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White-box micro-adaptive query processing
No full textOperator performance in in-memory data management systems (DMS) often suffers from micro-architectural hazards such as cache misses and branch mispredictions. While many operators have alternative implementations that are robust against such hazards, these generally perform worse when no hazards are encountered. Unfortunately, hazards are caused by order-dependent data characteristics that query optimizers struggle to capture (e.g., sortedness, clusteredness) making a prior hazard-conscious optimization difficult. Additionally, statically optimized plans fail to adapt when data characteristics vary within a table. To address these problems, we propose a hazard-adaptive approach to query execution. Through hardware-assisted runtime profiling of low-level metrics, operators dynamically adapt to "hazardous" data. We propose an architecture for hazard-adaptive operators and integrate our approach into a DMS. We demonstrate that using hazard-adaptive operators provides a ~2-20× speedup across several TPC-H queries
Positioning imatinib for pulmonary arterial hypertension: a dose finding phase 2 study
No full textRationale: Imatinib, 400 mg daily, reduces pulmonary vascular resistance and improves exercise capacity in patients with pulmonary arterial hypertension. Concerns about safety and tolerability limit its use.
Objectives: We sought to identify a safe and tolerated dose of oral imatinib between 100 mg and 400 mg daily and evaluate its efficacy.
Methods: Oral imatinib was added to the background therapy of 17 patients with pulmonary arterial hypertension, including 13 who were implanted with devices that provide daily measurements of cardiopulmonary hemodynamics and physical activity. The first patient was started on 100 mg daily. The next 12 patients, recruited serially, were started on 200 mg, 300 mg, or 400 mg daily, following a continuous reassessment dose-finding model. An extension cohort (Patients 14–17) received 100 mg or 200 mg daily.
Measurements and Main Results: The continuous reassessment model recommended starting dose was 200 mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (−6.5 mm Hg; 95% confidence interval [CI] = −2.4 to −10.6; P < 0.01) and total pulmonary resistance (−2.8 Wood units; 95% CI = −1.5 to −4.2; P < 0.001), with no significant change in cardiac output. The reduction in total pulmonary resistance was dose and exposure dependent; the reduction from baseline with imatinib, at 200 mg daily, was −20.3% (95% CI = −14.3 to −26.3%). Total pulmonary resistance and night heart rate declined steadily over the first 28 days of treatment and remained below baseline up to 40 days after imatinib withdrawal.
Conclusions: Oral imatinib, 200 mg daily, is well tolerated as an add-on treatment for pulmonary arterial hypertension. A delay in the return of cardiopulmonary hemodynamics to baseline was observed after imatinib was stopped
The influence of national origin cues in HPV vaccination advertising: an eye-tracking study of visual attention and vaccine perception using quantitative and qualitative analysis
No full textThis study is among the first to investigate how national origin cues influence visual attention and perception in HPV vaccine advertisements, using eye-tracking technology to provide objective insights into consumer responses. By integrating methods from public health, psychology, and advertising research, this study explores how visual attention is shaped by national affiliation cues. In a controlled experimental setting with a sample of 40 UK university students, we investigated visual attention and effectiveness of HPV vaccination advertisements by comparing ads disclosing the national origin of the vaccine and without any origin information. We assessed total fixation duration and time to first fixation to various elements of the ad, along with intention and attitude measures. Contrary to one of our hypotheses, we did not find significant differences in intention (p = .758) and attitude (p = .620) measures. However, there was significant difference in total fixation duration toward one of the ad images between conditions (p = .043). The qualitative analysis reveals the role of country-of-origin (COO) in HPV vaccination advertising, suggesting a shift in attention from that image to the COO cue. Furthermore, eight out of the 20 participants in the treatment condition did not fixate at the COO cue. Findings provide critical insights for public health communication strategies, suggesting that the use (or omission) of national origin cues in vaccine advertisements could influence vaccine perception and hesitancy. These results highlight the need for strategic messaging approaches to enhance HPV vaccine acceptance and improve public trust in domestic and international vaccines
Construction of an organic cage-based porous ionic liquid using an aminal tying strategy
No full textAn aminal tying method was applied to post-synthetically modify a flexible organic cage, RCC1, to construct a porous ionic liquid (PIL). The resulting PIL, [RCC1-IM][NTf2]6, displayed melting behaviour below 100 °C, a transition to a glass phase on melt-quenching, CO2 uptake, and its permanent porosity was confirmed using molecular dynamic simulations
Distributed cutting plane method via sample point consensus
