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A three-dimensional robust nonlinear cooperative guidance law is proposed to address the challenge of multiple missiles intercepting manoeuvering targets under stringent input constraints and thruster failure. The finite-time convergence theory is used to design a distributed nonlinear sliding mode guidance law, ensuring that the system converges in finite time, with the upper limit of convergence time related to the initial state. A nonlinear sliding surface is adopted to mitigate actuator saturation issues. Then, considering thruster failure, a robust cooperative guidance law is further introduced, ensuring mission completion through the reconstruction of the guidance law. The closed-loop system is proven to be stable using Lyapunov theory, and the influence of hyperparameters on the cooperative guidance law is analysed. Additionally, the results of numerical simulations and hardware-in-the-loop experiments demonstrate the effectiveness and robustness of the proposed algorithm in dealing with stringent input saturation and various disturbances.
Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.
Methods
This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).
Results
In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.
Conclusions
Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.
Metabolic enzymes are the catalysts that drive the biochemical reactions essential for sustaining life. Many of these enzymes are tightly regulated by feedback mechanisms. To fully understand their roles and modulation, it is crucial to investigate the relationship between their structure, catalytic mechanism, and function. In this perspective, by using three examples from our studies on Mycobacterium tuberculosis (Mtb) isocitrate lyase and related proteins, we highlight how an integrated approach combining structural, activity, and biophysical data provides insights into their biological functions. These examples underscore the importance of employing fast-fail experiments at the early stages of a research project, emphasise the value of complementary techniques in validating findings, and demonstrate how in vitro data combined with chemical, biochemical, and physiological knowledge can lead to a broader understanding of metabolic adaptations in pathogenic bacteria. Finally, we address the unexplored questions in Mtb metabolism and discuss how we expand our approach to include microbiological and bioanalytical techniques to further our understanding. Such an integrated and interdisciplinary strategy has the potential to uncover novel regulatory mechanisms and identify new therapeutic opportunities for the eradication of tuberculosis. The approach can also be broadly applied to investigate other biochemical networks and complex biological systems.
A careful theoretical analysis of the excitation of Alfvén eigenmodes (AEs), such as TAE (toroidicity-induced AE) and RSAE (reversed shear AE), by superalfvenic energetic particles is required for reliable predictions of energetic ion relaxation in present day fusion experiments. This includes the evaluation of different AE damping mechanisms including radiative and continuum dampings which are the focus of this study. A recent comprehensive benchmark of different eigenmode solvers including gyrokinetic, gyrofluid and hybrid magenetohydrodynamics (MHD) has shown that employed models may have deficiencies when addressing some of them (Taimourzadeh et al., Nucl. Fusion, vol. 59, 2019, 066006). In this paper, we are studying the radiative and continuum dampings of RSAEs in details which were missing in hybrid NOVA/NOVA-C calculations to prepare a NOVA-C package with a substantial upgrade. Both dampings require the finite Larmor radius (FLR) corrections to AE mode structures to be accounted for. Accurately calculating different damping rates and understanding their parametric dependencies, we resolve the limitation coming out of the perturbative approach. In particular, here, the radiative damping is included perturbatively, whereas the continuum damping is computed non-perturbatively. Our comparison leads to the conclusion that the non-perturbative treatment of the unstable RSAE modes is needed to find the agreement with the gyrokinetic calculations. We expect that the RSAE mode structure modification plays a dominant role in determining the RSAE stability.
In this paper, a brand-new adaptive fault-tolerant non-affine integrated guidance and control method based on reinforcement learning is proposed for a class of skid-to-turn (STT) missile. Firstly, considering the non-affine characteristics of the missile, a new non-affine integrated guidance and control (NAIGC) design model is constructed. For the NAIGC system, an adaptive expansion integral system is introduced to address the issue of challenging control brought on by the non-affine form of the control signal. Subsequently, the hyperbolic tangent function and adaptive boundary estimation are utilised to lessen the jitter due to disturbances in the control system and the deviation caused by actuator failures while taking into account the uncertainty in the NAIGC system. Importantly, actor-critic is introduced into the control framework, where the actor network aims to deal with the multiple uncertainties of the subsystem and generate the control input based on the critic results. Eventually, not only is the stability of the NAIGC closed-loop system demonstrated using Lyapunov theory, but also the validity and superiority of the method are verified by numerical simulations.
