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Infinite-mean models in risk management: Discussions and recent advances
No full textIn statistical analysis, many classic results require the assumption that models have finite mean or variance, including the most standard versions of the laws of large numbers and the central limit theorems. Such an assumption may not be completely innocent, and it may not be appropriate for datasets with heavy tails (e.g., catastrophic losses), relevant to financial risk management. In this paper, we discuss the importance of infinite-mean models in economics, finance, and related fields, with recent results and examples. We emphasize that many results or intuitions that hold for finite-mean models turn out to fail or even flip for infinite-mean models. Due to the breakdown of standard thinking for infinite-mean models, we argue that if the possibility of using infinite-mean models cannot be excluded, great caution should be taken when applying classic methods that are usually designed for finite-mean cases in finance and insurance
Automated and Decentralized Genomic Profiling of Plasma Cell-Free DNA for Identification of Targetable and Resistance Alterations in Advanced Solid Tumors
No full textBACKGROUND: Existing circulating cell-free DNA (cfDNA) assays are primarily centralized, requiring specialized sample handling and transportation. Implementing a flexible, decentralized sequencing system at point of care, with minimal technical oversight, can enhance turnaround times and patient access to genomic profiling. In this study, we aimed to evaluate the clinical feasibility of an automated and decentralized cfDNA next-generation sequencing (NGS) assay for identifying actionable alterations in advanced solid tumors. METHODS: Genomic profiling of plasma cfDNA from 298 patients with advanced solid tumors was conducted using an automated NGS assay. We assessed concordance of tumor mutations detected in plasma cfDNA and patient-matched tumor tissues analyzed by an FDA-approved assay, investigating clinical factors influencing circulating tumor DNA (ctDNA) aberration (mut-ctDNA) detection sensitivity. RESULTS: Sequencing success rates for cfDNA genomic profiling was significantly higher than archived tumor tissue (99% vs 96%). Mut-ctDNA detection rates ranged from 20% to 67% across different solid tumors. Targetable or resistance alterations were found in 18% of the patients. About 72% of the patients showed concordant alterations from tissue and plasma. The level of concordance was associated with the cancer type, tumor burden, and metastatic location. Notably, 63 plasma-only alterations were identified in 18% of patients and were more frequently observed in those with prior targeted treatments (24%) compared to chemotherapy (10%). CONCLUSIONS: This study underscores the clinical feasibility of an automated, decentralized cfDNA genomic profiling approach. It emphasizes the importance of considering confounding clinical factors when selecting plasma- or tissue-based profiling assay. Such an approach holds promise for enhancing patient access to timely genomic profiling and targeted therapy selection
Evidence for Longitudinally Polarized W Bosons in the Electroweak Production of Same-Sign W Boson Pairs in Association with Two Jets in pp Collisions at √s = 13 TeV with the ATLAS Detector
No full textThis Letter reports the first evidence of electroweak production of same-sign W boson pairs where at least one of the W bosons is longitudinally polarized and the most stringent constraint to date for the production of two longitudinally polarized same-sign W bosons. The dataset used corresponds to an integrated luminosity of 140 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the ATLAS detector during run 2 of the Large Hadron Collider. The study is performed in final states including two same-sign leptons (electrons or muons), missing transverse momentum, and at least two jets with a large invariant mass and a large rapidity difference. Two independent fits are performed targeting the production of same-sign W bosons with at least one, or two longitudinally polarized W bosons. The observed (expected) significance of the production with at least one longitudinally polarized W boson is 3.3 (4.0) standard deviations. An observed (expected) 95% confidence level upper limit of 0.45 (0.70) fb is reported on the fiducial production cross section of two longitudinally polarized same-sign W bosons
Quantum-enhanced multiparameter sensing in a single mode
No full textPrecise measurements underpin scientific and technological advancements. Quantum mechanics provides an avenue to enhance precision, but it comes with a restriction: Incompatible observables, such as position and momentum, cannot be simultaneously measured to arbitrary accuracy as decreed by Heisenberg's uncertainty principle. This restriction can be bypassed by instead measuring commuting modular observables, which are counterparts to the naturally incompatible observables. Here, we measure modular observables to estimate small changes in position and momentum with a single-mode multiparameter sensor. We deterministically prepare grid states in the mechanical motion of a trapped ion and demonstrate uncertainties in position and momentum below the standard quantum limit (SQL). Further, we examine another pair of incompatible observables-number and phase. We prepare a different resource-number-phase states-and demonstrate a metrological gain over the SQL. These results introduce previously unidentified measurement capabilities unavailable to classical systems and mark a substantial step in quantum metrology
