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On canonical differential equations for Calabi-Yau multi-scale Feynman integrals
No full textWe generalise a method recently introduced in the literature, that derives canonical differential equations, to multi-scale Feynman integrals with an underlying Calabi-Yau geometry. We start by recomputing a canonical form for the sunrise integral with all unequal masses. Additionally, we compute for the first time a canonical form for the three-loop banana integral with two unequal masses and for a four-loop banana integral with two unequal masses. For the integrals we compute, we find an ϵ-form whose connection has at most simple poles. We motivate our construction by studying the Picard-Fuchs operators acting on the integrals considered. In the appendices, we give a constructive explanation for why our generalisation works
Building beyond profit: the history and potential future of non-profit construction companies
No full textWhen housing construction slows down due to diminished profit margins while the actual need for housing increases, people might raise the question: is residential construction best left to the capitalist market? What about introducing other ownership structures not dependent on sustained and rising profits? These are the same questions we raise in this paper, which examines Sweden’s long and prominent history of alternative ownership structures in the residential construction sector, including the rise and fall of public and large-scale union-owned construction companies in the twentieth century. After these vanished in the 1990s, the dominant approach to the recurrent problems in the sector has been limited to demand-side interventions and deregulation. This paper draws on the Swedish house building history to tackle the question of whether construction companies with alternative ownership structures and relationships to profit should – and could – be reintroduced into the sector
A [11C]PBR28 PET study on the associations between sleep health and microglial density
No full textSleep disturbances and inflammation are interconnected through shared regulatory mechanisms and are both implicated in age-related diseases. However, their connection at the level of brain-specific inflammation remains underexamined in humans. This study investigated whether specific dimensions of sleep are associated with microglial density, as measured by translocator protein (TSPO) levels, a biomarker of neuroinflammation. TSPO levels were measured using a single [11C]PBR28 positron emission tomography (PET) scan in 39 healthy adults aged 50-81 years (Mage = 66.7, SD = 8.9; 19 females, 20 males). Sleep dimensions were assessed using the Karolinska Sleep Questionnaire on three occasions over five years, twice before and once around the time of PET imaging. Shorter sleep, more frequent napping, daytime fatigue, and sleep insufficiency were associated with higher TSPO levels in the middle frontal cortex (MFC). Conversely, longer sleep was associated with higher TSPO levels in the hippocampus and putamen. Exploratory factor analysis and bootstrapping confirmed a negative association between a factor representing shorter sleep and MFC TSPO levels. Additionally, a greater deviation from optimal sleep duration over the five years, in either direction from eight hours, was associated with higher current TSPO levels in all but one examined brain regions. Peripheral C-reactive protein levels did not significantly correlate with the sleep variables or TSPO levels in any of the brain regions. Analyses were adjusted for age and sex. These findings suggest that insufficient and prolonged sleep durations are associated with elevated microglial density in frontostriatal and limbic systems, respectively, among healthy middle-aged and older adults, without any associations with peripheral inflammation. Further longitudinal studies are needed to clarify directionality and whether changes in sleep duration over time may serve as early indicators of brain health
Rationale and design of a registry-based randomized controlled study of personalized biomarker-based risk score-guided stroke prevention treatment in atrial fibrillation
No full textBackground: Stroke and reduced survival are devastating complications of atrial fibrillation (AF). Biomarker-based ABC-AF risk scores improve risk prediction in AF, and risk-guided treatment recommendations may improve patient outcomes. Design: The ABC-AF study is a national, multicenter, prospective, registry-based, randomized controlled, parallel-group, open-label study. Its primary objective is to evaluate whether ABC-AF risk score-guided treatment recommendations improve outcomes in patients with AF. Consenting patients with AF registered in the Swedish national quality register for AF, AURICULA AF, will be randomized in a 1:1 ratio to either ABC-AF risk score-guided treatment recommendations or standard care. For participants in the active arm, investigators will receive a visual presentation of stroke and bleeding risks along with recommendations regarding the choice of oral anticoagulant (OAC) and additional treatments for stroke and bleeding prevention. In the control arm, patients are managed at the discretion of the investigator. Outcomes: The primary outcome is a composite of stroke or death. Secondary outcomes include the composite of stroke, death, and major bleeding, and the individual components of the primary outcome, myocardial infarction, and hospitalization for heart failure; and a safety endpoint of major bleeding. Study enrollment commenced on October 25, 2018, and terminated on May 12, 2023, after 3,933 patients had been recruited. Study results are expected in 2025. Summary: The ABC-AF study evaluates whether a personalized treatment recommendation strategy-guided by the biomarker-based ABC-AF risk score decision support- improves outcomes in AF. (Am Heart J 2025;290:161-169.