With the development of overall design methodologies for hypersonic vehicles and their propulsion systems, nozzles should expand airflow in a short length and provide sufficient thrust. Therefore, the large expansion ratio single expansion ramp nozzle (LSERN) is widely used. The form of the overexpanded flow field in the nozzle is complex, under the conditions of nozzle start-up, low speed and low nozzle pressure ratio (NPR), thereby negatively influencing the entire propulsion system. Thus, the nozzle flow separation pattern and the key factors affecting the flow separation pattern also deserve considerable attention. In this study, the design of SERN is completed using the cubic curve design method, and the model is numerically simulated for specific operating conditions to study the flow separation patterns and the transition processes of different patterns. Furthermore, the key factors affecting the various flow separation patterns in the nozzle are investigated in detail. Results show that the LSERN in different NPRs appeared in two types of restricted shock separation (RSS) pattern and free shock separation (FSS) pattern, as well as their corresponding flow separation pattern transition processes. The initial expansion angle and the nozzle length affect the range of NPRs maintained by the FSS pattern. The initial expansion angle affects the pattern of flow separation, whereas the nozzle length remarkably influences the critical NPR during transition.
Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
The occurrence of depression in adolescence, a critical period of brain development, linked with neuroanatomical and cognitive abnormalities. Neuroimaging studies have identified hippocampal abnormalities in those of adolescent patients. However, few studies have investigated the atypically developmental trends in hippocampal subfields in adolescents with depression and their relationships with cognitive dysfunctions.
Objectives
To explore the structural abnormalities of hippocampal subfields in patients with youth depression and examine how these abnormalities associated with cognitive deficits.
Methods
We included a sample of 79 first-episode depressive patients (17 males, age = 15.54±1.83) and 71 healthy controls (23 males, age = 16.18±2.85). The severity of these adolescent patients was assessed by depression scale, suicidal risk and self-harm behavior. Nine cognitive tasks were used to evaluate memory, cognitive control and attention abilities for all participants. Bilateral hippocampus were segmented into 12 subfields with T1 and T2 weighted images using Freesurfer v6.0. A mixed analysis of variance was performed to assess the differences in subfields volumes between all patients and controls, and between patients with mild and severe depression. Finally, LASSO regression was conducted to explore the associations between hippocampal subfields and cognitive abnormalities in patients.
Results
We found significant subfields atrophy in the CA1, CA2/3, CA4, dentate gyrus, hippocampal fissure, hippocampal tail and molecular layer subfields in patients. For those patients with severe depression, hippocampal subfields showed greater extensive atrophy than those in mild, particularly in CA1-4 subfields extending towards the subiculum. These results were similar across various severity assessments. Regression indicated that hippocampal subfields abnormalities had the strongest associations with memory dysfunction, and relatively week associations with cognitive control and attention. Notably, CA4 and dentate gyrus had the highest weights in the regression model.
Conclusions
As depressive severity increases, hippocampal subfield atrophy tends to spread from CA regions to surrounding areas, and primarily affects memory function in patients with youth depression. These results suggest hippocampus might be markers in progression of adolescent depression, offering new directions for early clinical intervention.
Among the various patient experiences, cancer-related fatigue and sleep disturbances emerge as pivotal aspects that can substantially impact individuals’ quality of life. There exists a relative scarcity of research focusing on the intricate relationship between symptoms, functioning, fatigue, and sleep disturbances in colorectal cancer (CRC) patients.
Objectives
In this context, the current research endeavors to apply advanced statistical methodologies to elucidate the complex relationships between symptoms, functioning, fatigue, and sleep disturbances. By exploring the intricate web of patient characteristics, clinical factors, psychosocial elements, this study aims to construct a holistic model that not only captures the nuances of colorectal cancer patients’ experiences but also uncovers potential avenues for intervention and support.
Methods
In our cross sectional study, we administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Quality of Life Questionnaire Colorectal Cancer Module (QLQ-CR29) to 987patients who were surgically-treated for CRC from the tertiary hospital from 2013 through 2018. To confirm the relationship between symptoms of CRC patients, univariable logistic regression was used to examine the potential relationship between independent variables and the occurrence of fatigue and sleep disorders. Least Absolute Shrinkage and Selection Operator (Lasso) was used for variable selection. The selected variables were then applied to a multivariate logistic regression analysis to examine the most influential predictors of fatigue and sleep disturbance. Finally, gaussian graphical models (GGM) were used to identify potential interactions between characteristics, symptoms, functioning, with fatigue, and sleep disturbances in CRC. In this study, Directed Acyclic Graph (DAG) was used to identify causal dependancy and path of variables.
