This paper studies the problem of time-varying formation control with finite-time prescribed performance for nonstrict feedback second-order multi-agent systems with unmeasured states and unknown nonlinearities.To eli...This paper studies the problem of time-varying formation control with finite-time prescribed performance for nonstrict feedback second-order multi-agent systems with unmeasured states and unknown nonlinearities.To eliminate nonlinearities,neural networks are applied to approximate the inherent dynamics of the system.In addition,due to the limitations of the actual working conditions,each follower agent can only obtain the locally measurable partial state information of the leader agent.To address this problem,a neural network state observer based on the leader state information is designed.Then,a finite-time prescribed performance adaptive output feedback control strategy is proposed by restricting the sliding mode surface to a prescribed region,which ensures that the closed-loop system has practical finite-time stability and that formation errors of the multi-agent systems converge to the prescribed performance bound in finite time.Finally,a numerical simulation is provided to demonstrate the practicality and effectiveness of the developed algorithm.展开更多
BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To ex...BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.展开更多
The undesirable dendrite growth induced by non-planar zinc(Zn)deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially im...The undesirable dendrite growth induced by non-planar zinc(Zn)deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries(ZMBs).Herein,we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium(Zn-In)interface in the microchannels.The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities.Meanwhile,electron aggregation accelerates the dissolution of non-(002)plane Zn atoms on the array surface,thereby directing the subsequent homoepitaxial Zn deposition on the array surface.Consequently,the planar dendrite-free Zn deposition and long-term cycling stability are achieved(5,050 h at 10.0 mA cm^(−2) and 27,000 cycles at 20.0 mA cm^(−2)).Furthermore,a Zn/I_(2) full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C,demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.展开更多
The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted...The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.展开更多
Experiments are conducted on the evacuation rate of pedestrians through exits with queued evacuation pattern and random evacuation pattern. The experimental results show that the flow rate of pedestrians is larger wit...Experiments are conducted on the evacuation rate of pedestrians through exits with queued evacuation pattern and random evacuation pattern. The experimental results show that the flow rate of pedestrians is larger with the random evacuation pattern than with the queued evacuation pattern. Therefore, the exit width calculated based on the minimum evacuation clear width for every 100 persons, which is on the assumption that the pedestrians pass through the exit in one queue or several queues, is conservative. The number of people crossing the exit simultaneously is greater in the random evacuation experiments than in the queued evacuation experiments, and the time interval between the front row and rear row of people is shortened in large-exit conditions when pedestrians evacuate randomly. The difference between the flow rate with a queued evacuation pattern and the flow rate with a random evacuation pattern is related to the surplus width of the exit, which is greater than the total width of all accommodated people streams. Two dimensionless quantities are defined to explore this relationship. It is found that the difference in flow rate between the two evacuation patterns is stable at a low level when the surplus width of the exit is no more than 45% of the width of a single pedestrian stream. There is a great difference between the flow rate with the queued evacuation pattern and the flow rate with the random evacuation pattern in a scenario with a larger surplus width of the exit. Meanwhile, the pedestrians crowd extraordinarily at the exit in these conditions as well, since the number of pedestrians who want to evacuate through exit simultaneously greatly exceeds the accommodated level. Therefore, the surplus width of exit should be limited especially in the narrow exit condition, and the relationship between the two dimensionless quantities mentioned above could provide the basis to some extent.展开更多
Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics b...Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics beyond this approach is based on the analysis of the blood oxygenation level-dependent signal.展开更多
Recent research in cross-domain intelligence fault diagnosis of machinery still has some problems,such as relatively ideal speed conditions and sample conditions.In engineering practice,the rotational speed of the mac...Recent research in cross-domain intelligence fault diagnosis of machinery still has some problems,such as relatively ideal speed conditions and sample conditions.In engineering practice,the rotational speed of the machine is often transient and time-varying,which makes the sample annotation increasingly expensive.Meanwhile,the number of samples collected from different health states is often unbalanced.To deal with the above challenges,a complementary-label(CL)adversarial domain adaptation fault diagnosis network(CLADAN)is proposed under time-varying rotational speed and weakly-supervised conditions.In the weakly supervised learning condition,machine prior information is used for sample annotation via cost-friendly complementary label learning.A diagnosticmodel learning strategywith discretized category probabilities is designed to avoidmulti-peak distribution of prediction results.In adversarial training process,we developed virtual adversarial regularization(VAR)strategy,which further enhances the robustness of the model by adding adversarial perturbations in the target domain.Comparative experiments on two case studies validated the superior performance of the proposed method.展开更多