No full textThis paper considers a general setup for the constrained convex optimisation problem over jointly-fully connected time-varying networks. We propose a novel cutting plane-based method that embeds a proximity-based consensus scheme for solving this (potentially non-smooth) optimisation problem. The consensus mechanism allows agents to select the same sample point and therefore reconstruct the centralised cut individually. Under convexity, we prove that agents' sample points converge to the optimal set of the global problem. Numerical tests show the performance of the algorithm
Reduced DJ-1–F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
No full textDisruption in neuronal and synaptic metabolic homeostasis is a key driver of neurodegeneration in Parkinson’s disease (PD). Mitochondrial activity, biomass, and efficiency are critical to this balance. While activity and biomass are well-characterized in PD pathology, mitochondrial metabolic efficiency remains insufficiently explored. Our previous studies showed that the protein product of PD-associated gene DJ-1 modulates metabolic efficiency through its interaction with the F1Fo-ATP-synthase β-subunit (β-sub). Here, using proximity ligation assay (PLA), we compared
mitochondrial DJ-1–β-sub association in distinct mesencephalic dopaminergic (mesDA) neuronal
subpopulations and their intracellular compartments of PD and control post-mortem brains. In PD brains, DJ-1–β-sub-PLA was lower than control in substantia nigra pars compacta (SNpc) somata and neurites but unchanged in ventral tegmental area (VTA) neurons. In PD and control cases, the PLA signal was reduced in distal neurites of SNpc compared to VTA neurons. These intracellular and region-specific differences suggest that impaired mitochondrial efficiency may contribute to the differential vulnerability of mesDA neurons in PD
A new solar-powered device for the treatment of neonatal hyperbilirubinemia in hardest-to-reach places tested in Nigeria
No full textBackground Information: The treatment of hyper bilirubinaemia in faraway remote locations of the world, where grid electricity and specialist doctors are unavailable, is hampered by a lack of appropriate technologies that could be operable by basic-trained healthcare workers. Hence the urgent need for the development of simplified low-cost medical devices that could be deployable to the hardest-to-reach remote locations of the world.
Methods: Low-cost stable elements, components, and workpieces were targeted and applied in design to develop an applicable intensive phototherapy machine. Materials were sourced from in-country local markets to prototype the resultant device for capacity tests, and technical and safety assessments. The device was crafted to be solely solar energy dependent for power sustainability and climate-change mitigation in remote locations prior to ethical-approval and commencement of clinical trialling at University of Calabar Teaching Hospital Nigeria, to determine its efficiency in rapid breakdown of ‘severe’ serum bilirubin to a ‘mild’ benchmark level.
Result: The new device passed all technical safety assessments, delivering a total body irradiation treatment capacity of 45—158 µW/cm2/nm with 460 nm light wavelengths across various aspects of the body of a neonate. The device utilises real-time solar-power whilst self-banking its private reserve energy, which could last for over 27 hours when no-real-time energy from the sun is available. All initial eleven patients enrolled during the first 3-months of trialling were safely and successfully treated within 17.8 ± 8.7 irradiation-hours with stable vital-signs and no injuries.
Conclusion: The new device is a potentially sustainable LMIC-solution for severe jaundice management
Counterfactual scenarios for automated planning
No full textCounterfactual Explanations (CEs) are a powerful technique used to explain Machine Learning models by showing how the input to a model should be minimally changed for the model to produce a different output. Similar proposals have been made in the context of Automated Planning, where CEs have been characterised in terms of minimal modifications to an existing plan that would result in the satisfaction of a different goal. While such explanations may help diagnose faults and reason about the characteristics of a plan, they fail to capture higher-level properties of the problem being solved. To address this limitation, we propose a novel explanation paradigm that is based on counterfactual scenarios. In particular, given a planning problem P and an LTLf formula ψ defining desired properties of a plan, counterfactual scenarios identify minimal modifications to P such that it admits plans that comply with ψ. In this paper, we present two qualitative instantiations of counterfactual scenarios based on an explicit quantification over plans that must satisfy ψ. We then characterise the computational complexity of generating such counterfactual scenarios when different types of changes are allowed on P. We show that producing counterfactual scenarios is often only as expensive as computing a plan for P , thus demonstrating the practical viability of our proposal and ultimately providing a framework to construct practical algorithms in this area
Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study
No full textImportance
The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) vs non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months.
