five Australian medical schools completed a NASA Task Load Index (TLX) measure of cognitive load and participated in focus group interviews immediately after the OSCE session. Discussions focused on how decisions were made for borderline and clear pass candidates. Interviews were transcribed, coded and thematically analysed. NASA TLX results were quantitatively analysed. RESULTS: Examiners self-reported higher cognitive workload levels when assessing a borderline candidate in comparison with a clear pass candidate. Further analysis revealed five major themes considered by examiners when marking candidate performance in an OSCE: (a) use of marking criteria as a source of reassurance; (b) difficulty adhering to the marking sheet under certain conditions; (c) demeanour of candidates; (d) patient safety, and (e) calibration using a mental construct of the 'mythical [prototypical] intern'. Examiners demonstrated particularly higher mental demand when assessing borderline compared to clear pass candidates. CONCLUSIONS: Examiners demonstrate that judging candidate performance is a complex, cognitively difficult task, particularly when performance is of borderline or lower standard. At programme exit level, examiners intuitively want to rate candidates against a construct of a prototypical graduate when marking criteria appear not to describe both what and how a passing candidate should demonstrate when completing clinical tasks. This construct should be shared, agreed upon and aligned with marking criteria to best guide examiner training and calibration. Achieving this integration may improve the accuracy and consistency of examiner judgements and reduce cognitive workload.


Subject(s)
Clinical Competence , Educational Measurement , Australia , Humans , Physical Examination , Schools, Medical
19.
Med Teach ; 43(1): 93-100, 2021 01.
Article in English | MEDLINE | ID: mdl-33016806

ABSTRACT

OBJECTIVE: The James Cook University (JCU) medical school has a mission to produce graduates committed to practising with underserved populations. This study explores the views of final-year students regarding the influence of the JCU medical curriculum on their self-reported commitment to socially-accountable practice, intentions for rural practice, and desired postgraduate training pathway. METHODS: Cross-sectional survey of final year JCU medical students (n = 113; response rate = 65%) to determine whether their future career directions (intentions for future practice rurality and postgraduate specialty training pathway) are driven more by altruism (commitment to socially accountable practice/community service) or by financial reward and/or prestige. RESULTS: Overall, 96% of responding students reported their JCU medical course experiences had cultivated a greater commitment towards 'socially-accountable' practice. A commitment to socially-accountable practice over financial reward and/or prestige was also significantly associated with preferring to practise Medicine in non-metropolitan areas (p = 0.036) and intending to choose a 'generalist' medical discipline (p = 0.003). CONCLUSIONS: The findings suggest the JCU medical curriculum has positively influenced the commitment of its graduating students towards more socially accountable practice. This influence is a likely result of pre-clinical teachings around health inequalities and socially-accountable medical practice in combination with real-world, immersive experiences on rural and international placements.


Subject(s)
Rural Health Services , Students, Medical , Career Choice , Cross-Sectional Studies , Curriculum , Humans , Intention , Professional Practice Location
20.
BMC Med Educ ; 21(1): 28, 2021 Jan 07.
Article in English | MEDLINE | ID: mdl-33413349

ABSTRACT

BACKGROUND: The Australian Medical Council, which accredits Australian medical schools, recommends medical leadership graduate outcomes be taught, assessed and accredited. In Australia and New Zealand (Australasia) there is a significant research gap and no national consensus on how to educate, assess, and evaluate leadership skills in medical professional entry degree/programs. This study aims to investigate the current curricula, assessment and evaluation of medical leadership in Australasian medical degrees, with particular focus on the roles and responsibilities of medical leadership teachers, frameworks used and competencies taught, methods of delivery, and barriers to teaching leadership. METHODS: A self-administered cross-sectional survey was distributed to senior academics and/or heads or Deans of Australasian medical schools. Data for closed questions and ordinal data of each Likert scale response were described via frequency analysis. Content analysis was undertaken on free text responses and coded manually. RESULTS: Sixteen of the 22 eligible (73%) medical degrees completed the full survey and 100% of those indicate that leadership is taught in their degree. In most degrees (11, 69%) leadership is taught as a common theme integrated throughout the curricula across several subjects. There is a variety of leadership competencies taught, with strengths being communication (100%), evidence based practice (100%), critical reflective practice (94%), self-management (81%), ethical decision making (81%), critical thinking and decision making (81%). Major gaps in teaching were financial management (20%), strategic planning (31%) and workforce planning (31%). The teaching methods used to deliver medical leadership within the curricula are diverse, with many degrees providing opportunities for leadership teaching for students outside the curricula. Most degrees (10, 59%) assess the leadership education, with one-third (6, 35%) evaluating it. CONCLUSIONS: Medical leadership competencies are taught in most degrees, but key leadership competencies are not being taught and there appears to be no continuous quality improvement process for leadership education. There is much more we can do as medical educators, academics and leaders to shape professional development of academics to teach medical leadership, and to agree on required leadership skills set for our students so they can proactively shape the future of the health care system.


Subject(s)
Leadership , Schools, Medical , Australasia , Australia , Cross-Sectional Studies , Curriculum , Humans , New Zealand
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