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Dupilumab treatment restores epithelial barrier in nonlesional and lesional skin in children with atopic dermatitis
No full textBackground
Skin barrier dysfunction and inflammation characterize both lesional and nonlesional skin in moderate-to-severe atopic dermatitis (AD) and are associated with relapses and atopic march progression.
Objective
To assess the effects of dupilumab treatment on skin barrier function and integrity using non-invasive methods in children aged 6–11 years with moderate-to-severe AD compared to matched healthy volunteers.
Methods
Patients received dupilumab for 16 weeks. Transepidermal water loss (TEWL) before (basal) and after skin tape-stripping (STS), and epidermal thickness (TE), measured by optical coherence tomography, were assessed through week 28.
Results
PELISTAD enrolled 23 patients and 18 healthy volunteers. Mean±SD basal TEWL was significantly higher in AD lesional/nonlesional skin at baseline (55.1 ± 5.5/28.0 ± 3.1 g × m−2 × h−1) than in healthy skin (14.0 ± 1.6) and decreased to 30.3 ± 3.1/22.0 ± 2.6 at week 16 and 29.7 ± 4.3/18.3 ± 2.1 at week 28; TEWL after 5/20 STS improved similarly. Baseline mean±SD TE in lesional/non-lesional skin (251.1 ± 25.8/166.1 ± 15.2 µm), significantly higher than in healthy skin (118.2 ± 5.1), decreased to 196.8 ± 18.4/141.9 ± 11.9 at week 16 and 160.4 ± 12.9/142.7 ± 15.6 at week 28. At weeks 16 and 28, there was no significant difference between TEWL or TE in AD lesional and nonlesional skin vs healthy skin.
Conclusion
Using non-invasive techniques to monitor epithelial function, dupilumab treatment restored skin barrier function in children with AD. Improvements achieved at week 16 were sustained to week 28
Complex mechanical loading and pro‐inflammatory cytokines in intervertebral disc degeneration
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Intervertebral disc (IVD) degeneration is a major contributor to low back pain, yet its initiating factors remain unclear. While the individual effects of pro-inflammatory cytokines and mechanical loading on IVDs have been studied, their combined impact is poorly understood. This study investigated how dynamic compression and torsion interact with interleukin-1 beta (IL-1β) and its inhibitor, interleukin-1 receptor antagonist (IL-1Ra), using bovine IVDs in an ex vivo organ culture system.
Methods
Whole bovine caudal IVDs were cultured for one week in a custom bioreactor applying diurnal dynamic compression (0.1–0.5 MPa) and torsion (±6°) under three media conditions: physiological, catabolic (10 ng/mL IL-1β), and inhibitory (10 ng/mL IL-1Ra). Static compression (0.1 MPa) served as control. 3 T magnetic resonance imaging (MRI) was used pre- and post-culture for imaging and segmentation using 3DSlicer. Subject-personalized finite element (FE) models were generated via morphing algorithms and coupled with a parallel network (PN) model to analyze metabolite transport and its impact on gene expression. Outcomes included disc height, glycosaminoglycan (GAG) content, qPCR, and cell metabolic activity.
Results & Conclusions
Degenerative changes were detected in all treatment groups. Results of decreased disc height, hydration, and ACAN expression, alongside increased MMP-13, indicated that the applied loading was supraphysiological and induced catabolic responses. IL-1Ra, at the given dose, did not counteract degeneration. MRI-based FE modeling effectively captured patterns of tissue consolidation and degeneration, providing valuable insights into IVD responses under combined mechanical and inflammatory stress. This integrative platform highlights the importance of modeling complex IVD environments and may inform the design of improved anti-catabolic therapies
Unusual biota and palynofacies of a Lower Devonian intermontane basin saline lake–playa mudflat ecosystem
Get PDFThe Strathpeffer–Struie Lower Devonian LORS (Lower Old Red Sandstone) deposits of the Northern Highlands of Scotland contain the decidedly unusual ‘foetid beds’. These are interpreted as being deposited in a highly saline sulphate lake and associated playa mudflat, which developed in an intermontane basin in the Caledonian Mountains of Laurussia. Palynological analysis was undertaken to investigate the biota and environments of deposition of these deposits. The sediments of the saline lake and associated playa mudflat reveal highly unusual palynofacies dominated by cyanobacterial, fungal and algal remains. Presumably the high salinity lacustrine conditions excluded grazing invertebrates and fish, enabling microbial mats and stromatolites to flourish, as is the case in modern high-altitude highly saline sulphate lakes. Dispersed spore assemblages recovered from the sequence are equated to the D–E Spore Assemblage Biozone/AP Oppel Zone (Pro Interval Zone) and suggest a latest Emsian age. The spore assemblages are depauperate compared with those from coeval lowland deposits from Laurussia, suggesting that the vegetation represents a restricted, partially endemic, upland flora. In the palynological samples, rare examples of the terrestrial fauna of the basin are represented by dispersed arthropod cuticle, including the earliest example of a scorpion pectinal tooth with peg sensilla
Making trials more inclusive of people experiencing socioeconomic disadvantage: developing the INCLUDE socioeconomic disadvantage framework
Get PDFBackground
People experiencing socioeconomic disadvantage are persistently underrepresented in clinical trials, yet they experience a significantly greater burden of disease than those not experiencing socioeconomic disadvantage. Trials need to be inclusive to ensure that treatments are safe and effective for those who need them most. Resources are needed to support researchers in designing and implementing trials that are inclusive of people experiencing socioeconomic disadvantage. Building on the National Institute for Health and Care Research (NIHR) INCLUDE initiative, we developed the INCLUDE Socioeconomic Disadvantage Framework to support researchers in making trials more inclusive.
