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A network meta-analysis of efficacy and safety of adjuvant targeted therapy or immunotherapy in non-small cell lung cancer
No full textThe integration of targeted therapy and immunotherapy into adjuvant treatments for early-stage non-small cell lung cancer (NSCLC) remains challenging. This study aimed to compare the efficacy and safety of all available adjuvant treatment options. Randomized controlled trials (RCTs) published up to August 15, 2023, were identified from MEDLINE, Scopus, and Cochrane CENTRAL. RCTs were included if they studied early-stage NSCLC and compared any adjuvant systemic targeted therapy or immunotherapy with adjuvant chemotherapy/placebo. This study was registered with PROSPERO, CRD42022351290. Individual patient data were generated based on data extracted from Kaplan-Meier curves. A parametric survival model was used to estimate the median time for disease-free survival (DFS) and overall survival (OS). A two-stage network meta-analysis (NMA) was applied to estimate the hazard ratio (HR) for DFS and OS, in addition to the risk ratio (RR) of severe adverse events (SAE). Nineteen RCTs (n = 9,438) were included for assessing the effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), vascular endothelial growth factor (VEGF) inhibitors, immune checkpoint inhibitor (ICI) immunotherapy, and non-ICI immunotherapy. DFS in EGFR-TKIs and ICI immunotherapy was longer than chemotherapy/placebo, with a median time of 69.24, 53.47, and 39.49 months, respectively. EGFR-TKIs had a 46% significantly lower risk of recurrence [HR = 0.54 (95% CI: 0.38, 0.77)] than chemotherapy/placebo. Both EGFR-TKIs and ICI immunotherapy appeared to improve OS compared to chemotherapy or placebo, but both treatments also had an increased risk of SAE; however, neither result was statistically significant. This study indicates that EGFR-TKIs might be the best treatment regimen for reducing recurrence with an intermediate risk of SAE.</p
Effects of city design on transport mode choice and exposure to health risks during and after a crisis: a retrospective observational analysis
No full textBackgroundRapid declines in city mobility during the early stages of the COVID-19 pandemic in 2020 resulted in reductions in citizens’ exposure to transport-related air pollution and associated health risks as many cities introduced non-pharmaceutical interventions designed to curb the spread of COVID-19. However, these benefits soon reversed during the pandemic's recovery phase (ie, from September, 2020, onwards), especially in cities with designs that afforded mode shifts away from public and active transport in favour of private motor vehicles. The aim of this study was to understand the association between global city designs, transport mode choices, and population-level risk exposure during 2020.MethodsIn this retrospective observational analysis, we assembled and analysed spatial datasets (including historical and predicted pollution levels, mobility indicators, and measures of individual disease transmission) and clustered 507 global cities using a graph neural network approach based on measures of the structural dimensions of each individual city's design and network structures of urban transportation systems. We compared city types on the basis of transportation mode shifts, air pollution levels, and associated health outcomes (ie, cardiovascular disease, ischaemic heart disease, respiratory disease, asthma, and reported COVID-19 cases) throughout 2020. We estimated risk reductions for these health outcomes across four phases of the pandemic, which we defined as the pre-pandemic, entry, mid-crisis, and recovery phases. We also identified city designs showing sustained reductions at the end of 2020 in transport-related air pollution (fine particulate matter [PM2·5] and nitrogen dioxide [NO2]) associated with reduced estimated risk of acute and chronic disease outcomes (ie, all-cause mortality, ischaemic heart disease mortality, cardiovascular disease, respiratory disease, and asthma).FindingsThe mean estimated reduction of global NO2 concentrations across the observed cities from the beginning of the entry phase until the mid-crisis phase was 3·76 parts per billion (ppb), calculated as the difference between observed 2020 mean levels of 12·63 ppb and predicted mean levels (if the pandemic and mobility restrictions had not occurred) of 16·39 ppb. The mean estimated reduction of global PM2·5 concentrations across the observed cities was 9·76 μg/m3 (the difference between observed 2020 mean levels [29·03 μg/m3] and predicted mean levels [38·79 μg/m3]). If maintained over the long term, the estimated NO2 reduction could have a substantial effect on reducing health risks for both acute and chronic disease, equating to an estimated overall reduction in all-cause mortality risk of 1·5% (95% CI 2·2–3·0), a reduction