In time-variant reliability problems,there are a lot of uncertain variables from different sources.Therefore,it is important to consider these uncertainties in engineering.In addition,time-variant reliability problems...In time-variant reliability problems,there are a lot of uncertain variables from different sources.Therefore,it is important to consider these uncertainties in engineering.In addition,time-variant reliability problems typically involve a complexmultilevel nested optimization problem,which can result in an enormous amount of computation.To this end,this paper studies the time-variant reliability evaluation of structures with stochastic and bounded uncertainties using a mixed probability and convex set model.In this method,the stochastic process of a limit-state function with mixed uncertain parameters is first discretized and then converted into a timeindependent reliability problem.Further,to solve the double nested optimization problem in hybrid reliability calculation,an efficient iterative scheme is designed in standard uncertainty space to determine the most probable point(MPP).The limit state function is linearized at these points,and an innovative random variable is defined to solve the equivalent static reliability analysis model.The effectiveness of the proposed method is verified by two benchmark numerical examples and a practical engineering problem.展开更多
Hybrid precoding is considered as a promising low-cost technique for millimeter wave(mm-wave)massive Multi-Input Multi-Output(MIMO)systems.In this work,referring to the time-varying propagation circumstances,with semi...Hybrid precoding is considered as a promising low-cost technique for millimeter wave(mm-wave)massive Multi-Input Multi-Output(MIMO)systems.In this work,referring to the time-varying propagation circumstances,with semi-supervised Incremental Learning(IL),we propose an online hybrid beamforming scheme.Firstly,given the constraint of constant modulus on analog beamformer and combiner,we propose a new broadnetwork-based structure for the design model of hybrid beamforming.Compared with the existing network structure,the proposed network structure can achieve better transmission performance and lower complexity.Moreover,to enhance the efficiency of IL further,by combining the semi-supervised graph with IL,we propose a hybrid beamforming scheme based on chunk-by-chunk semi-supervised learning,where only few transmissions are required to calculate the label and all other unlabelled transmissions would also be put into a training data chunk.Unlike the existing single-by-single approach where transmissions during the model update are not taken into the consideration of model update,all transmissions,even the ones during the model update,would make contributions to model update in the proposed method.During the model update,the amount of unlabelled transmissions is very large and they also carry some information,the prediction performance can be enhanced to some extent by these unlabelled channel data.Simulation results demonstrate the spectral efficiency of the proposed method outperforms that of the existing single-by-single approach.Besides,we prove the general complexity of the proposed method is lower than that of the existing approach and give the condition under which its absolute complexity outperforms that of the existing approach.展开更多
The purpose of the study was to evaluate the sperm viability of semen infected with PRRSV viral particles, observing the effect of the Virus on the motility of boar sperm. The work was carried out at the FMVZ-BUAP Gen...The purpose of the study was to evaluate the sperm viability of semen infected with PRRSV viral particles, observing the effect of the Virus on the motility of boar sperm. The work was carried out at the FMVZ-BUAP Genetics and Reproduction Laboratory. 5 stallions were used. Each sample contained 1 × 10<sup>6</sup> sperm, the PRRS virus strain was ATCC-VR-2332 (0, 10<sup>2</sup>, 10<sup>4</sup> and 10<sup>6</sup> copies of RNA/mL in triplicate), it was observed daily at the CASA;Hamilton Thorne<sup>®</sup>. Cells with MT (P < 0.05) on days 1, 3, 5, 7 and 10 of evaluation with 201 ± 7.3, 167 ± 10.1, 165 ± 14.6, 134 ± 8.2 and 120 ± 8.8, respectively. The % MP between control and virus concentrations (P ≥ 0.05). The LCV on day 1 and 7 PI at 10X<sup>2</sup> and 10X<sup>6</sup> (P < 0.05) vs control. In the Correlation Matrix, where it is observed that there is a correlation between VSL and VAP, VSL and VCL, VCL and ALH, VAP with ALH. There is a correlation of VSL and ALH, STR and ALH. In this study there were (P ≤ 0.01) in the VCL, in the concentrations (10<sup>2</sup>) 162.81 ± 10.65 and (10<sup>6</sup>) 177.12 ± 5.77 vs 193.04 ± 4.62 of control. This indicates that altering these parameters would be related to fertility and the PRRS virus affects the LCV. Regarding the VSL, it was observed that the sperm infected with viruses 10<sup>2</sup>, 10<sup>4</sup> and 10<sup>6</sup> of 48.00 ± 3.38, 49.88 ± 1.83 and 50.55 ± 2.24 Vs. 56.66 ± 1.68 of control respectively, the control would have greater possibilities of fertilizing the oocyte. In this study, it was found (P ≤ 0.01) in the VAP with 102 of 77.26 ± 5.16, 10<sup>4</sup> with 83.35 ± 2.41 and 10<sup>6</sup> with 81.29 ± 3.14 vs the control with 90.56 ± 2.07. Regarding the ALH there is (P < 0.05) a 10<sup>4</sup> with 8.70 ± .26 and 10<sup>6</sup> with 9.64 ± 0.23 vs control 8.50 ± 0.27. The presence of different concentrations of PRRSV in boar semen induces changes in different types of sperm motility. Infection of ejaculates with the PRRS virus affects sperm motility on days 1, 3, 5, 7, and 10 post-infections.展开更多
For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further agg...For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further aggravates the spatial difference of the flow field.In this study,the displacement experiments were employed to investigate the variations in core permeability,porosity,and relative permeability after a large amount of water injection.A relative permeability endpoint model was proposed by utilizing the alternating conditional expectation(ACE)transformation to describe the variation in relative permeability based on the experimental data.Based on the time dependent models for permeability and relative permeability,the traditional oil-water two-phase model was improved and discretized using the mimetic finite difference method(MFD).The two cases were launched to confirm the validation of the proposed model.The impact of time-varying physical features on reservoir production performance was studied in a real water flooding reservoir.The experimental results indicate that the overall relative permeability curve shifts to the right as water injection increases.This shift corresponds to a transition towards a more hydrophilic wettability and a decrease in residual oil saturation.The endpoint model demonstrates excellent accuracy and can be applied to time-varying simulations of reservoir physics.The impact of variations in permeability and relative permeability on the reservoir production performance yields two distinct outcomes.The time-varying permeability of the reservoir results in intensified water channeling and poor development effects.On the other hand,the time-varying relative permeability enhances the oil phase seepage capacity,facilitating oil displacement.The comprehensive time-varying behavior is the result of the combined influence of these two parameters,which closely resemble the actual conditions observed in oil field exploitation.The time-varying simulation technique of reservoir physical properties proposed in this paper can continuously and stably characterize the dynamic changes of reservoir physical properties during water drive development.This approach ensures the reliability of the simulation results regarding residual oil distribution.展开更多
Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of si...Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of similarity sets, and proposes a Portfolio Selection Method based on Pattern Matching with Dual Information of Direction and Distance (PMDI). By studying different combination methods of indicators such as Euclidean distance, Chebyshev distance, and correlation coefficient, important information such as direction and distance in stock historical price information is extracted, thereby filtering out the similarity set required for pattern matching based investment portfolio selection algorithms. A large number of experiments conducted on two datasets of real stock markets have shown that PMDI outperforms other algorithms in balancing income and risk. Therefore, it is suitable for the financial environment in the real world.展开更多
Background: Cardiovascular diseases are the leading cause of death in India, with coronary artery disease (CAD) accounting for a majority of the deaths. There are few large registries on acute coronary syndrome (ACS) ...Background: Cardiovascular diseases are the leading cause of death in India, with coronary artery disease (CAD) accounting for a majority of the deaths. There are few large registries on acute coronary syndrome (ACS) from India. Our aim is to study the clinical and epidemiological profile of ACS PATIENTS presenting to our institute, including their angiographic features. Methods: This hospital-based observational, single tertiary care center, prospective study was conducted on patients admitted in the Department of Cardiology at a tertiary care center in Haryana. The study included 400 patients aged greater than 18 years who were admitted with the diagnosis of ACS, and it was carried out for 1 year. The epidemiological profile, clinical history, risk factors, electrocardiogram findings, and angiographic pattern were studied and analyzed with appropriate statistical tools. Results: The mean age of the study population was 55.12 ± 11.78 years. Male and female ratio was 2.4:1. The majority of the patients came from rural background (80%);24% of the patients were illiterate. Smoking was the most common risk factor (51.5%) in our study population followed by hypertension (40%) and diabetes (28%). Unstable angina was the most common type of ACS, which was found in 68.25% of patients. Premature CAD was found in 27.8% of patients and obstructive CAD was found in 63% of patients. Coronary angiography revealed that 39% had single vessel disease (SVD), 23.5% had double vessel disease (DVD), and 27.5% had triple vessel disease (TVD). LAD was more commonly involved, followed by RCA and LCX. Within the first 24 hours, 67% of patients sought medical assistance and only 38.5% received definitive treatment, suggesting a delay in seeking definitive treatment in our study population. Conclusion: The study suggests that unstable angina is the most common form of ACS in the study population, which is mostly of rural background with significant delay in seeking medical help. Smoking is the most common risk factor in the study population.展开更多
A simulated oil viscosity prediction model is established according to the relationship between simulated oil viscosity and geometric mean value of T2spectrum,and the time-varying law of simulated oil viscosity in por...A simulated oil viscosity prediction model is established according to the relationship between simulated oil viscosity and geometric mean value of T2spectrum,and the time-varying law of simulated oil viscosity in porous media is quantitatively characterized by nuclear magnetic resonance(NMR)experiments of high multiple waterflooding.A new NMR wettability index formula is derived based on NMR relaxation theory to quantitatively characterize the time-varying law of rock wettability during waterflooding combined with high-multiple waterflooding experiment in sandstone cores.The remaining oil viscosity in the core is positively correlated with the displacing water multiple.The remaining oil viscosity increases rapidly when the displacing water multiple is low,and increases slowly when the displacing water multiple is high.The variation of remaining oil viscosity is related to the reservoir heterogeneity.The stronger the reservoir homogeneity,the higher the content of heavy components in the remaining oil and the higher the viscosity.The reservoir wettability changes after water injection:the oil-wet reservoir changes into water-wet reservoir,while the water-wet reservoir becomes more hydrophilic;the degree of change enhances with the increase of displacing water multiple.There is a high correlation between the time-varying oil viscosity and the time-varying wettability,and the change of oil viscosity cannot be ignored.The NMR wettability index calculated by considering the change of oil viscosity is more consistent with the tested Amott(spontaneous imbibition)wettability index,which agrees more with the time-varying law of reservoir wettability.展开更多