Results
About 10.4% of study participants reported experiencing fatigue. Sleep problems were reported by 15.8% of the study participants. Multivariable logistic regression analysis using Lasso showed that sleep problem (odds ratio [OR]=2.34; 95% CI, 1.03-5.31), physical, role, and emotional functioning, pain, dyspnoea, and appetite loss were significant predictors of fatigue, while emotional functioning, dyspnoea, and appetite loss were significant predictors of sleep problem. The variables that were directly linked to fatigue were role functioning, emotional functioning, dyspnoea, appetite loss, body image and trouble with taste. The variables that were directly linked to sleep problem were emotional functioning and appetite loss.
Conclusions
In conclusion, there were complex relationships between symptoms, functioning, fatigue, and sleep disturbances. The symptom network of CRC patients showed different patterns toward fatigue and sleep.
For the launch vehicle attitude control problem, traditional methods can seldom accurately identify the fault types, making the control method lack of pertinence, which largely affects the effect of attitude control. This paper proposes an active fault tolerant control strategy, which mainly includes fault diagnosis and fault tolerant control. In the fault diagnosis part, a small deviation attitude dynamics model of the launch vehicle is established, Kalman filters with different structures are designed to detect and isolate faults through residual changes, and the fault quantity of the actuator is further estimated. In the fault tolerant control part, the following control scheme is adopted according to the above diagnostic information: when the sensor fault is detected, the sensor measurement data is reconstructed; when the actuator fault is identified, the control allocation matrix is reconstructed. Simulation results show that the proposed method can effectively diagnose sensor fault and actuator faults, and significantly improve attitude tracking accuracy and control adjustment time.
Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.
Methods:
We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.
Results:
We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.
Conclusion:
PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.
Redox and acid-base reactions play important roles in the fate of metal contaminants in soils and sediments. The presence of significant amounts of Cr, Pb and other toxic heavy metals in contaminated soils and sediments is of great environmental concern. Oxidation states and dissolution characteristics of the heavy metals can exert negative effects on the natural environment. Atomic force microscopy (AFM) was used to follow the changes in morphology and structure of reaction products of Cr and Pb formed on mineral surfaces. Nitrate salts of Cr(III) and Pb(II) were used to replace the native exchangeable cations on muscovite and smectite surfaces and the metal-mineral systems were then reacted at different pH's and redox conditions.
For Pb, aggregate morphological forms were found at pH 6.1 and 12.4. At pH 6.1, the mean roughness value was 0.70 nm, and at pH 12.4 it was 5.30 nm. The fractal dimensions were 2.03 at pH 6.1 and 2.05 at pH 12.4. For Cr(III), both layered and aggregate morphological forms were found at pH 6.8 and 10.8. The mean roughness values were 0.90 nm at pH 6.8 and 4.3 nm at pH 10.8. Fractal dimensions for both were 2.00. The effect of redox conditions on morphological characteristics was studied on a smectite substrate. The reduced clays were more compacted than oxidized ones and the reduced clay could reduce Cr(VI) to Cr(III), forming new minerals on the surfaces.
A geochemical equilibrium model, MINTEQA2, was used to simulate the experimental conditions and predict possible reaction products. Simulation results agreed well with data from experiments, providing evidence that modeling can provide a useful “reality check” for such studies. Together, MINTEQA2 and AFM can provide important information for evaluating the morphologies and chemical reactivities of metal reaction products formed on phyllosilicate surfaces under varying environmental conditions.
Redox properties of iron-bearing mineral surfaces may play an important role in controlling the transport and transformation of pollutants into ground waters. Suspensions of seven iron-bearing minerals were reacted with pH and redox indicators under anaerobic conditions at the pH of the natural suspension. The responses of the indicators to the mineral surfaces were monitored by UV-visible spectroscopy using a scattered transmission technique. The Hammett surface acidity function (Hs) and the surface redox potential (Ehs) of these iron-bearing minerals were measured. These measured values were used to calculate Eh values for the seven minerals: goethite = +293 mV; chlorite = +290 mV; hematite = +290 mV; almandite = +282 mV; ferruginous smectite = +275 mV; pyrite = +235 mV; and Na-vermiculite = +223 mV. Calculated surface redox potentials of minerals are different from their potentials measured by platinum electrode in bulk suspensions. UV-visible spectroscopy provides a quick and non-destructive way of monitoring organic probe response at the mineral surface.
Terahertz (THz) radiation from a plasma cylinder with embedded radial electric and axial magnetic fields is investigated. The plasma density and the electric and magnetic fields are such that the electron plasma frequency is near the electron cyclotron frequency and in the THz regime. Two-dimensional particle-in-cell simulations show that the plasma electrons oscillate not only in the azimuthal direction but also in the radial direction. Spectral analysis shows that the resulting oscillating current pattern has a clearly defined characteristic frequency near the electron cyclotron frequency, suggesting resonance between the cyclotron and plasma oscillations. The resulting far-field THz radiation in the axial direction is also discussed.