Methods
The Framework was developed over five phases: (1) outlining an initial draft of the Framework, (2) refining the initial draft Framework with public contributors, (3) refining the draft Framework with wider contributors, (4) finalising the Framework with all contributors, and (5) launch and application of the Framework.
Results
The Framework entails four key questions: (1) Who should my trial results apply to? (2) Are people from different socioeconomic backgrounds likely to respond to the intervention in different ways? (3) Will my trial intervention and/or comparator make it harder for people from different socioeconomic backgrounds to take part in the trial? (4) Will the way I have planned and designed my trial make it harder for people from different socioeconomic backgrounds to take part? The Framework includes worksheets to support trial teams in considering strategies to address barriers to inclusion. In 2023, the Framework was launched at a webinar with ~300 registrants and is currently available to download from the Trial Forge website: https://www.trialforge.org/trial-diversity/socioeconomic-disadvantage-framework/. Public contributor considerations, collated through project meetings, to make trials more inclusive for people experiencing socioeconomic disadvantage are also appendaged to this article to support trial teams further.
Conclusion
The Framework and public contributor considerations can be used to support researchers to design and conduct more inclusive trials. Future work should include evaluation of such Frameworks, further engagement with funders to increase uptake, and development and evaluation of strategies to improve inclusion
PQDAST: Depth-aware arbitrary style transfer for games via perceptual quality-guided distillation
Get PDFArtistic style transfer is concerned with the generation of imagery that combines the content of an image with the style of an artwork. In the realm of computer games, most work has focused on post-processing video frames. Some recent work has integrated style transfer into the game pipeline, but it is limited to single styles. Integrating an arbitrary style transfer method into the game pipeline is challenging due to the memory and speed requirements of games. We present PQDAST, the first solution to address this. We use a perceptual quality guided knowledge distillation framework and train a compressed model using the FLIP evaluator, which substantially reduces both memory usage and processing time with limited impact on stylisation quality. For better preservation of depth and fine details, we utilise a synthetic dataset with depth and temporal considerations during training. The developed model is injected into the rendering pipeline to further enforce temporal stability and avoid diminishing post-process effects. Quantitative and qualitative experiments demonstrate that our approach achieves superior performance in temporal consistency, with comparable style transfer quality, to state-of-the-art image, video and in-game methods
KG-Retailbot: A knowledge graph-based chatbot for explaining robotic scenario information in a retail setting
Get PDFRobots are now pervasive, leveraging their automation capabilities to assist humans across a diverse range of tasks. Nevertheless, end-users may have a limited understanding of the robot’s operation and typically assume a passive role when interacting with the robot performing a particular task. In this study, we address the critical need for effective explainability in human-robot interaction. By comparing different methods of explaining robotic scenario information to end-users, the proposed methodologies use a labelled property graph-based chatbot that adheres to the IEEE Robotics Ontology Standards. In this study, we designed two virtual robotic scenarios and simulated their information flow using the Robot Operating System. A between-subjects experiment was conducted where participants engaged with the system through various interaction methods to understand the two scenarios. These methods included real-time Linux Command Line Interface outputs, querying a chatbot, exploring knowledge graphs, or a combination of chatbot and knowledge graphs. The study findings suggest that both the knowledge graphs and the chatbot significantly enhance the system’s explainability compared to a simple Linux terminal information output. Moreover, utilizing knowledge graphs alongside the chatbot has received better subjective evaluations concerning metrics such as clarity, usability, and robustness. This research made contributions towards the development of standardised labelled property graphs for representing scenario information in language-based human-robot interaction. The experiment design and evaluations also provided a solution for assessing the explainability of task-oriented dialogue systems both subjectively and objectively
Does music support executive functions and affective responses during acute exercise?:A systematic review and meta-analysis
Get PDFINTRODUCTION: Maintaining a steady running pace despite physical or mental fatigue often engages executive functions. These functions may contribute to sustaining exercise participation by regulating cognitive and affective responses to the demands of physical exercise. Research on both music and acute exercise independently shows engagement of executive functions and affective responses, with exercise intensities influencing outcomes. However, the combined effects of music and acute exercise on executive functions and affective outcomes remain underexplored. METHODS: Accordingly, this review examines how music may interact with executive functions and affective responses during acute exercise. RESULTS: Ten studies met the inclusion criteria, with nine providing data for effect size calculations across 21 intervention arms. Narrative synthesis indicated context-dependent patterns between music and acute exercise combinations, particularly at low-to-moderate