Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3...Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.展开更多
Transfer learning is the predominant method for adapting pre-trained models on another task to new domains while preserving their internal architectures and augmenting them with requisite layers in Deep Neural Network...Transfer learning is the predominant method for adapting pre-trained models on another task to new domains while preserving their internal architectures and augmenting them with requisite layers in Deep Neural Network models.Training intricate pre-trained models on a sizable dataset requires significant resources to fine-tune hyperparameters carefully.Most existing initialization methods mainly focus on gradient flow-related problems,such as gradient vanishing or exploding,or other existing approaches that require extra models that do not consider our setting,which is more practical.To address these problems,we suggest employing gradient-free heuristic methods to initialize the weights of the final new-added fully connected layer in neural networks froma small set of training data with fewer classes.The approach relies on partitioning the output values from pre-trained models for a small set into two separate intervals determined by the targets.This process is framed as an optimization problem for each output neuron and class.The optimization selects the highest values as weights,considering their direction towards the respective classes.Furthermore,empirical 145 experiments involve a variety of neural networkmodels tested acrossmultiple benchmarks and domains,occasionally yielding accuracies comparable to those achieved with gradient descent methods by using only small subsets.展开更多
BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant m...BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant mortality.AIM To investigate the effects of frailty on mortality after liver transplantation.METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score.Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.RESULTS Of 82.7%frail patients,42.7%were severely frail and 40%were moderately frail(P<0.001)at the time of transplantation.Compared with non-frail patients,post-transplant mortality in frail patients was significantly higher at 12 months[odds ratio(OR)=1.94,P=0.02].Secondary analysis of the data revealed that liver grafts from donation after circulatory death(DCD)were more likely to be associated with frail patients at transplant(OR=1.86,P<0.001).Furthermore,a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant(OR=0.65,P=0.03).CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation,and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.展开更多
While the Coronavirus Disease 2019(COVID-19)pandemic continues to threaten public health and safety,every state has strategically reopened the business in the United States.It is urgent to evaluate the effect of reope...While the Coronavirus Disease 2019(COVID-19)pandemic continues to threaten public health and safety,every state has strategically reopened the business in the United States.It is urgent to evaluate the effect of reopening policies on the COVID-19 pandemic to help with the decision-making on the control measures and medical resource allocations.In this study,a novel SEIR model was developed to evaluate the effect of reopening policies based on the real-world reported COVID-19 data in Texas.The earlier reported data before the reopening were used to develop the SEIR model;data after the reopening were used for evaluation.The simulation results show that if continuing the“stay-at-home order”without reopening the business,the COVID-19 pandemic could end in December 2020 in Texas.On the other hand,the pandemic could be controlled similarly as the case of noreopening only if the contact rate was low and additional high magnitude of control measures could be implemented.If the control measures are only slightly enhanced after reopening,it could flatten the curve of the COVID-19 epidemic with reduced numbers of infections and deaths,but it might make the epidemic last longer.Based on the reported data up to July 2020 in Texas,the real-world epidemic pattern is between the cases of the low and high magnitude of control measures with a medium risk of contact rate after reopening.In this case,the pandemic might last until summer 2021 to February 2022 with a total of 4-10 million infected cases and 20,080e58,604 deaths.展开更多
There are a few statistics testing the homogeneity of odds ratios across strata. Asymptotic statistics lose their power in the “sparse-data” setting. Both asymptotic statistics and exact tests have low power when th...There are a few statistics testing the homogeneity of odds ratios across strata. Asymptotic statistics lose their power in the “sparse-data” setting. Both asymptotic statistics and exact tests have low power when the sample sizes are small. We created a set of U statistics and compared them with some existing statistics in testing homogeneity of OR at different data settings. We evaluated their performance in terms of the empirical size and power via Monto Carlo simulations. Our results showed that two of the U-statistics under our study had higher power for testing homogeneity of odds ratios for 2 by 2 contingency tables. The application of the tests was illustrated in two real examples.展开更多
Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease...Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.展开更多