Inflammatory imbalance and activation deficits in T cells of myasthenia gravis patients revealed by proteomic profiling
No full textMyasthenia gravis (MG) is a heterogeneous autoimmune disorder characterized by neuromuscular transmission failure and skeletal muscle fatigability, with a pathophysiology involving both cellular and humoral immune components. Despite growing interest in the immunological etiology of MG, few functional studies have addressed the role of T cells, and most existing work has focused on quantifying immune cell subsets using flow cytometry. In this study, a comparative in vitro analysis of resting and activated CD4+ and CD8+ T cells from MG patients and healthy controls (HC) was performed using the multiplex Proximity Extension Assay (PEA) proteomics to assess the secretion of inflammatory proteins, including cytokines and chemokines, and to define the inflammatory status of T cells in MG. Data analysis was performed using the Boruta algorithm to detect both linear and non-linear patterns, followed by multiple testing corrections, and correlation analyses. The results revealed distinct alterations in the secretion profiles of several inflammatory proteins in MG compared to HC across both T cell subsets, regardless of activation state. Notably, resting CD4+ T cells from MG patients secreted higher levels of VEGFA, TNFRSF9, TWEAK, CCL20, HGF, CCL19, TRAIL, IL18, and TNF-beta whereas resting CD8+ T cells secreted higher levels of IL-12B, TRAIL, CCL23, CD244, CXCL11, CCL20, VEGFA, PD-L1, and OSM relative to HC. In contrast, activated CD4+ and CD8+ cells from MG patients exhibited a blunted secretion profile compared to HC, suggesting functional exhaustion. Furthermore, MG-ADL scores correlated with the secretion levels of 14 proteins from resting CD4+ cells, including seven cytokines, five chemokines, and two matrix metalloproteins. Some of the CD4+ T cell secreted proteins also correlated with their corresponding serum or plasma levels in vivo. Overall, these findings indicate that T cells in MG exhibit a skewed inflammatory profile characterized by heightened basal activation and impaired inducibility, suggestive of an exhausted phenotype. The interplay between these altered T cell functions and aberrant B cell responses in MG warrants further investigation and may provide novel insights into disease immunopathophysiology as well as opportunities for targeted immunomodulatory therapies
Measuring respectful maternal and newborn care in Nepal : Comparing linked observation and interview data- prospective cohort study
No full textBackground Respectful maternal and newborn care is the cornerstone of high-quality care, however, measuring experience of respectful care has challenges since it can be subjective, and dependent on expectations. In this study, we assess the concordance between women’s reported experiences of respectful maternal and newborn care and independent observation of their care in Nepal. Methods This is a secondary analysis of a prospective cohort study among 22832 pregnant women conducted in three high volume hospitals in the country: Koshi Provincial Hospital (Hospital A), Bharatpur Hospital (Hospital B), and Lumbini Provincial Hospital (Hospital C) for 18 months between April 2017 and October 2018. The study implemented direct observation during and semi-structured interviews at discharge to evaluate the quality of maternal and newborn care in three large public hospitals. For this analysis, three domains for respectful maternal and newborn care were considered: 1) consent and counselling 2) respect and dignity of care, and 3) care provision. The two data sources (observation checklist and semi-structured interview) were plotted to these three domains to identify common indicators. The level of agreement (LOA) between two measurements was compared using Cohen kappa scores (κ) and Bland Altman plots. Findings During the study period, 22832 women had both observation and interview completed. For consent and counseling, 78.8% of women reported being informed about routine care while only 47.3% were observed to have been consented and counseled (k, LOA = 59.1%). For respect and dignity of care, 99.0% of women reported being treated with dignity and respect and 96.4% were observed (k, LOA = 95.4%). For care provision, 37.9% reported that the infant was kept in immediate skin-to-skin contact after delivery while only 3.9% were observed (k, LOA = 61.7%). Conclusion A significant difference existed between observed and self-reported measures of maternal and newborn care. This study highlights the need for a measurement approach that incorporates independent observations alongside self-reported data. There is also a need to further explore concordance between different sources for progress monitoring
Empowerment and quality of life in gynecological cancer survivors : Outcomes from a multicenter quasi-experimental cohort study from Norway (the LETSGO trial)
