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ColaCare: Enhancing Electronic Health Record Modeling through Large Language Model-Driven Multi-Agent Collaboration
Get PDFRegulatory T cell depletion promotes myeloid cell activation and glioblastoma response to anti-PD1 and tumor-targeting antibodies
Get PDFGlioblastoma is invariably lethal and responds poorly to immune checkpoint blockade. Here, we examined the impact of regulatory T (Treg) cell depletion on glioblastoma progression and immunotherapy responsiveness. In human glioblastoma, elevated Treg cell signatures correlated with poorer survival outcomes, with these cells expressing high levels of CD25. In Nf1-/-Pten-/-EGFRvIII+ glioblastoma-bearing mice, a single dose of non-interleukin-2 (IL-2) blocking (NIB) anti-CD25 (anti-CD25NIB) antibody depleted Treg cells and promoted CD8+ T cell clonal expansion and partial tumor control, further enhanced by programmed cell death-1 (PD1)-blockade. Treg cell depletion induced interferon-γ (IFN-γ)-dependent tumor microenvironment remodeling, increasing Fcγ receptor (FcγR) expression on intratumoral myeloid cells and enhancing phagocytosis. Combination of anti-CD25NIB with anti-EGFRvIII tumor-targeting antibodies resulted in complete tumor control. Anti-human CD25NIB treatment of glioblastoma patient-derived tumor fragments effectively depleted Treg cells and activated CD8+ T cells. These findings underscore the therapeutic relevance of Treg targeting in glioblastoma and unveil potent combination strategies for anti-CD25NIB based on innate cell activation.</p
Make, buy, and ally:Can plural sourcing reconcile the tension between outsourcing and corporate social responsibility?
Get PDFOutsourcing promises economic benefits but creates corporate social responsibility (CSR) risks: as activities are placed beyond a firm's boundaries, the firm struggles to adequately measure the performance of its suppliers, particularly regarding their environmental and social compliance. This study investigates how a buying firm's sourcing strategy can reduce CSR-related agency risks in outsourcing. This research uses an agency theory framework to argue that a buying firm's actual manufacturing experience as part of plural sourcing (i.e., the simultaneous pursuit of distinct governance forms such as make and buy, make and ally, or make, buy, and ally) can help it build CSR-specific supplier evaluation capabilities and thereby overcome agency-related performance measurement difficulties. To test the hypotheses, the authors consolidate a panel data set of 9057 firm-year observations based on US publicly traded manufacturing firms. The results confirm that plural sourcing is indeed effective in mitigating the negative impact of outsourcing on a firm's CSR performance but is contingent on two boundary conditions: the specific business segment (primary vs. secondary) where plural sourcing takes place and the buying firm's presence (i.e., whether the firm owns facilities) in the sourcing countries. With this, the study challenges the consensus in the literature that outsourcing-related CSR risks can be addressed solely through the governance of external supplier relations. In fact, firm-internal practices and the sourcing strategy of the buying firm can help to mitigate CSR risks in outsourcing relationships as well.</p
Financial incentives for smoking cessation among (expectant) parents:a systematic review of facilitators and barriers to implementation
No full textOBJECTIVE: Financial incentives, provided following validated smoking cessation, hold substantial potential to cost-effectively promote cessation. To facilitate wider adoption, we systematically reviewed evidence addressing the barriers and facilitators to successful implementation of incentive-based smoking cessation interventions among (expectant) parents.DATA SOURCES: We conducted a systematic search to identify scientific and grey literature across nine electronic databases, from inception to 15 August 2024. Search terms included combinations of "smoking cessation", "incentive", "pregnancy", "preconception" and "parent".STUDY SELECTION: Eligible records reported and reflected on the implementation of smoking cessation programmes with incentives for (expectant) parents. Inclusion criteria were applied by two reviewers independently, with discrepancies resolved through consensus. Of 1100 unique records identified, 37 met inclusion criteria.DATA EXTRACTION: Characteristics of the studies, interventions, incentives and implementation, along with barriers and facilitators, were independently extracted by two reviewers. Thematic analysis identified barriers and facilitators. Subgroup analysis