Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma adenocarcinoma

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study. We prospectively validate the survival association of a clonal expression biomarker, Outcome Risk Associated Clonal Lung Expression (ORACLE), in combination with clinicopathological risk factors, and in stage I disease. We expand our mechanistic understanding, discovering that clonal transcriptional signals are detectable before tissue invasion, act as a molecular fingerprint for lethal metastatic clones and predict chemotherapy sensitivity. Lastly, we find that ORACLE summarizes the prognostic information encoded by genetic evolutionary measures, including chromosomal instability, as a concise 23-transcript assay

Service delivery and the role of clinical pharmacists in UK primary care for older people, including people with dementia: a scoping review

OBJECTIVE: As populations age globally, there is increasing prevalence of multiple long-term conditions, such as dementia, leading to many challenges. The burden on health and care services, economic pressures, and the necessity for innovative policies to better support older people and people with dementia becomes paramount. This review explores how clinical pharmacists working in UK primary care support older people and people with dementia. DESIGN: Scoping review. METHOD: This review was conducted following the framework for scoping reviews in accordance with the Joanna Briggs Institute (JBI) methodology. The search of Scopus, EMBASE, CINAHL, Web of Science, PsycINFO, and Cochrane was initially conducted in September 2022, and updated in August 2024. Searches included literature exploring the landscape of clinical pharmacy services for older people in the UK, focusing on roles and services delivered, perceptions, and experiences. RESULTS: A total of 30 articles were included. These detail the multifaceted responsibilities of clinical pharmacists in primary care for older people. Stakeholder perspectives, including healthcare professionals and patients, emphasised the positive outcomes of clinical pharmacist involvement, from reducing other practitioners' workloads to improving patient safety. However, communication gaps, concerns about competence from other healthcare professionals, and the need for clear role definitions emerged as challenges. Research focused on the experiences of underserved groups, such as people with dementia or from minority ethnic backgrounds, is lacking. CONCLUSIONS AND IMPLICATIONS: The review enhances our understanding of the primary care clinical pharmacist service in the UK and identifies gaps in evidence, emphasising the need for empirical studies on the experiences of older people with cognitive impairment and those from minority ethnic backgrounds. It provides insights into what makes an effective clinical pharmacist service, such as training and communication, which may help to inform international policy and practice and improve service provision globally

Can Danmu Enhance the Watching Experience for Chinese Viewers? An Audience Reception Study on Danmu Preference and Processing

Research into audiovisual translation (AVT) has grown significantly, yet the study of danmu, which comprises user-generated comments overlaid on audiovisual products, remains nascent. This study examines the reception of danmu, including both danmu commentary and danmu subtitling, among Chinese viewers on Bilibili through semi-structured interviews with 30 participants. A thematic analysis was performed to reveal the preferences and perceived effects of danmu on viewing comprehension, and viewer’s perspectives on the future mechanism of danmu. The finding shows that most participants valued danmu for enhancing video understanding, especially through its interactive and real-time commentary but suggested improvements to its display and filtering features for better comprehension. While viewers appreciated danmu’s creative and collaborative nature, they were cautious about standardising it or integrating it into Western platforms, citing concerns over linguistic barriers and potential disruption of the viewing experience. This study offers practical suggestions for improving danmu on platforms like Bilibili, advocating for a balance between amateur presentation and standardisation to ensure co-viewing experiences and image clarity. It also provides a foundational understanding of danmu reception and encourages further research to explore its acceptance on other over-the-top (OTT) platforms, such as Netflix, for potential global adoption

Advances in colon-targeted drug technologies

PURPOSE OF REVIEW: Herein, we present an overview of innovative oral technologies utilized in colonic drug delivery systems that have made significant translational and clinical advancements to treat inflammatory bowel disease (IBD) in recent years. RECENT FINDINGS: The colon is home to distinct physiological conditions, such as pH and microbiota, that have been exploited in the development of colonic drug delivery systems for the treatment of local and systemic diseases. However, given the intra and interindividual variability in the gastrointestinal tract of both healthy and diseased states, various systems have shown inconsistencies in targeted drug release to the colon. Recent breakthroughs have led to systems that incorporate multiple independent trigger mechanisms, ensuring drug release even if one mechanism fails due to physiological variability. Such advanced platforms have bolstered the development of oral biologics delivery, an especially promising direction given the lack of commercially available oral antibody medications for IBD. These concepts can be further enhanced by employing 3D printing which enables the personalisation of medicines. SUMMARY: Leveraging these novel technologies can accurately deliver therapeutics to the colon, allowing for treatments beyond gastrointestinal tract diseases. To realize the full potential of colonic drug delivery, it is paramount that research focuses on the clinical translatability and scalability of novel concepts

Static Output Feedback based Distributed Robust Model Predictive Control for Parallel Systems in Process Networks

The parallel system is a fundamental system architecture frequently encountered in process networks. A distributed robust model predictive control strategy is formulated for parallel systems with unmeasured states, utilizing a static output feedback framework. Parallel system architectures typically incorporate coupling as well as constraints and these distinguishing features are directly addressed by the controller design approach. A non-convex control problem results which is first solved by linear matrix inequalities (LMIs). Then, the input to state stability (ISS) of the resulting system is demonstrated. The effectiveness of the proposed approach is verified by both numerical simulation and experimentation