Experimental and analytical investigation of flexural behaviour of UHPFRC retrofitted bridge deck and barrier under vehicular impact
No full textThe steady increase in the weight of vehicles on the highway poses growing challenges to bridge safety. This article is concerned with strengthening the cantilevered deck slab adjacent to vehicular barriers by placing a membrane made of ultra-high performance fibre reinforced concrete (UHPFRC) for countering flexural demand at the fixed end of the cantilever caused by vehicular impact combined with gravitational loads. In this study, the overlay was found from impact tests to be highly effective in widely distributing an impact action transmitted from the point of contact on the barrier to the adjoining slab. The moment of resistance of the slab is also enhanced significantly by composite action between the overlay and the concrete substrate. Attributed to the dual enhancement mechanism, the overload ratio of the UHPFRC retrofitted cantilevered slab (defined herein as the flexural resistant capacity of a unit length of the slab divided by the demand of the combined action) is approximately double of that of the conventional concrete slab for the same impact scenario
A qualitative study of body image among competitive women pole dancers
No full textAn emerging literature suggests that recreational pole dancing promotes body confidence via a sense of belonging, body diversity, and free sexual expression. However, it's unclear whether these positive experiences extend to competitive pole contexts. Research among athletes suggests that competitive environments often promote rigid expectations of athletic bodies, body comparisons, and self-objectification. These body insecurities can persist beyond competition. The current study aims to address this gap by exploring how competitive pole dancing contributes to women's perceptions of their bodies in and out of competitive environments. Participants (N = 20 women) were recruited via emails and flyers disseminated across pole studios and event organizers in Australia to participate in semi-structured interviews. Using reflexive thematic analysis, we constructed three themes: (i) Body functionality is paramount; (ii) Community provides nurturance and tensions for belonging; (iii) Empowerment through autonomy. Although competitive environments provided opportunities for comparison and insecurities, prioritizing the ability to view and appreciate one's body primarily through a functional manner allowed women to achieve positive perceptions of their bodies in and out of competition. The findings provide a deeper understanding of the factors uniquely contributing to body image in a novel sample of pole dancers, offering strategies for training regimens and interventions that may benefit women's body image in competitive and social contexts
Systemic Biologics Have Similar Safety to Vedolizumab in Inflammatory Bowel Disease Patients Following Liver Transplantation
No full textBACKGROUND AND AIMS: 'Gut-specific' biologics are associated with fewer infectious complications than 'systemic' biologics in inflammatory bowel disease (IBD) which represents an important consideration in transplant recipients. This study evaluated the safety of combining transplant immunosuppression with 'gut-specific' versus 'systemic' biologics to manage IBD following liver transplantation (LTx). METHODS: A retrospective dual-centre study of IBD patients exposed to biologics following LTx between 2001 and 2023 was undertaken. Primary outcome was the incidence rate of infectious events per patient-year of biologic exposure. Infectious events were stratified by 'gut-specific' (vedolizumab) and 'systemic' (anti-TNF/ustekinumab) biologic exposure with severe events defined by hospitalisation. Secondary outcomes included the impact of non-biologic immunosuppression on the incidence of infectious and non-infectious complications. RESULTS: Thirty-six IBD patients were exposed to 59 (median 12 [IQR 6-27] months) biologic episodes following LTx. Patients were collectively exposed to 44.5 and 44.4 patient-years of 'gut-specific' (vedolizumab = 27 [45.7%]) and 'systemic' (anti-TNF = 22 [37.2%]; ustekinumab = 10 [16.9%]) biologics, respectively. Twenty-seven (45.7%) biologic episodes were associated with 41 infectious events, a median of 8 months (IQR 4.5-13.5) following biologic initiation. Rates of infectious events were not significantly different between 'gut-specific' and 'systemic' biologic exposures (0.43 vs. 0.50 per patient-year, incidence rate ratio [IRR] 1.09 [95% CI 0.58-2.02, p = 0.79]). Corticosteroid exposure at biologic initiation was the only non-biologic immunosuppressant associated with severe infectious events (IRR 5.40 [95% CI 1.66-17.63, p < 0.01]). CONCLUSION: Incidence of infectious events observed between IBD/LTx patients exposed to 'gut-specific' and 'systemic' biologics were similar. Biologic choice should not be influenced by concerns regarding their co-prescription with transplant immunosuppression. Corticosteroid co-therapy at biologic initiation may be associated with more severe infectious events
Hyperglycemia and kidney outcomes in critically ill children and young adults on continuous kidney replacement therapy