explored patterns specific to lower socioeconomic populations.DATA SYNTHESIS: Studies reported on implementation in the USA (n=18), UK (n=10), Australia (n=4), the Netherlands (n=2), New Zealand (n=1), France (n=1) and international contexts (n=1). Barriers included misalignment with participants' context and resources, recruitment and retention challenges, limited reliability of abstinence verification and high resource demands. Facilitators included ensuring acceptability, accessibility, feasibility, funding and integration into health services.CONCLUSIONS: With the cost-effectiveness of financial incentives for smoking cessation among (expectant) parents already well-documented, this first systematic synthesis of the barriers and facilitators to implementing them in daily practice offers valuable guidance for advancing implementation efforts.PROSPERO REGISTRATION NUMBER: 2023:CRD42023407648.</p
Exploring outcome-driven policymaking on protected areas with an endogenous institutional model
No full textCovering over 16 % of the global land surface, nearly 300,000 Protected Areas (PAs) play a pivotal role in conservation efforts worldwide. The allocation and management of these areas vary widely, reflecting the dynamism and complexity of the land use system. Understanding the impacts of PA-related policy mixes on ecosystem service outcomes and the wider land system is essential but challenging. In this research, we employ an endogenous institutional model coupled with an agent-based land use model to examine the processes and feedbacks from PA implementation and land system changes under multiple policies. We focus on modelled PA policy targets that aim to reach conservation outcomes by increasing a proxy for habitat diversity. Alongside other policies with different targets in the land system, PA policies generate dynamic patterns that are challenging to discern through an exogenous, non-systemic lens. Findings reveal that 1) Neither subsidies nor PAs in isolation effectively enhance habitat diversity in the model; however, their synergic implementation effectively increases it. 2) Increasing PA extent to 30 % of the land area does not harm modelled agricultural output in the long term, due to the land system's resilience and adaptability in providing ecosystem services. 3) When the geographic extent of PAs is predetermined, radical expansion proves more beneficial than gradual expansion, as the latter causes prolonged disruptions to existing land uses while accruing fewer cumulative sustainability benefits over time. These insights highlight the importance of a systemic, integrated approach to PA management for sustainable conservation outcomes.</p
Crisis, transformation and learning:Perspectives on the future of learning in higher education
No full textThis paper discusses two learning concepts (problem-based learning,research-based learning) as promising approaches for initiating deep and sustainable learning processes. Drawing on Dewey and others, we use the notion of crisis and uncertainty as lenses to help locate ways of conceptualizing the beginning of learning. We present empirical findings from two research projects that were influenced by the concepts of crisis, uncertainty and learning. We close with a critical discussion of implications for the future of learning and the role of teachers in higher education
The Detection and Attribution Model Intercomparison Project (DAMIP v2.0) contribution to CMIP7
No full textThe first version of the Detection and Attribution Model Intercomparison Project (DAMIP v1.0) coordinated key simulations exploring the role of individual forcings in past, current and future climate as part of the Coupled Model Intercomparison Project, Phase 6 (CMIP6). The simulations have been used extensively in the literature for detection and attribution of long-term changes, constraining projections of climate change, attributing extreme events and understanding drivers of past and future simulated climate changes. Attribution studies using DAMIP v1.0 simulations underpinned prominent assessments of human-induced warming in the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report. Here, we describe the set of DAMIP v2.0 simulations, proposed for the next phase of CMIP, CMIP7. Detection and attribution studies rely on pre-industrial control simulations and historical simulations, which will be part of the Diagnostic, Evaluation and Characterization of Klima (DECK) set of simulations for CMIP7. In addition, we identify the three highest-priority single-forcing experiments for CMIP7 to be run as “Assessment Fast Track” simulations in support of the Seventh Assessment Report of the IPCC: simulations with natural forcings only, anthropogenic well-mixed greenhouse gases only and anthropogenic aerosols only. Beyond this, the DAMIP v2.0 experimental design includes full-column ozone-only simulations and land-use-only simulations, such that the set of individual forcing experiments, when these are considered together, represents the full set of historical forcings. While concentration-driven simulations are prioritised for attribution, emissions-driven versions of the DAMIP experiments are also proposed to support understanding of the influence of carbon-cycle feedbacks on the simulated responses to individual forcings