No full textBackground Increasing outpatient demands and unmet patient needs necessitate personalized follow-up care for cancer survivors. This study investigated whether a self-management-focused follow-up model improves empowerment and quality of life (QoL) in gynecological cancer survivors compared to standard follow-up.Methods Twelve Norwegian hospitals participated in this cohort study. Patients initiating routine follow-up after primary treatment were eligible and allocated to either intervention or standard care follow-up groups based on their treatment hospital. The intervention included nurse-led consultations using coaching techniques for education on symptom monitoring and healthy lifestyle, alternated with physician-led consultations and access to a mobile app. Standard follow-up consisted of physician-led consultations only. The primary outcome was change in patient empowerment over 12 months, measured with the self-monitoring and insight domain of the Health Education Impact Questionnaire (heiQ). Secondary outcomes included changes in remaining heiQ domains and QoL. Data were analyzed according to intention-to-treat principles using linear mixed effects models.Results Among 741 participants (intervention: 378, standard: 363), baseline characteristics were comparable. At 12 months, no significant differences were observed in self-monitoring and insight (Delta = 0.02 [95% confidence interval (CI), -0.04 to 0.08]; effect sizes [ES] = 0.29). However, health-directed activity (Delta = 0.15 [95% CI, 0.04-0.25]; ES = 0.15), emotional well-being (Delta = 0.12 [95% CI, 0.02-0.20]; ES = 0.15), social functioning (Delta = 5.2 [95% CI, 1.1-9.3]; ES = 0.41), and physical functioning (Delta = 2.5 [95% CI, 0.0-5.0]; ES = 0.20) were significantly more improved in the intervention group.Conclusion Lifestyle and Empowerment Techniques in Survivorship of Gynaecologic Oncology follow-up did not significantly impact self-monitoring and insight, but positively influenced other survivorship domains, indicating its potential for enhancing self-management and QoL in gynecological cancer survivors
Installation and Integration of Ultraviolet Photodissociation into the ScimaX MRMS system
No full textA Multicomponent aza-Prins Strategy for the Diastereoselective Synthesis of Piperidine-Fused Dihydroquinazolinones
No full textDihydroquinazolinones (DHQs) and piperidines are widely acknowledged as privileged structures and are of significant interest for the development of new drug candidates. Herein, a novel aza-Prins strategy is presented for the synthesis of piperidine-fused DHQs through a domino multicomponent reaction. Homoallylic ammonium halide salts are found to react with bifunctional aldehydes under acidic conditions to give halide-substituted fused piperidines in a diastereoselective fashion. The reaction can be extended to the incorporation of alcohol nucleophiles via fine tuning of the reaction conditions. Finally, the utility of the substituted compounds is demonstrated by performing a variety of functionalization reactions on the scaffold
Associations between Taq1A/C957T Polymorphic Variants and Autonomic Responsivity in a Slot Machine Task : Influence of real-life Gambling Exposure and Sex
No full textMonetary reward processing during gambling is associated with dopaminergic functioning. Emotional reactivity to different gambling stimuli can be indexed by autonomic nervous system (ANS) responses measured by skin conductance responses (SCR) and heart rate (HR). Genetic markers regulating neural dopaminergic activity, such as the D2 dopamine receptor, might confer differential sensitivity to gambling stimuli, which may also be modulated by previous exposure to gambling. To date, no previous studies have explored the relationship between genetic markers of the D2 dopamine receptor, real-life gambling exposure and ANS responses during gambling. Hence, this study explored associations and interactions between DRD2 C957T (rs6277) and ANKK1 Taq1A (rs1800497) genotypes, real-life gambling frequency and autonomic responses during reward anticipation and outcome delivery in a slot machine task producing wins, near-misses and full-misses. Participants (n = 270) performed a computerized slot machine task with recordings of SCRs and HR responses during gambling performance and provided saliva samples for DNA extraction. Taq1A A1 carriers showed increased SCRs and HR responses during reward anticipation and to wins. Greater responsivity during anticipation, as well as to wins and full-misses, was also observed in C957T heterozygotes. Regarding real-life gambling involvement, higher gambling frequency among Taq1A A1 carriers was associated with decreased HR responses during anticipation and to wins. Results suggest that polymorphic variants of the D2 dopamine receptor may confer differential sensitivity to different gambling stimuli which may further be modulated by real-life gambling exposures. However, further studies are needed in well powered samples of gamblers and control subjects