We provide an updated estimate of adult stroke event rates by age group, sex, and stroke type using Canadian administrative data. In the 2017–2018 fiscal year, there were an estimated 81,781 hospital or emergency department visits for stroke events in Canada, excluding Quebec. Our findings show that overall, the event rate of stroke is similar between women and men. There were slight differences in stroke event rate at various ages by sex and stroke type and emerging patterns warrant attention in future studies. Our findings emphasize the importance of continuous surveillance to monitor the epidemiology of stroke in Canada.
Background: Lower socioeconomic status is associated with worse outcomes after stroke. We evaluated the differences in acute revascularization treatments in patients with acute ischemic stroke (AIS) who were materially deprived compared to those who were not. Methods: In a population-based cohort study, we used linked administrative data to identify community-dwelling adults hospitalized for AIS between 2017-2022 in Ontario, Canada. The main exposure was neighborhood-level material deprivation quintiles. Multivariable logistic regression was used to obtain the adjusted odds ratio (aOR) of receiving revascularization treatments (thrombolysis or thrombectomy) for patients in each deprivation quintile compared to the least deprived quintile. Results: We identified 57,709 patients (median age 74 years; 45.9% female). Compared to patients in the least deprived quintile, those with higher deprivation were younger and more likely to have hypertension and diabetes, but less likely to have atrial fibrillation. Compared to patients in the least deprived quintile, fewer patients in the very deprived quintile (17.9% vs 19.6%, aOR 0.88, 95%CI [0.82,0.95]) and in the most deprived quintile (16.6% vs 19.6%, 0.77 [0.71,0.83]) received revascularization treatments. Conclusions: Our results suggest disparities in the use of acute ischemic stroke revascularization treatments by socioeconomic status despite access to universal health care.
With an immersed-boundary lattice-Boltzmann method, we consider the transit of a three-dimensional initially spherical capsule with a viscoelastic membrane through a cross-slot microchannel. The capsule is released with a small initial off-centre distance in the feeding channel, to mimic experiments where capsules or cells are not perfectly aligned with the centreline. Our main objective is to establish the phase diagram of the capsule's deformation modes as a function of the flow inertia and capsule membrane viscosity. We mainly find three deformation modes in the channel cross-slot. For a capsule with low membrane viscosity, a quasi-steady mode occurs at low Reynolds numbers ($Re$), in which the capsule can reach and maintain a steady ellipsoidal shape near the stagnation point, for a considerable time period. With $Re$ increasing to 20, an overshoot–retract mode is observed. The capsule deformation oscillates on an inertial–elastic time scale, suggesting that the dynamics is mainly driven by the balance of the inertial and membrane elastic forces. The membrane viscosity slows down the capsule deformation and suppresses the overshoot–retract mode. A capsule with high membrane viscosity undergoes a continuous-elongation mode, in which its deformation keeps increasing during most of its journey in the channel cross-slot. We summarise the results in phase diagrams, and propose a scaling model which can predict the deformation modes of a viscoelastic capsule in the inertial flow regime. We also discuss implications of the present findings for practical experiments for mechanical characterisation of capsules or cells.
Although age-standardized stroke occurrence has been decreasing, the absolute number of stroke events globally, and in Canada, is increasing. Stroke surveillance is necessary for health services planning, informing research design, and public health messaging. We used administrative data to estimate the number of stroke events resulting in hospital or emergency department presentation across Canada in the 2017–18 fiscal year.
Methods:
Hospitalization data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database and the Ministry of Health and Social Services in Quebec. Emergency department data were obtained from the CIHI National Ambulatory Care Reporting System (Alberta and Ontario). Stroke events were identified using ICD-10 coding. Data were linked into episodes of care to account for readmissions and interfacility transfers. Projections for emergency department visits for provinces/territories outside of Alberta and Ontario were generated based upon age and sex-standardized estimates from Alberta and Ontario.
Results:
In the 2017–18 fiscal year, there were 108,707 stroke events resulting in hospital or emergency department presentation across the country. This was made up of 54,357 events resulting in hospital admission and 54,350 events resulting in only emergency department presentation. The events resulting in only emergency department presentation consisted of 25,941 events observed in Alberta and Ontario and a projection of 28,409 events across the rest of the country.
Conclusions:
We estimate a stroke event resulting in hospital or emergency department presentation occurs every 5 minutes in Canada.