No full textBACKGROUND: There are limited studies evaluating hyperglycemia in children treated with continuous kidney replacement therapy (CKRT). We evaluated the association of hyperglycemia with kidney outcomes in critically ill children treated with CKRT for acute kidney injury (AKI) or fluid overload. METHODS: Secondary analysis of the multicenter retrospective observational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) study (34 centers, 9 countries). Primary exposure was hyperglycemia on days 0-7 of CKRT (average serum glucose of ≥ 150 mg/dL). Average serum glucose 125% baseline serum creatinine, or dialysis dependence]). RESULTS: Of 985 participants, 48% (473) had average serum glucose > 150 mg/dL during days 0-7 of CKRT. There were higher rates of death in the hyperglycemic group (44% vs. 32%, p < 0.001) and longer length of stay among survivors (42 vs. 38 days, p = 0.017) compared to the euglycemic group. Those with average glucose ≥ 150 mg/dL had higher unadjusted odds of MAKE-90 (OR: 1.36, 95% CI 1.02-1.81); this finding did not remain after multivariate adjustment. Those with average glucose ≥ 180 mg/dL had higher adjusted odds of MAKE-90 (aOR: 1.44, 95% CI 1.02-2.04). In adjusted analysis, each 10 mg/dL increase in glucose was associated with 3% increased odds of MAKE-90. CONCLUSIONS: Hyperglycemia is associated with worse kidney outcomes among young persons on CKRT for AKI or fluid overload. Further studies are needed to evaluate the causality and determine appropriate glucose ranges in this high-risk population
Examination of speech processing in noise reveals cognitive deficits in early Huntington's disease
No full textProcessing speech amongst noise requires sensory and cognitive abilities that are often affected by Huntington's Disease. However, their impact on daily communication remains unclear. We examined the effects of Huntington's Disease on speech-in-noise processing using everyday sentences and words in noise contexts and conditions that mimic different daily life scenarios. In Premanifest (n = 16) and Manifest Huntington's Disease (n = 12) and Control (n = 26) participants, we examined speech discrimination amongst non-demanding and attentionally demanding noise. We also examined how Huntington's Disease affected the ability to use spatial separation cues to disambiguate speech from noise in single-voice masker or multi-talker backgrounds. Finally, we administered a validated questionnaire where participants rated auditory processing difficulties during daily life activities. Sentence-in-noise discrimination was impaired in individuals with Manifest Huntington's Disease in almost all signal-to-noise ratio conditions with the attentionally-demanding masker and amongst the non-demanding noise masker with the most difficult signal-to-noise ratio. Premanifest Huntington's Disease participants had difficulty perceiving speech in some attentionally demanding noise conditions. Spatial cues provided situational benefits to speech processing under attentionally-demanding conditions for participants at all stages of Huntington's Disease, except for the Manifest Huntington's Disease group when stimuli included a single competing speaker. A logistic regression model using speech processing performance as a predictor successfully distinguished healthy control and Premanifest groups with 87.5% accuracy. Stage-dependent impairments in speech processing were observed under naturalistic noise conditions. These results further our understanding and contextualization of communication difficulties experienced by people with Huntington's Disease
Assessment of ventilation heterogeneity in severe asthma using phase-resolved functional lung magnetic resonance imaging
No full textVentilation heterogeneity is a hallmark of asthma. This study examines the feasibility of phase-resolved functional lung magnetic resonance imaging (PREFUL MRI) in the evaluation of ventilation heterogeneity in severe asthma, its response to bronchodilator, and correlation with spirometry. Twenty-three patients with severe asthma and seven healthy volunteers completed PREFUL MRI and spirometry pre and post-bronchodilator. Ventilation heterogeneity was assessed using ventilation defect percentages (VDP) for regional ventilation (RVent) and flow-volume loop cross-correlation (FVL), interquartile distance (IQD), and inhomogeneity index (IHI). Patients exhibited a significantly higher pre-bronchodilator VDPRVent (19.9 ± 14.0 vs. 1.9 ± 1.9%, p < 0.001), VDPFVL (21.6 ± 15.9 vs. 1.7 ± 2.1%, p < 0.001), IQD (0.60 ± 0.25 vs. 0.30 ± 0.06, p < 0.001), and IHI (0.34 ± 0.12 vs. 0.18 ± 0.04, p < 0.001) compared to healthy volunteers. Post-bronchodilator, VDPRVent (14.7 ± 12.5 vs. 19.9 ± 14.0%, p = 0.02), IQD (0.51 ± 0.20 vs. 0.60 ± 0.25, p = 0.02), and IHI (0.30 ± 0.11 vs. 0.34 ± 0.12, p = 0.02) decreased significantly in patients but remained significantly higher than in healthy volunteers. Significant correlations were observed between pre-bronchodilator FEV1 and VDPRVent (ρ = -0.61, p < 0.001), VDPFVL (ρ = -0.73, p < 0.001), IQD (ρ = -0.57, p = <0.001), and IHI (ρ = -0.60, p < 0.001). PREFUL MRI derived markers of ventilation heterogeneity are worse in patients with asthma, improve post-bronchodilator, and correlate with the severity of airflow obstruction. These findings support the role of PREFUL MRI in assessing ventilation heterogeneity in asthma