Disentangling the relationships between the SDGs and transportation

Transportation is a vital enabler of sustainable development, influencing economic, social, and environmental dimensions. In this research, we discuss and explore the intricate connections between transportation and the UN’s Sustainable Development Goals (SDGs), identifying the interconnection between the transportation sector and SDGs. Our investigation highlights the vast role of transportation within the SDGs’ scope, which was earlier limited to a few indicators; we stress transportation’s transformative potential, including its role in enhancing urban accessibility, reducing greenhouse gas emissions, promoting equity and inclusion, and fostering economic opportunities. Key findings underscore gaps in the current SDG framework, such as limited recognition of active mobility, inequities in access, and underrepresentation of transportation’s environmental and social impacts. In addition, thresholds for the different indicators interacting with the transport sector must be defined for a universal, transparent evaluation process. Moreover, there is a need to consider the interlinkage between several indicators within different goals that are closely linked, and their relationship should be considered when evaluated, and they should be evaluated simultaneously and not separately. The paper proposes refining indicators to capture the nuanced relationships between transportation and sustainable development, emphasizing context-sensitive approaches to address regional disparities and informal transit systems. By integrating transportation comprehensively within SDG planning and monitoring, policymakers can unlock its systemic benefits, accelerating progress toward the 2030 Agenda and fostering equitable, sustainable communities

Ambivalent Affective Labour, Datafication of Qing and Danmei Writers in the Cultural Industry

Danmei 耽美 culture, which features male-male romance and/or erotica, emerged in mainland China in the late 1990s and has been flourishing since the 2010s across East and Southeast Asia. The dynamic Chinese danmei culture has received significant attention in academia in recent years, either by mapping out the resistant potential against the heteronormativity or by highlighting the escapist route for expressing the women participants’ desires. The danmei culture has evolved into a transmedia landscape, and at the same time, an ever-expanding cultural industry being exploited by the logic of capital. Danmei writers as affective labors living in such a cultural industry have been rarely considered in present danmei studies. Through exploring the datafication of qing (情, affects and desires) via in-depth interviews with contracted danmei writers on Jinjiang, I examine the distinct feature of danmei writers as ambivalent affective labor. For danmei writers, the datafication and monetization of qing leads to increasingly formulaic writing. By selecting, appropriating and combing the elements in the database of qing, danmei writers are able to swiftly generate a male homoerotic love story that efficiently and effectively invoke the affects and desires of readers for better monetization. Pleasures and pains are both involved in doing the ambivalent affective labor, which further consolidates the precariousness of the affective labour. However, the affects and desires per se cannot be fully manipulated – transformative momentum is embedded in the water-like qing all the time

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network. Physical disability and cognition were assessed with the Expanded Disability Status Scale (EDSS) and the symbol digit modalities test (SDMT), respectively. SMRI, dMRI, and resting-state fMRI data were parcellated into 100 cortical and 14 subcortical regions to obtain networks of morphological covariance, structural connectivity, and functional connectivity. Connectivity matrices were merged in a multiplex, from which regional coreness-the probability of a node being part of the multiplex core-and coreness disruption index (κ)-the global weakening of the core-periphery structure-were computed. The associations of κ with disease status (PwMS vs. healthy controls), clinical phenotype, level of physical disability (EDSS ≥ 4 vs. EDSS < 4), and cognitive impairment (SDMT z-score < -1.5) were tested within a linear model framework. Using random forest permutation feature importance, we assessed the relative contribution of κ in the multiplex and single-layer domains, in addition to conventional MRI measures (brain and lesion volumes), in predicting disease status, physical disability, and cognitive impairment. We studied 1048 PwMS (695F, mean ± SD age: 43.3 ± 11.4 years) and 436 healthy controls (250F, mean ± SD age: 38.3 ± 11.8 years). PwMS showed significant disruption of the multiplex core-periphery organization (κ = -0.14, Hedges' g = 0.49, p < 0.001), correlating with clinical phenotype (F = 3.90, p = 0.009), EDSS (Hedges' g = 0.18, p = 0.01), and SDMT (Hedges' g = 0.30, p < 0.001). Multiplex κ was the only connectomic measure adding to conventional MRI in predicting disease status and cognitive impairment, while physical disability also depended on single-layer contributions. In conclusion, we show that multilayer networks represent a biologically and clinically meaningful framework to model multimodal MRI data, with disruption of the core-periphery structure emerging as a potential connectomic biomarker for disease severity and cognitive impairment in PwMS

Travel sustainability of new build housing in the London region: Can London's Green Belt be developed sustainably?

Although London's high-density compact city planning has largely delivered sustainable development in the urban core, the wider regional challenge is that housing targets have been consistently missed for the last decade, and the lack of supply is exacerbating the housing affordability crisis. Releasing Green Belt land has been cited as a solution. This paper analyses new build development in the London region from 2011 to 2022, and confirms that Green Belt policy needs reform – local authorities in the Green Belt have the lowest housing delivery in the region, and car dependent ‘leap-frog’ development is occurring beyond the Green Belt boundary. The relaxation of Green Belt restrictions could greatly boost development, but would also risk producing car dependent housing. This research produces a new Travel Sustainability Index using census travel behaviour data, and analyses the travel patterns of residents in new build housing over the last decade. The conclusions are that more sustainable Green Belt development can be achieved by prioritising development in Outer London and through extending existing towns and cities in the Greater South East. Achieving this outcome will require improved regional planning coordination and infrastructure investment