Background: Health challenges that are difficult to manage at primary health centres should be referred to secondary health facilities, and if untreated, to the tertiary hospitals. A good referral should include the p...Background: Health challenges that are difficult to manage at primary health centres should be referred to secondary health facilities, and if untreated, to the tertiary hospitals. A good referral should include the patient’s biography, such as age, gender, tribe, religion, occupation, medical history, the reason for the referral, treatments received, and clinical diagnosis. Objectives: To evaluate the referral patterns, indications for referrals, and feto-maternal outcomes for obstetric patients who were referred to the University of Port Harcourt Teaching Hospital. Materials and Methods: A prospective study of patients admitted to the Obstetric unit from January 1, 2021, to December 31, 2022. Data was collected from patients while on admission or clinic visits and recorded in an excel spread sheet. Data was analyzed with the Statistical Package for Social Sciences (SPSS) version 25. Results: Of the 3469 patients were admitted to the obstetric unit, 1476 and 1993 were admitted in 2021 and 2022, respectively. Most (70.35%) of the patients were in the 20-34 years age group, parity 1-4 was the most frequent (66.49%), while 85.39% of patients were booked. 10.46% of the booked patients were referred from other facilities, whereas 89.54% of patients were booked at our facility from the onset. Most common indications of referrals were previous caesarean section (CS) at term (40.09%) and hypertensive disorders of pregnancy (17.59%). The outcome for 2021 indicated 17 maternal deaths, 132 fetal deaths and 1010 live births, giving maternal mortality ratio (MMR) as 1810.44 per 100,000 live births and perinatal mortality ratio (PMR) of 130.7 per 1000 births respectively. In 2022, there were 17 maternal deaths, 130 fetal deaths and 1297 deliveries, giving a MMR of 1399 per 100,000 live births and a PMR of 100.2 per 1000 births. Conclusion: The pattern of referral among obstetric patients in this study shows that a lot of the patients do not get adequate care at the lower cadre of the referral system, hence adequate facilities should be made available in primary and secondary health centres to tackle obstetric emergencies.展开更多
To analyze the effects of a time-varying viscosity on the penetration length of grouting,in this study cement slur-ries with varying water-cement ratios have been investigated using the Bingham’sfluidflow equation and ...To analyze the effects of a time-varying viscosity on the penetration length of grouting,in this study cement slur-ries with varying water-cement ratios have been investigated using the Bingham’sfluidflow equation and a dis-crete element method.Afluid-solid coupling numerical model has been introduced accordingly,and its accuracy has been validated through comparison of theoretical and numerical solutions.For different fracture forms(a single fracture,a branch fracture,and a fracture network),the influence of the time-varying viscosity on the slurry length range has been investigated,considering the change in the fracture aperture.The results show that under different fracture forms and the same grouting process conditions,the influence of the time-varying viscosity on the seepage length is 0.350 m.展开更多
Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative dif...Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative diffusion process.Here we study one-dimensional patterning systems with analytical derivation and numerical simulations.We find that the diffusion constant of the patterning molecules exhibits a nonmonotonic effect on the readout of the positional information from the concentration patterns.Specifically,there exists an optimal diffusion constant that maximizes the positional information.Moreover,we find that the energy dissipation due to the physical diffusion imposes a fundamental upper limit on the positional information.展开更多
The complex and volatile international landscape has significantly impacted global grain supply security. This study uses a complex network analysis model to examine the evolution and trends of the global major grain ...The complex and volatile international landscape has significantly impacted global grain supply security. This study uses a complex network analysis model to examine the evolution and trends of the global major grain trade from 1990 to 2020, focusing on network topology, centrality ranking, and community structure. There are three major findings. First, the global major grain trade network has expanded in scale, with a growing emphasis on diversification and balance. During the study period, the United States, Canada, China, and Brazil were the core nodes of the network. Grain-exporting countries were mainly situated in Asia, the Americas, and Europe, and importing countries in Asia, Africa, and Europe. Second, a significant increase in the number of high centrality countries with high export capacity occurred, benefiting from natural advantages such as fertile land and favorable climates. Third, the main global grain trade network is divided into four communities, with the Americas-Europe community being the largest and most widespread. The formation of the community pattern was influenced by geographic proximity, driven by the core exporting countries. Therefore, the world needs to enhance the existing trade model, promote the multi-polarization of the grain trade network, and establish a global vision for the future community. Countries and regions should participate actively in global grain trade security governance and institutional reform, expand trade links with other countries, and optimize import and export policies to reduce trade risks.展开更多
A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled...A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.展开更多
基金the National Natural Science Foundation of China(62203356)Fundamental Research Funds for the Central Universities of China(31020210502002)。
文摘This paper studies the problem of time-varying formation control with finite-time prescribed performance for nonstrict feedback second-order multi-agent systems with unmeasured states and unknown nonlinearities.To eliminate nonlinearities,neural networks are applied to approximate the inherent dynamics of the system.In addition,due to the limitations of the actual working conditions,each follower agent can only obtain the locally measurable partial state information of the leader agent.To address this problem,a neural network state observer based on the leader state information is designed.Then,a finite-time prescribed performance adaptive output feedback control strategy is proposed by restricting the sliding mode surface to a prescribed region,which ensures that the closed-loop system has practical finite-time stability and that formation errors of the multi-agent systems converge to the prescribed performance bound in finite time.Finally,a numerical simulation is provided to demonstrate the practicality and effectiveness of the developed algorithm.
基金the National Key Clinical Specialty Construction Project,No.ZK108000CAMS Innovation Fund for Medical Sciences,No.2021-I2M-C&T-A-001 and No.2022-I2M-C&T-B-012.
文摘BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.