in cardiovascular mortality risk of 4·1% (2·6–6·0), and a reduction in respiratory disease mortality risk of 1·9% (0·8–3·0). If the reduction in PM2·5 concentration estimated in this period was maintained over the long term, all-cause mortality risk reductions of 18·9% (95% CI 13·2–25·0), asthma risk reductions of 46·8% (18·7–65·5), and ischaemic heart disease morbidity risk reductions of 0·25% (0·2–0·3) could be achieved. In the later stages of 2020, city designs (primarily in the Americas and Oceania) that afforded a mode shift away from public transit to private motor vehicles during the pandemic's recovery phase tended to show the poorest outcomes across all air pollution and health measures, even increasing risk levels above pre-pandemic baselines in some cases. By contrast, cities located in Japan and South Korea showed little change in pre-crisis and post-crisis transport mode choice, maintaining comparatively low levels of air pollution and associated disease risk, and reduced rates of infectious disease transmission throughout the 2020 observation period. Contrasting experiences of road injury in the post-pandemic phase (ie, post 2020) were also observed between these locations.InterpretationOur results highlight the transient environmental and health benefits observed during the early stages of the COVID-19 pandemic, driven by substantial reductions in transport-related air pollution and associated health risks due to imposed non-pharmaceutical public health interventions. City design appears to have played a crucial role in observed pollution and health risk differences between cities, with those that afforded a shift away from public and active transport towards private vehicles witnessing a rapid erosion of pollution-related health benefits gained in the entry to mid-crisis phases of the pandemic. These negative effects appear to have also transferred through to increased rates of road trauma in these cities, with a resurgence in road injury above pre-pandemic levels, particularly within countries reliant on private motorised transport. Conversely, cities in Japan, South Korea, and some European regions, which did not experience modal shifts towards cars, sustained their reductions in air pollution and have continued along a trend of declining road transport injuries. These findings underscore city design as a key factor in navigating pandemic-related challenges and suggest that city designs with higher levels of public and mass transit show greater levels of resilience when confronted with infectious disease threats
Calcium in a supernova remnant as a fingerprint of a sub-Chandrasekhar-mass explosion
No full textType Ia supernovae play a fundamental role as cosmological probes of dark energy and produce more than half of the iron in our Galaxy. Despite their central importance, a comprehensive understanding of their progenitor systems and triggering mechanism is still a long-standing fundamental problem. Here we present high-resolution integral field spectroscopic observations of the young supernova remnant SNR 0509-67.5 in the Large Magellanic Cloud. We uncover a double-shell morphology of highly ionized calcium [Ca XV] and a single shell of sulphur [S XII], observed in the reverse shocked ejecta. Our analysis reveals that the outer calcium shell originates from the helium detonation at the base of the outer envelope, while the inner shell is associated with the carbon–oxygen core detonation. This morphological distribution of intermediate-mass elements agrees qualitatively with the predicted signature of the double detonation of a sub-Chandrasekhar-mass white dwarf from a hydrodynamical explosion simulation. Our observations reveal two distinct, spatially separated peaks in surface brightness of [Ca XV] from the supernova remnant phase, providing substantial evidence that sub-Chandrasekhar-mass explosions through the double-detonation mechanism could occur in nature. They also highlight the importance of remnant tomography in understanding explosion mechanisms from the remnant phase
The application of flipped classroom strategies in medical education: a review and recommendations
No full textThe role of a flipped classroom (FC) instructional method has been expanding in medical education. Despite recent interest in FC pedagogy, little is known about optimal FC implementation strategies in medical education and their impact on learning outcomes. This article aimed to outline the educational theories that guide the design of the flipped instruction method and review the relevant literature to provide evidence-based recommendations for planning, designing, developing, implementing, and evaluating FC instruction in medical education. The review incorporates evidence-based literature that highlights students’ performance outcomes and perceptions of the FC instruction method in medical education.<br/