Objective
To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD.
Design
Phase 3, open-label, single-arm long-term extension study (SUSTAIN-3) conducted from June 2016 to December 2022.
Setting
Outpatient.
Participants
Adults with TRD who participated in ≥1 of 6 phase 3 “parent” studies continued esketamine by either entering a 4-week induction phase followed by an optimization/maintenance phase of variable duration (n = 458) or directly entering the optimization/maintenance phase of SUSTAIN-3 (n = 690), based on their individual response to study drug at the endpoint of the parent study.
Interventions
Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance (weekly, every-other-week, or every-4-weeks), under direct supervision by site staff.
Main Outcomes and Measures
To assess the long-term safety of esketamine. Efficacy endpoints included the change in depressive symptoms, assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).
Results
A total of 1148 patients were enrolled. Total exposure to esketamine was 3777 cumulative patient-years. Mean (median, range) exposure to esketamine in SUSTAIN-3 was 42.9 (45.8, range 0-79) months. The most common adverse events were headache (36.9%), dizziness (33.9%), nausea (33.6%), dissociation (25.5%), nasopharyngitis (23.8%), somnolence (23.1%), dysgeusia (20.2%), and back pain (20.0%). During the study, 5.3% and 6.4% of participants discontinued due to lack of efficacy or adverse event, respectively. Nine participants died: COVID-19-related (n = 3), pneumonia (n = 2), and completed suicide, myocardial infarction, multiple injuries, unknown cause (n = 1 each). The mean MADRS total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from baseline-to-phase endpoint of each phase: induction: −12.8 [9.73]; optimization/maintenance: + 0.2 [9.93]). A total of 35.6% of participants were in remission at the induction endpoint, and 48.5% and 49.6% at week 112 and optimization/maintenance endpoint, respectively.
Conclusions and Relevance
In the SUSTAIN-3 final dataset, no new safety signals were identified during long-term treatment with intermittently-dosed esketamine, combined with oral antidepressant, and improvement in depression generally persisted among participants who remained on maintenance treatment. These results add to the accumulated evidence on TRD treatment with esketamine.
Trial Registration
clinicaltrials.gov identifier: NCT02782104
Modelling of carbon nanotube-based sensors for structural health monitoring applications
No full textDespite substantial experimental progress, predictive numerical models that quantitatively link micro-scale damage mechanisms in carbon nanotube (CNT) composites to the macroscopic piezoresistive signal required for Structural Health Monitoring (SHM) remain scarce. To close this gap, this thesis develops and validates the micromechanical behaviour and fracture modelling of CNT-based composites, focusing on their self-sensing capabilities and on providing a quantitative modelling framework for SHM. While CNTs exhibit exceptional mechanical and electrical properties, their performance is limited by challenges such as dispersion and agglomeration. Advanced modelling techniques combining mean-field homogenization (MFH), FEM, and phase field fracture models address these issues.
A MFH framework is developed to predict the elastic properties of CNT-reinforced composites, considering CNT geometry, orientation and agglomeration. A two-parameter agglomeration model is utilised to quantify clustering's impact combined with a micromechanical fracture framework, which incorporates CNT pull-out and rupture mechanisms to predict fracture behaviour and toughening effects. Agglomeration decreases toughness by facilitating pull-out through reduced interfacial area and weaker stress transfer.
The thesis explores electrical and self-sensing CNT composites, modelling conductivity and piezoresistivity for structural SHM applications. A new electromechanical phase field fracture framework integrates MFH, piezoresistivity, and phase field methods to predict crack initiation and propagation under electromechanical loading. Computational experiments validate stress–strain and resistance predictions and simulate complex interactions.
Finally, the framework is applied to self-sensing smart concrete in reinforced-concrete structures, integrating piezoresistive equations and phase field fracture modelling with three-dimensional truss elements for electrodes, which can be extrapolated as rebars. Experimental validation confirms its predictive capabilities for SHM applications.
By providing the first validated, fracture–piezoresistive model of CNT composites, this thesis delivers a novel design and assessment tool for SHM systems and advances the broader field of multifunctional materials. Its findings contribute to materials science and structural engineering, advancing the development of smart and efficient composites.Open Acces