exercise intensities. Meta-analyses report non-significant effects of music and acute exercise on attention allocation, inhibitory control, and core affect. A meta-regression pooling 18 effect sizes from nine studies suggested that higher exercise intensities and older mean participant age were associated with smaller effects of music and explained a substantial proportion of between-study variance, although residual heterogeneity remained high and these findings should be interpreted cautiously. A descriptive subgroup analysis showed a decreasing pattern across exercise intensities (low: g = 3.99; moderate: g = 0.99; high: g = 0.28), though substantial heterogeneity persisted, and the reported effects do not appear to generalize consistently across studies. DISCUSSION: The current synthesised evidence appears inconclusive regarding music's influence on executive functions and affective responses during acute exercise. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023465958
“The old world of words gives way to the world of code”:Literature and the Alt-Right in Hari Kunzru’s Red Pill
Get PDFIn an era defined by the digital escalation of right-wing xenophobia and intolerance, what political or ethical force, if any, can literature exert? My article addresses this question through a sustained analysis of Hari Kunzru’s novel Red Pill (2020). It examines the unnamed author– protagonist’s descent into paranoia and, eventually, psychosis. This mental health nosedive occurs when the British-Indian narrator’s liberal worldview is confronted by a charismatic alt-right media producer who normalizes nihilistic violence, dressing it up with literary references. Taking a cue from the parallels Kunzru draws between Weimar-era bigotry, the Stasi’s panoptic surveillance, and today’s digital ‘attention economy’ (Goldhaber, Crawford), I argue that Red Pill brings into sharp relief the failure of liberal tolerance in the face of slippery right-wing memes and apparently ironic agitprop. By staging the protagonist’s confrontation with the coded, racialized language of the alt-right, the novel interrogates new forms of political precarity and social divisions. It ultimately positions Kunzru’s brand of radical listening as a necessary, if dangerous, postcolonial intervention into the mirror worlds of contemporary society
What are paid care workers in England’s attitudes and considerations regarding organising?
Get PDFIn England, pay and working conditions in adult social care (ASC) employment are among the worst in the labour market. There are signs of positive reform through legislation being introduced by the Labour government elected in July 2024, but there are several obstacles to delivering meaningful change. With positive state-level policy slow to materialise, this article examines a dimension of paid care workers’ own efforts to bring about change, namely, their orientations towards organising. Levels of unionisation are comparatively low in ASC, and although effective union and non-union campaigns take place, the overall numbers and impact are limited. For organisations seeking to represent paid care workers to engage with them effectively, it is important to understand these workers’ views on organising for change. This article draws on an analysis of 45 interviews with paid care workers and key actors from organisations representing their interests, including unions and campaign groups. It presents findings regarding the dimensions of paid care work’s relational labour process and status. The analysis engages with scholarship on paid care workers’ wider work orientations and with the burgeoning literature on organising among paid care and domestic workers. By bringing together insights on paid ASC workers’ work orientations and their organising orientations in a novel way, it shows how paid care workers’ attachments to their relational work significantly shape orientations towards organising
Multimorbidity between Type 2 Diabetes and Depressive Symptoms in Mexico:Prevalence and Associated Factors From the Nationally Representative ENSANUT 2022 Survey
Get PDFAIMS: Type 2 Diabetes Mellitus (T2DM) and depression are major public health challenges, with Mexico ranking among the countries with the highest prevalence of both. Research into the bidirectional relationship between the two conditions in Mexico is scarse. This study aims to investigate the prevalence of T2DM and depression, the co-occurrence of these conditions, the strength of their association, and socio-demographic, and geographical factors contributing to their prevalence in Mexico. METHODS: We used data from the 2022 National Health and Nutrition Survey. T2DM was self-report. Depression was assessed using the Center for Epidemiological Studies Depression Scale. Descriptive statistics and multivariate logistic regression models were used to explore the bidirectional relationship and associated factors. RESULTS: A high prevalence of depressive symptoms (16.7%) and Type 2 Diabetes Mellitus (T2DM, 10.9%) was found in a representative sample for the Mexican population (n =11 913). Participants with T2DM had higher odds of depressive symptoms (OR:1.78, 95 95% CI: 1.48-2.14), and those with depressive symptoms were also more likely to have T2DM (OR:1.97, 95% CI:1.52-2.54) for ages 20-59, and for ages 60+ (OR: 1.63, 95% CI: 1.27-2.09). Women were more likely to report depression than men (OR:2.14, 95% CI:1.83-2.51), and older adults (60+) had over three times higher odds of depression compared to younger adults (OR:3.53, 95% CI:3.00-4.15). Higher education was protective against both conditions, with individuals having high school or higher education showing lower odds of depression (OR:0.41, 95% CI: 0.31-0.53) and T2DM (OR: 0.52, 95% CI: 0.37-0.74). CONCLUSIONS: Integrated strategies to address the co-occurrence of T2DM and depression are needed, particularly among vulnerable and older populations
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