The relationship between dimensionality and duration of household poverty during childhood and onset of youth offending
No full textConcern about rising youth offending amidst a cost-of-living crisis in the UK has reignited policy and academic debates about the relationship between childhood poverty and youth offending. International research findings are mixed, however, possibly due to the variety of poverty measures analysed or inconsistent examination of duration of poverty exposure. This study sheds new light on the issue by assessing the potential association between four measures of household poverty – experienced persistently or intermittently – and youth offending, using a birth cohort study from Scotland. Findings show that persistent exposure to financial strain is the only form of poverty predictive of offending by age 12. The paper highlights an overlooked perspective on the poverty-offending nexus, with important implications for policy and research
Jugular Foramen Syndrome: Concurrent Neurological Deficits, Advanced Imaging Findings, Underlying Diagnoses, and Outcomes in 14 Dogs (2016–2024)
No full textBackground: Jugular foramen syndrome (JFS), dysfunction of cranial nerves (CNs) IX, X, and XI caused by lesions involving the jugular foramen (JF), is rarely reported in dogs.Objective: Describe presenting complaints, neurologic findings, advanced imaging findings, underlying diagnoses, and outcomes in dogs with JFS.Animals: Fourteen client-owned dogs.Methods: Retrospective, multicenter study of dogs diagnosed with JFS using advanced imaging between 2016 and 2024.Results: Affected dogs were older (median age, 9.9years; range, 7.9–14.5 years) and presented with chronic progressive clinical signs (median duration, 135days; range, 5–720days). Common presenting complaints included coughing (7/14), retching (6/14), head tilt (5/14), and laryngeal stridor (4/14). Neurologic abnormalities were noted in 11/14 dogs, with CN deficits (10/11), including unilateral laryngeal paralysis (5/10) and tongue atrophy (4/10), being the most common finding. Additional signs included head tilt (7/11) and postural reaction deficits (5/11). Intracranial lesions were identified in 10/14 dogs, with meningioma being the most frequent radiologic or histopathologic diagnosis. In dogs with extracranial lesions (4/14), thyroid carcinoma was common. Median survival time was 218days (range, 16–477days).Conclusion and Clinical Importance: Neoplastic or suspected neoplastic causes of JFS are common and lesions often extend beyond the JF by the time of diagnosis. As such, neurologic deficits in dogs with JFS often reflect involvement of multiple CNs, not limited to CNs IX, X, and XI. Advanced imaging of the head should be considered in dogs with clinical signs consistent with JF
Intimate polarisation:Political divisions within everyday family relationships in Colombia
Get PDFPolitical polarisation became a dominant concern in Colombia following the 2016 referendum in which a peace accord signed with the FARC guerrillas was rejected, and subsequent electoral processes in which the referendum identity divides were recycled and evolved. This article explores lived experiences of political divisions within intimate relationships in Colombia, and proposes an anthropological approach to complement the political science-dominated field of polarisation studies. It uses ethnographic storytelling to reveal how political divisions are enmeshed in myriad intersecting divides, including class, race, experiences of armed conflict and interpersonal histories, and draws on the anthropology of politics, ethnographies of the Colombian conflict and feminist scholarship to propose the concept of ‘intimate polarisation’: a political division felt, perceived or otherwise experienced within intimate, everyday relationships. This approach complicates the binary and normative assumptions inherent in the concept of ‘polarisation’ and invites a rethinking of the category and its political effects
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