Embedding net zero practice and managing the decarbonising of built environments: domains of nudging, tugging and mooring change
No full textDecarbonising the economy has drawn more academic management research attention in recent years. Policy practitioners such as the UK Climate Change Commission (2022) frequently review and report on the net zero transition. Significantly, it is identified that scarce progress has been made on the transition towards the decarbonising of built environments. There is therefore a significant challenge for the built environment such as the retail and distribution trades to reduce both carbon in build and also carbon in use. The immense complexity and related gaps in knowledge on ‘how to do this’ for moderately heated/cooled built environments makes it vital to understand strategic pathway frameworks. This paper contributes to the scientific net zero conversation and the need to embed net zero practice as well as manage the strategic change associated with the decarbonisation challenge. Our findings underline the opportunity for strategically orientating towards the institutional market transition, including technology cycle, collective mobilization, affirmation and innovation. We develop an overarching practice framework of how efforts to embed and manage net zero practice form and reflect domains of pushing (nudges), pulling (tugs) and mooring (tyes) practice in the overall market transitions
Quercetin loaded polymeric dissolving microarray patches: fabrication, characterisation and evaluation
No full textQuercetin, a natural compound, shows promising potential in wound healing by reducing fibrosis, limiting scar formation, and boosting fibroblast proliferation. However, its effectiveness is hindered by poor solubility, resulting in low bioavailability and necessitating high doses for therapeutic efficacy. This study presents a novel approach, fabricating quercetin-loaded microarray patches (MAPs) using widely employed solubility enhancement strategies. Fabricated MAPs exhibited favourable mechanical strength and could be inserted into excised porcine skin to a depth of 650 μm. Furthermore, formulations containing Soluplus® significantly increased the drug loading capacity, achieving up to 2.5 mg per patch and complete dissolution within an hour of application on excised porcine skin. In vitro studies on full-thickness neonatal porcine skin demonstrated that Soluplus®-enhanced MAPs effectively delivered quercetin across various skin layers, achieving a delivery efficiency exceeding 80% over 24 h. Additionally, these prototype MAPs displayed anti-inflammatory properties and demonstrated biocompatibility with human keratinocyte skin cells. Therefore, quercetin-loaded MAPs employing Soluplus® as a solubility enhancer present a promising alternative strategy for wound healing and anti-inflammatory therapy applications.<br/
Clinical decision support systems in adults with chronic respiratory disease: a systematic review
No full textBackground: Clinical decision support systems (CDSS) are systems which analyse and present data so that users can make decisions more easily and are suggested as part of the solution to poor adoption of guidelines.Aims: The aim of this review was to describe the literature on CDSS in chronic respiratory disease management, their function and the features that may impact their effectiveness.Methods: The electronic databases PubMed, MEDLINE, EMBASE, Web of Science, the trial registries Cochrane Central Register of Controlled Trials, EU Clinical Trial Register, ClinicalTrials. gov and World Health Organisation (WHO) trial registry were searched with the aid of a medical librarian. All searches began from September 2019 to March 2021.Data from relevant studies were extracted independently by 2 review authors using Covidence software and Microsoft Excel. Study quality was assessed. CDSS description and indication, function and the theory underpinning the CDSS (e.g., guidelines, expert opinion, etc.) were themed and summarised. The presence or absence of the important CDSS features were recorded i.e., (i) computer-based decision support, (ii) automatic provision of decision support as part of clinician workflow, (iiii) provision of decision support at the time and location of decisionmaking and (iv) provision of recommendations rather than just assessments.Results: Of the 2647 articles screened, 27 papers or abstracts (n = 22 full text and n = 5 abstracts) describing 26 studies met all inclusion and exclusion criteria.The 26 studies evaluated asthma care (n = 16), COPD care (n = 9) and both asthma and COPD care (n = 1). The highest level of evidence was generated by RCTs (n = 7).The 26 studies described 24 different CDSS. Most were based solely or in part on clinical and best practice guidelines. Whilst most CDSS had multiple functions, which were wide ranging, medicines management was the most prevalent function. Most systems