基金supported by the National Research Foundation of Korea Grant funded by the Korean government(MSIP)(No.2018R1A6A1A03025708).
文摘The undesirable dendrite growth induced by non-planar zinc(Zn)deposition and low Coulombic efficiency resulting from severe side reactions have been long-standing challenges for metallic Zn anodes and substantially impede the practical application of rechargeable aqueous Zn metal batteries(ZMBs).Herein,we present a strategy for achieving a high-rate and long-cycle-life Zn metal anode by patterning Zn foil surfaces and endowing a Zn-Indium(Zn-In)interface in the microchannels.The accumulation of electrons in the microchannel and the zincophilicity of the Zn-In interface promote preferential heteroepitaxial Zn deposition in the microchannel region and enhance the tolerance of the electrode at high current densities.Meanwhile,electron aggregation accelerates the dissolution of non-(002)plane Zn atoms on the array surface,thereby directing the subsequent homoepitaxial Zn deposition on the array surface.Consequently,the planar dendrite-free Zn deposition and long-term cycling stability are achieved(5,050 h at 10.0 mA cm^(−2) and 27,000 cycles at 20.0 mA cm^(−2)).Furthermore,a Zn/I_(2) full cell assembled by pairing with such an anode can maintain good stability for 3,500 cycles at 5.0 C,demonstrating the application potential of the as-prepared ZnIn anode for high-performance aqueous ZMBs.
文摘The World Journal of Cardiology published an article written by Kuwahara et al that we take the pleasure to comment on.We focused our attention on venous congestion.In intensive care settings,it is now widely accepted that venous congestion is an important clinical feature worthy of investigation.Evaluating venous Doppler profile abnormalities at multiple sites could suggest adequate treatment and monitor its efficacy.Renal dysfunction could trigger or worsen fluid overload in heart disease,and cardio-renal syndrome is a well-characterized spectrum of disorders describing the complex interactions between heart and kidney diseases.Fluid overload and venous congestion,including renal venous hypertension,are major determinants of acute and chronic renal dysfunction arising in heart disease.Organ congestion from venous hypertension could be involved in the development of organ injury in several clinical situations,such as critical diseases,congestive heart failure,and chronic kidney disease.Ultrasonography and abnormal Doppler flow patterns diagnose clinically significant systemic venous congestion.Cardiologists and nephrologists might use this valuable,noninvasive,bedside diagnostic tool to establish fluid status and guide clinical choices.
基金Project supported by the Special Funds for Basic Operating Expenses of the Centre University of China (Grant No.23ZYJS006)。
文摘Experiments are conducted on the evacuation rate of pedestrians through exits with queued evacuation pattern and random evacuation pattern. The experimental results show that the flow rate of pedestrians is larger with the random evacuation pattern than with the queued evacuation pattern. Therefore, the exit width calculated based on the minimum evacuation clear width for every 100 persons, which is on the assumption that the pedestrians pass through the exit in one queue or several queues, is conservative. The number of people crossing the exit simultaneously is greater in the random evacuation experiments than in the queued evacuation experiments, and the time interval between the front row and rear row of people is shortened in large-exit conditions when pedestrians evacuate randomly. The difference between the flow rate with a queued evacuation pattern and the flow rate with a random evacuation pattern is related to the surplus width of the exit, which is greater than the total width of all accommodated people streams. Two dimensionless quantities are defined to explore this relationship. It is found that the difference in flow rate between the two evacuation patterns is stable at a low level when the surplus width of the exit is no more than 45% of the width of a single pedestrian stream. There is a great difference between the flow rate with the queued evacuation pattern and the flow rate with the random evacuation pattern in a scenario with a larger surplus width of the exit. Meanwhile, the pedestrians crowd extraordinarily at the exit in these conditions as well, since the number of pedestrians who want to evacuate through exit simultaneously greatly exceeds the accommodated level. Therefore, the surplus width of exit should be limited especially in the narrow exit condition, and the relationship between the two dimensionless quantities mentioned above could provide the basis to some extent.
文摘Functional magnetic resonance imaging(fMRI)is a popular tool used to investigate not only how the brain responds to specific stimuli during sensorimotor or cognitive tasks,but also brain activity at rest.The physics beyond this approach is based on the analysis of the blood oxygenation level-dependent signal.
基金Shanxi Scholarship Council of China(2022-141)Fundamental Research Program of Shanxi Province(202203021211096).
文摘Recent research in cross-domain intelligence fault diagnosis of machinery still has some problems,such as relatively ideal speed conditions and sample conditions.In engineering practice,the rotational speed of the machine is often transient and time-varying,which makes the sample annotation increasingly expensive.Meanwhile,the number of samples collected from different health states is often unbalanced.To deal with the above challenges,a complementary-label(CL)adversarial domain adaptation fault diagnosis network(CLADAN)is proposed under time-varying rotational speed and weakly-supervised conditions.In the weakly supervised learning condition,machine prior information is used for sample annotation via cost-friendly complementary label learning.A diagnosticmodel learning strategywith discretized category probabilities is designed to avoidmulti-peak distribution of prediction results.In adversarial training process,we developed virtual adversarial regularization(VAR)strategy,which further enhances the robustness of the model by adding adversarial perturbations in the target domain.Comparative experiments on two case studies validated the superior performance of the proposed method.