Bordetella pertussis(B.pertussis)is the causative agent of pertussis,also referenced as whooping cough.Although pertussis has been appropriately controlled by routine immunization of infants,it has experienced a resur...Bordetella pertussis(B.pertussis)is the causative agent of pertussis,also referenced as whooping cough.Although pertussis has been appropriately controlled by routine immunization of infants,it has experienced a resurgence since the beginning of the 21st century.Given that elucidating the immune response to pertussis is a crucial factor to improve therapeutic and preventive treatments,we re-analyzed a time course microarray dataset of B.pertussis infection by applying a newly developed dynamic data analysis pipeline.Our results indicate that the immune response to B.pertussis is highly dynamic and heterologous across different organs during infection.Th1 and Th17 cells,which are two critical types of T helper cell populations in the immune response to B.pertussis,and follicular T helper cells(TFHs),which are also essential for generating antibodies,might be generated at different time points and distinct locations after infection.This phenomenon may indicate that different lymphoid organs may have their unique functions during infection.These findings provide a better understanding of the basic immunology of bacterial infection,which may provide valuable insights for the improvement of pertussis vaccine design in the future.展开更多
Gut microbiota-derived metabolites influence host physiology and pathology,where short-chain fatty acids(SCFAs)are the main class of gut microbiota-derived metabolites.[1]SCFAs are fatty acids containing 1 to 6 carbon...Gut microbiota-derived metabolites influence host physiology and pathology,where short-chain fatty acids(SCFAs)are the main class of gut microbiota-derived metabolites.[1]SCFAs are fatty acids containing 1 to 6 carbon atoms,including acetate,propionate,butyrate,and pentanoate,which provide 6%to 10%of the body’s total daily energy and 60%to 70%of the colonic epithelial energy needed.[2]Anaerobic bacteria principally generate the SCFAs[1]in the intestine.Once produced,SCFAs are mainly absorbed in the colon(90%–95%),reach circulation,and play roles for distal organs and tissues.[2]展开更多
The scientific foundation of a modern clinical trial is randomization–each patient is randomized to a treatment group,and statistical comparisons are made between treatment groups.Because the study units are individu...The scientific foundation of a modern clinical trial is randomization–each patient is randomized to a treatment group,and statistical comparisons are made between treatment groups.Because the study units are individual patients,this‘one patient,one vote’principle needs to be fol-lowed–bothinstudydesignandindataanalysis.Fromthephysicians’pointofview,eachpatient is equally important,and they need to be treated equally in data analysis.It is critical that statisti-cal analysis should respect design and study design is based on randomization.Hence from both statistical and medical points of view,data analysis needs to follow this‘one patient,one vote’principle.Under ICH E9(R1),five strategies are recommended to establish‘estimand’.This paper discusses how to implement these strategies using the‘one patient,one vote’principle.展开更多
This article studies the estimation and statistical inference problems of semi-functional partially linear regression models when the covariates in the linear part are measured with additive error. To obtain the estim...This article studies the estimation and statistical inference problems of semi-functional partially linear regression models when the covariates in the linear part are measured with additive error. To obtain the estimation of the parametric component, a corrected profile least-squares based estimation procedure is developed. Asymptotic properties of the proposed estimators are established under some mild assumptions. To test hypothesis on the parametric part, the authors propose a novel test statistic based on the difference between the corrected residual sums of squares under the null and alternative hypotheses, and show that its limiting distribution is a weighted sum of independent standard χ12. Finally, the authors illustrate the finite sample performance of the methods with some simulation studies and a real data application.展开更多
The genus Streptococcus,a gram-positive bacterium,con-tains species associated with immune activation at morbid outcomes,including scarlet fever,endocarditis,meningitis,and rheumatic fever.In both stool and saliva,the...The genus Streptococcus,a gram-positive bacterium,con-tains species associated with immune activation at morbid outcomes,including scarlet fever,endocarditis,meningitis,and rheumatic fever.In both stool and saliva,there is a pos-itive correlation between Streptococcus abundance and Sjogren’s syndrome(SS)and systemic lupus erythematosus(SLE).展开更多
Objective To investigate the differences in delivery mode,daily dose,and catheter tip location in pediatric patients using intrathecal baclofen(ITB)pumps with spasticity plus dystonia versus spasticity alone.Methods A...Objective To investigate the differences in delivery mode,daily dose,and catheter tip location in pediatric patients using intrathecal baclofen(ITB)pumps with spasticity plus dystonia versus spasticity alone.Methods A single-center,cross-sectional study was performed by collecting retrospective data from electronic medical records.Demographic and diagnostic information was obtained,comparing patients with spasticity with or without dystonia.The data were analyzed for group differences using a two-tailed Student’s t-test.Categorical data were analyzed for group differences using Pearson’s χ^(2) test.Results A total of 137 patients met the criteria.The majority(114)had spasticity plus dystonia whereas only 23 were documented as spasticity alone.Simple continuous dosing was the most common delivery mode,but flex dosing was used more than twice as frequently with spasticity plus dystonia compared with spasticity alone(42%vs 17%).Patients with spasticity plus dystonia also had more rostral catheter tip locations.Conclusions While it has been discussed anecdotally,this study confirms the supposition that patients with spasticity plus dystonia have increased dose requirements when compared with those with spasticity alone.Although there are no clear standards of care when managing these patients,they are often on higher daily dosages,are more likely to require flexed dosing method,and have higher catheter placements.Still,there are few studies that demonstrate improvements in dystonia with the use of ITB.In general,these patients would benefit from the development of universal standardizations as well as the confirmation that this is an appropriate treatment.展开更多
Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The fir...Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event- related power between CNAβ+ and CNAβ−. Methods: Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 ampli-tude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Simi-larly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ partici-pants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69;P = 0.003) and 2-back (r = − 0.69;P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.展开更多
文摘Plasmodium (P.) falciparum is a pathogen that causes severe forms of malaria. Protein interactions have been shown to occur between P. falciparum and human erythrocytes in human blood. The Band 3 Anion Transporter (B3AT) protein is considered the main invasive pathway for the parasite in erythrocytes that causes clinical symptoms for malaria in humans. The interactions between P. falciparum parasites and erythrocytes along this receptor have previously been explored. Short linear motifs (SLIMs) are short linear mediator sequences that involve several biological processes, acting as mediators of protein interactions identifiable by computational tools such as SLiMFinder. For a given protein, the identification of SLIMs allows predicting its interactors. Using the SLIMs approach, protein-protein interaction network analyses between P. falciparum and its human host, were used to identify a tryptophan-rich protein, A5K5E5_PLAVS as an essential interactor of B3AT. To better understand the interaction mechanism, a guided protein-protein docking approach based on SLIM motifs was performed for human B3AT and A5K5E5_PLAVS. The highlights of this important interaction between P. falciparum and its human host have the potential to pave the way to identify new therapeutic candidates.
基金supported by the BK21 FOUR project(AI-driven Convergence Software Education Research Program)funded by the Ministry of Education,School of Computer Science and Engineering,Kyungpook National University,Republic of Korea(4120240214871)supported by the New Faculty Start Up Fund from LSU Health Sciences New Orleans,LA,USA.
文摘Transfer learning is the predominant method for adapting pre-trained models on another task to new domains while preserving their internal architectures and augmenting them with requisite layers in Deep Neural Network models.Training intricate pre-trained models on a sizable dataset requires significant resources to fine-tune hyperparameters carefully.Most existing initialization methods mainly focus on gradient flow-related problems,such as gradient vanishing or exploding,or other existing approaches that require extra models that do not consider our setting,which is more practical.To address these problems,we suggest employing gradient-free heuristic methods to initialize the weights of the final new-added fully connected layer in neural networks froma small set of training data with fewer classes.The approach relies on partitioning the output values from pre-trained models for a small set into two separate intervals determined by the targets.This process is framed as an optimization problem for each output neuron and class.The optimization selects the highest values as weights,considering their direction towards the respective classes.Furthermore,empirical 145 experiments involve a variety of neural networkmodels tested acrossmultiple benchmarks and domains,occasionally yielding accuracies comparable to those achieved with gradient descent methods by using only small subsets.
文摘BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia,there is an increased risk of frailty as measured by functional impairment,making frailty a vital predictor of post-transplant mortality.AIM To investigate the effects of frailty on mortality after liver transplantation.METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score.Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.RESULTS Of 82.7%frail patients,42.7%were severely frail and 40%were moderately frail(P<0.001)at the time of transplantation.Compared with non-frail patients,post-transplant mortality in frail patients was significantly higher at 12 months[odds ratio(OR)=1.94,P=0.02].Secondary analysis of the data revealed that liver grafts from donation after circulatory death(DCD)were more likely to be associated with frail patients at transplant(OR=1.86,P<0.001).Furthermore,a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant(OR=0.65,P=0.03).CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation,and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.
基金This project is partially supported by NIH grant R01 AI087135 and the Center for Big Data in Health Sciences(CBD-HS)at School of Public Health,The University of Texas Health Science Center at Houston,UTHealth.
文摘While the Coronavirus Disease 2019(COVID-19)pandemic continues to threaten public health and safety,every state has strategically reopened the business in the United States.It is urgent to evaluate the effect of reopening policies on the COVID-19 pandemic to help with the decision-making on the control measures and medical resource allocations.In this study,a novel SEIR model was developed to evaluate the effect of reopening policies based on the real-world reported COVID-19 data in Texas.The earlier reported data before the reopening were used to develop the SEIR model;data after the reopening were used for evaluation.The simulation results show that if continuing the“stay-at-home order”without reopening the business,the COVID-19 pandemic could end in December 2020 in Texas.On the other hand,the pandemic could be controlled similarly as the case of noreopening only if the contact rate was low and additional high magnitude of control measures could be implemented.If the control measures are only slightly enhanced after reopening,it could flatten the curve of the COVID-19 epidemic with reduced numbers of infections and deaths,but it might make the epidemic last longer.Based on the reported data up to July 2020 in Texas,the real-world epidemic pattern is between the cases of the low and high magnitude of control measures with a medium risk of contact rate after reopening.In this case,the pandemic might last until summer 2021 to February 2022 with a total of 4-10 million infected cases and 20,080e58,604 deaths.