had 3 out of 4 of the specific system features that have been correlated with improvements in clinical practice.Generally, in both controlled studies and in other study designs, patient and process outcome measures were commonly reported with performance outcomes measures less commonly reported. Fewer positive effects were reported in the higher quality studies (i.e., controlled studies). The success rate of the CDSS was higher in those studies that had 3 out of the 4 important CDSS features.Conclusion: This review demonstrates that CDSS can improve chronic respiratory disease management processes, performance and clinical outcomes in adult patients with asthma and COPD. Results from non-controlled study designs provided valuable information on important process and performance outcomes, including healthcare utility
‘The mendacious Irish character:’ Molly Maguire, anti-Irish sentiment, and anti-labor propaganda in the American press, 1880–1920
No full textThis paper evaluates the prevalence and impact of nativist and anti-labor narratives built on the claim that the ‘Molly Maguires’, a vague 1860s and 70s militant Irish labor phenomenon of the Pennsylvania anthracite region, was still active between the 1880s and the 1910s. It finds that such narratives were widespread until the late 1890s, and still regionally significant until the late 1900s, finally fading into obscurity in the 1910s. ‘Molly Maguirism’ as a media narrative was primarily directed at organized labor and the (Irish) working class; it is best understood as a form of ethnicized proto-Red Scare tactic, but could incorporate other elements, such as broader nativist ideology and sectarianism. Based on these findings, prevailing models of Irish acculturation, such as Painter’s ‘second enlargement of whiteness’, are obsolete; the paper recommends a thorough revision of late nineteenth- and early twentieth-century Irish American working-class history, accounting for the continued and hitherto massively underestimated presence of anti-Irish sentiment.<br/
Geo-political bias in fake news detection AI: the case of affect
No full textThere have been massive advances in AI technologies towards addressing the contemporary challenge of fake news identification. However, these technologies, as observed widely, have not had the same kind or depth in impact across global societies. In particular, the AI scholarship in fake news detection arguably has not been as beneficial or appropriate for Global South, bringing geo-political bias into the picture. While it is often natural to think of data bias as the potential reason for geo-political bias, other factors could be much more important in being more latent, and thus less visible. In this commentary, we investigate as to how the facet of affect, comprising emotions and sentiments, could be a potent vehicle for geo-political biases in AI. We highlight, through assembling and interpreting insights from literature, the overarching neglect of affect across methods for fake news detection AI, and how this could be a potentially important factor for geo-political bias within them. This exposition, we believe, also serves as a first effort in understanding how geo-political biases work within AI pipelines beyond the data collection stage.<br/
Inter-school variations in the standard of examiners’ graduation-level OSCE judgements
No full textINTRODUCTION: Ensuring equivalence in high-stakes performance exams is important for patient safety and candidate fairness. We compared inter-school examiner differences within a shared OSCE and resulting impact on students' pass/fail categorisation.METHODS: The same 6 station formative OSCE ran asynchronously in 4 medical schools, with 2 parallel circuits/school. We compared examiners' judgements using Video-based Examiner Score Comparison and Adjustment (VESCA): examiners scored station-specific comparator videos in addition to 'live' student performances, enabling 1/controlled score comparisons by a/examiner-cohorts and b/schools and 2/data linkage to adjust for the influence of examiner-cohorts. We calculated score impact and change in pass/fail categorisation by school.RESULTS: On controlled video-based comparisons, inter-school variations in examiners' scoring (16.3%) were nearly double within-school variations (8.8%). Students' scores received a median adjustment of 5.26% (IQR 2.87-7.17%). The impact of adjusting for examiner differences on students' pass/fail categorisation varied by school, with adjustment reducing failure rate from 39.13% to 8.70% (school 2) whilst increasing failure from 0.00% to 21.74% (school 4).DISCUSSION: Whilst the formative context may partly account for differences, these findings query whether variations may exist between medical schools in examiners' judgements. This may benefit from systematic appraisal to safeguard equivalence. VESCA provided a viable method for comparisons.</p