基金partially supported by the National Natural Science Foundation of China(52375238)Science and Technology Program of Guangzhou(202201020213,202201020193,202201010399)GZHU-HKUST Joint Research Fund(YH202109).
文摘In time-variant reliability problems,there are a lot of uncertain variables from different sources.Therefore,it is important to consider these uncertainties in engineering.In addition,time-variant reliability problems typically involve a complexmultilevel nested optimization problem,which can result in an enormous amount of computation.To this end,this paper studies the time-variant reliability evaluation of structures with stochastic and bounded uncertainties using a mixed probability and convex set model.In this method,the stochastic process of a limit-state function with mixed uncertain parameters is first discretized and then converted into a timeindependent reliability problem.Further,to solve the double nested optimization problem in hybrid reliability calculation,an efficient iterative scheme is designed in standard uncertainty space to determine the most probable point(MPP).The limit state function is linearized at these points,and an innovative random variable is defined to solve the equivalent static reliability analysis model.The effectiveness of the proposed method is verified by two benchmark numerical examples and a practical engineering problem.
基金supported by the National Science Foundation of China under Grant No.62101467.
文摘Hybrid precoding is considered as a promising low-cost technique for millimeter wave(mm-wave)massive Multi-Input Multi-Output(MIMO)systems.In this work,referring to the time-varying propagation circumstances,with semi-supervised Incremental Learning(IL),we propose an online hybrid beamforming scheme.Firstly,given the constraint of constant modulus on analog beamformer and combiner,we propose a new broadnetwork-based structure for the design model of hybrid beamforming.Compared with the existing network structure,the proposed network structure can achieve better transmission performance and lower complexity.Moreover,to enhance the efficiency of IL further,by combining the semi-supervised graph with IL,we propose a hybrid beamforming scheme based on chunk-by-chunk semi-supervised learning,where only few transmissions are required to calculate the label and all other unlabelled transmissions would also be put into a training data chunk.Unlike the existing single-by-single approach where transmissions during the model update are not taken into the consideration of model update,all transmissions,even the ones during the model update,would make contributions to model update in the proposed method.During the model update,the amount of unlabelled transmissions is very large and they also carry some information,the prediction performance can be enhanced to some extent by these unlabelled channel data.Simulation results demonstrate the spectral efficiency of the proposed method outperforms that of the existing single-by-single approach.Besides,we prove the general complexity of the proposed method is lower than that of the existing approach and give the condition under which its absolute complexity outperforms that of the existing approach.
文摘The purpose of the study was to evaluate the sperm viability of semen infected with PRRSV viral particles, observing the effect of the Virus on the motility of boar sperm. The work was carried out at the FMVZ-BUAP Genetics and Reproduction Laboratory. 5 stallions were used. Each sample contained 1 × 10<sup>6</sup> sperm, the PRRS virus strain was ATCC-VR-2332 (0, 10<sup>2</sup>, 10<sup>4</sup> and 10<sup>6</sup> copies of RNA/mL in triplicate), it was observed daily at the CASA;Hamilton Thorne<sup>®</sup>. Cells with MT (P < 0.05) on days 1, 3, 5, 7 and 10 of evaluation with 201 ± 7.3, 167 ± 10.1, 165 ± 14.6, 134 ± 8.2 and 120 ± 8.8, respectively. The % MP between control and virus concentrations (P ≥ 0.05). The LCV on day 1 and 7 PI at 10X<sup>2</sup> and 10X<sup>6</sup> (P < 0.05) vs control. In the Correlation Matrix, where it is observed that there is a correlation between VSL and VAP, VSL and VCL, VCL and ALH, VAP with ALH. There is a correlation of VSL and ALH, STR and ALH. In this study there were (P ≤ 0.01) in the VCL, in the concentrations (10<sup>2</sup>) 162.81 ± 10.65 and (10<sup>6</sup>) 177.12 ± 5.77 vs 193.04 ± 4.62 of control. This indicates that altering these parameters would be related to fertility and the PRRS virus affects the LCV. Regarding the VSL, it was observed that the sperm infected with viruses 10<sup>2</sup>, 10<sup>4</sup> and 10<sup>6</sup> of 48.00 ± 3.38, 49.88 ± 1.83 and 50.55 ± 2.24 Vs. 56.66 ± 1.68 of control respectively, the control would have greater possibilities of fertilizing the oocyte. In this study, it was found (P ≤ 0.01) in the VAP with 102 of 77.26 ± 5.16, 10<sup>4</sup> with 83.35 ± 2.41 and 10<sup>6</sup> with 81.29 ± 3.14 vs the control with 90.56 ± 2.07. Regarding the ALH there is (P < 0.05) a 10<sup>4</sup> with 8.70 ± .26 and 10<sup>6</sup> with 9.64 ± 0.23 vs control 8.50 ± 0.27. The presence of different concentrations of PRRSV in boar semen induces changes in different types of sperm motility. Infection of ejaculates with the PRRS virus affects sperm motility on days 1, 3, 5, 7, and 10 post-infections.
基金supported by Research project of Shengli Oifield Exploration and Development Research Institute (Grant No.30200018-21-ZC0613-0125)。
文摘For the ultra-high water-cut reservoirs,after long-term water injection exploitation,the physical properties of the reservoir change and the heterogeneity of the reservoir becomes increasingly severe,which further aggravates the spatial difference of the flow field.In this study,the displacement experiments were employed to investigate the variations in core permeability,porosity,and relative permeability after a large amount of water injection.A relative permeability endpoint model was proposed by utilizing the alternating conditional expectation(ACE)transformation to describe the variation in relative permeability based on the experimental data.Based on the time dependent models for permeability and relative permeability,the traditional oil-water two-phase model was improved and discretized using the mimetic finite difference method(MFD).The two cases were launched to confirm the validation of the proposed model.The impact of time-varying physical features on reservoir production performance was studied in a real water flooding reservoir.The experimental results indicate that the overall relative permeability curve shifts to the right as water injection increases.This shift corresponds to a transition towards a more hydrophilic wettability and a decrease in residual oil saturation.The endpoint model demonstrates excellent accuracy and can be applied to time-varying simulations of reservoir physics.The impact of variations in permeability and relative permeability on the reservoir production performance yields two distinct outcomes.The time-varying permeability of the reservoir results in intensified water channeling and poor development effects.On the other hand,the time-varying relative permeability enhances the oil phase seepage capacity,facilitating oil displacement.The comprehensive time-varying behavior is the result of the combined influence of these two parameters,which closely resemble the actual conditions observed in oil field exploitation.The time-varying simulation technique of reservoir physical properties proposed in this paper can continuously and stably characterize the dynamic changes of reservoir physical properties during water drive development.This approach ensures the reliability of the simulation results regarding residual oil distribution.
文摘Pattern matching method is one of the classic classifications of existing online portfolio selection strategies. This article aims to study the key aspects of this method—measurement of similarity and selection of similarity sets, and proposes a Portfolio Selection Method based on Pattern Matching with Dual Information of Direction and Distance (PMDI). By studying different combination methods of indicators such as Euclidean distance, Chebyshev distance, and correlation coefficient, important information such as direction and distance in stock historical price information is extracted, thereby filtering out the similarity set required for pattern matching based investment portfolio selection algorithms. A large number of experiments conducted on two datasets of real stock markets have shown that PMDI outperforms other algorithms in balancing income and risk. Therefore, it is suitable for the financial environment in the real world.
文摘Background: Cardiovascular diseases are the leading cause of death in India, with coronary artery disease (CAD) accounting for a majority of the deaths. There are few large registries on acute coronary syndrome (ACS) from India. Our aim is to study the clinical and epidemiological profile of ACS PATIENTS presenting to our institute, including their angiographic features. Methods: This hospital-based observational, single tertiary care center, prospective study was conducted on patients admitted in the Department of Cardiology at a tertiary care center in Haryana. The study included 400 patients aged greater than 18 years who were admitted with the diagnosis of ACS, and it was carried out for 1 year. The epidemiological profile, clinical history, risk factors, electrocardiogram findings, and angiographic pattern were studied and analyzed with appropriate statistical tools. Results: The mean age of the study population was 55.12 ± 11.78 years. Male and female ratio was 2.4:1. The majority of the patients came from rural background (80%);24% of the patients were illiterate. Smoking was the most common risk factor (51.5%) in our study population followed by hypertension (40%) and diabetes (28%). Unstable angina was the most common type of ACS, which was found in 68.25% of patients. Premature CAD was found in 27.8% of patients and obstructive CAD was found in 63% of patients. Coronary angiography revealed that 39% had single vessel disease (SVD), 23.5% had double vessel disease (DVD), and 27.5% had triple vessel disease (TVD). LAD was more commonly involved, followed by RCA and LCX. Within the first 24 hours, 67% of patients sought medical assistance and only 38.5% received definitive treatment, suggesting a delay in seeking definitive treatment in our study population. Conclusion: The study suggests that unstable angina is the most common form of ACS in the study population, which is mostly of rural background with significant delay in seeking medical help. Smoking is the most common risk factor in the study population.
基金Supported by the Original Exploration Project of National Natural Science Foundation of China(5215000105)Young Teachers Fund for Higher Education Institutions of Huo Yingdong Education Foundation(171043)。
文摘A simulated oil viscosity prediction model is established according to the relationship between simulated oil viscosity and geometric mean value of T2spectrum,and the time-varying law of simulated oil viscosity in porous media is quantitatively characterized by nuclear magnetic resonance(NMR)experiments of high multiple waterflooding.A new NMR wettability index formula is derived based on NMR relaxation theory to quantitatively characterize the time-varying law of rock wettability during waterflooding combined with high-multiple waterflooding experiment in sandstone cores.The remaining oil viscosity in the core is positively correlated with the displacing water multiple.The remaining oil viscosity increases rapidly when the displacing water multiple is low,and increases slowly when the displacing water multiple is high.The variation of remaining oil viscosity is related to the reservoir heterogeneity.The stronger the reservoir homogeneity,the higher the content of heavy components in the remaining oil and the higher the viscosity.The reservoir wettability changes after water injection:the oil-wet reservoir changes into water-wet reservoir,while the water-wet reservoir becomes more hydrophilic;the degree of change enhances with the increase of displacing water multiple.There is a high correlation between the time-varying oil viscosity and the time-varying wettability,and the change of oil viscosity cannot be ignored.The NMR wettability index calculated by considering the change of oil viscosity is more consistent with the tested Amott(spontaneous imbibition)wettability index,which agrees more with the time-varying law of reservoir wettability.
文摘Background: Health challenges that are difficult to manage at primary health centres should be referred to secondary health facilities, and if untreated, to the tertiary hospitals. A good referral should include the patient’s biography, such as age, gender, tribe, religion, occupation, medical history, the reason for the referral, treatments received, and clinical diagnosis. Objectives: To evaluate the referral patterns, indications for referrals, and feto-maternal outcomes for obstetric patients who were referred to the University of Port Harcourt Teaching Hospital. Materials and Methods: A prospective study of patients admitted to the Obstetric unit from January 1, 2021, to December 31, 2022. Data was collected from patients while on admission or clinic visits and recorded in an excel spread sheet. Data was analyzed with the Statistical Package for Social Sciences (SPSS) version 25. Results: Of the 3469 patients were admitted to the obstetric unit, 1476 and 1993 were admitted in 2021 and 2022, respectively. Most (70.35%) of the patients were in the 20-34 years age group, parity 1-4 was the most frequent (66.49%), while 85.39% of patients were booked. 10.46% of the booked patients were referred from other facilities, whereas 89.54% of patients were booked at our facility from the onset. Most common indications of referrals were previous caesarean section (CS) at term (40.09%) and hypertensive disorders of pregnancy (17.59%). The outcome for 2021 indicated 17 maternal deaths, 132 fetal deaths and 1010 live births, giving maternal mortality ratio (MMR) as 1810.44 per 100,000 live births and perinatal mortality ratio (PMR) of 130.7 per 1000 births respectively. In 2022, there were 17 maternal deaths, 130 fetal deaths and 1297 deliveries, giving a MMR of 1399 per 100,000 live births and a PMR of 100.2 per 1000 births. Conclusion: The pattern of referral among obstetric patients in this study shows that a lot of the patients do not get adequate care at the lower cadre of the referral system, hence adequate facilities should be made available in primary and secondary health centres to tackle obstetric emergencies.
基金supported by the National Natural Science Foundation of China(Grant Numbers:U22A20234,42277170)the Key Research and Development Project of Hubei Province(Grant Number:2020BCB073).
文摘To analyze the effects of a time-varying viscosity on the penetration length of grouting,in this study cement slur-ries with varying water-cement ratios have been investigated using the Bingham’sfluidflow equation and a dis-crete element method.Afluid-solid coupling numerical model has been introduced accordingly,and its accuracy has been validated through comparison of theoretical and numerical solutions.For different fracture forms(a single fracture,a branch fracture,and a fracture network),the influence of the time-varying viscosity on the slurry length range has been investigated,considering the change in the fracture aperture.The results show that under different fracture forms and the same grouting process conditions,the influence of the time-varying viscosity on the seepage length is 0.350 m.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.32271293 and 11875076)。
文摘Positional information encoded in spatial concentration patterns is crucial for the development of multicellular organisms.However,it is still unclear how such information is affected by the physically dissipative diffusion process.Here we study one-dimensional patterning systems with analytical derivation and numerical simulations.We find that the diffusion constant of the patterning molecules exhibits a nonmonotonic effect on the readout of the positional information from the concentration patterns.Specifically,there exists an optimal diffusion constant that maximizes the positional information.Moreover,we find that the energy dissipation due to the physical diffusion imposes a fundamental upper limit on the positional information.
基金funded by the National Natural Science Foundation of China(42271313)the Chinese Academy of Agricultural Sciences Innovation Project(CAAS-ASTIP2021-AII)the Central Public-interest Scientific Institution Basal Research Fund,China(JBYW-AII-2022-06,JBYWAII-2022-40)。
文摘The complex and volatile international landscape has significantly impacted global grain supply security. This study uses a complex network analysis model to examine the evolution and trends of the global major grain trade from 1990 to 2020, focusing on network topology, centrality ranking, and community structure. There are three major findings. First, the global major grain trade network has expanded in scale, with a growing emphasis on diversification and balance. During the study period, the United States, Canada, China, and Brazil were the core nodes of the network. Grain-exporting countries were mainly situated in Asia, the Americas, and Europe, and importing countries in Asia, Africa, and Europe. Second, a significant increase in the number of high centrality countries with high export capacity occurred, benefiting from natural advantages such as fertile land and favorable climates. Third, the main global grain trade network is divided into four communities, with the Americas-Europe community being the largest and most widespread. The formation of the community pattern was influenced by geographic proximity, driven by the core exporting countries. Therefore, the world needs to enhance the existing trade model, promote the multi-polarization of the grain trade network, and establish a global vision for the future community. Countries and regions should participate actively in global grain trade security governance and institutional reform, expand trade links with other countries, and optimize import and export policies to reduce trade risks.
基金supported by the National Natural Science Foundation of China(Nos.31972929 and 62231025)the Research Program of Shanghai Science and Technology Committee(Nos.21140901300 and 20DZ2220400)+3 种基金the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX0767)the Interdisciplinary Program of Shanghai Jiao Tong University(Nos.YG2021ZD22 and YG2023LC04)the Foundation of National Center for Translational Medicine(Shanghai)SHU Branch(No.SUITM-2023008)the Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYJC202108).
文摘A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.