文摘There are a few statistics testing the homogeneity of odds ratios across strata. Asymptotic statistics lose their power in the “sparse-data” setting. Both asymptotic statistics and exact tests have low power when the sample sizes are small. We created a set of U statistics and compared them with some existing statistics in testing homogeneity of OR at different data settings. We evaluated their performance in terms of the empirical size and power via Monto Carlo simulations. Our results showed that two of the U-statistics under our study had higher power for testing homogeneity of odds ratios for 2 by 2 contingency tables. The application of the tests was illustrated in two real examples.
文摘Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.
基金This work is partially supported by NIH/NIAID grant RO1 AI087135CAA is supported by NIH/NIAID grant K24 AI114818.
文摘Bordetella pertussis(B.pertussis)is the causative agent of pertussis,also referenced as whooping cough.Although pertussis has been appropriately controlled by routine immunization of infants,it has experienced a resurgence since the beginning of the 21st century.Given that elucidating the immune response to pertussis is a crucial factor to improve therapeutic and preventive treatments,we re-analyzed a time course microarray dataset of B.pertussis infection by applying a newly developed dynamic data analysis pipeline.Our results indicate that the immune response to B.pertussis is highly dynamic and heterologous across different organs during infection.Th1 and Th17 cells,which are two critical types of T helper cell populations in the immune response to B.pertussis,and follicular T helper cells(TFHs),which are also essential for generating antibodies,might be generated at different time points and distinct locations after infection.This phenomenon may indicate that different lymphoid organs may have their unique functions during infection.These findings provide a better understanding of the basic immunology of bacterial infection,which may provide valuable insights for the improvement of pertussis vaccine design in the future.
基金supported by the National Key R&D Program of China(No.2020YFC2005000)the National Science Foundation of China(No.82100775).
文摘Gut microbiota-derived metabolites influence host physiology and pathology,where short-chain fatty acids(SCFAs)are the main class of gut microbiota-derived metabolites.[1]SCFAs are fatty acids containing 1 to 6 carbon atoms,including acetate,propionate,butyrate,and pentanoate,which provide 6%to 10%of the body’s total daily energy and 60%to 70%of the colonic epithelial energy needed.[2]Anaerobic bacteria principally generate the SCFAs[1]in the intestine.Once produced,SCFAs are mainly absorbed in the colon(90%–95%),reach circulation,and play roles for distal organs and tissues.[2]
文摘The scientific foundation of a modern clinical trial is randomization–each patient is randomized to a treatment group,and statistical comparisons are made between treatment groups.Because the study units are individual patients,this‘one patient,one vote’principle needs to be fol-lowed–bothinstudydesignandindataanalysis.Fromthephysicians’pointofview,eachpatient is equally important,and they need to be treated equally in data analysis.It is critical that statisti-cal analysis should respect design and study design is based on randomization.Hence from both statistical and medical points of view,data analysis needs to follow this‘one patient,one vote’principle.Under ICH E9(R1),five strategies are recommended to establish‘estimand’.This paper discusses how to implement these strategies using the‘one patient,one vote’principle.
基金supported by National Natural Science Foundation of China under Grant Nos.11571112,11501372,11571148,11471160Program of Shanghai Subject Chief Scientist(14XD1401600)+2 种基金the 111 Project of China(B14019)Project of National Social Science Fund of China(15BTJ027)Research Innovation Program for ECNU Graduates(ykc17083)
文摘This article studies the estimation and statistical inference problems of semi-functional partially linear regression models when the covariates in the linear part are measured with additive error. To obtain the estimation of the parametric component, a corrected profile least-squares based estimation procedure is developed. Asymptotic properties of the proposed estimators are established under some mild assumptions. To test hypothesis on the parametric part, the authors propose a novel test statistic based on the difference between the corrected residual sums of squares under the null and alternative hypotheses, and show that its limiting distribution is a weighted sum of independent standard χ12. Finally, the authors illustrate the finite sample performance of the methods with some simulation studies and a real data application.
基金supported by the National Institutes of Health,Bethesda,MD[No.5P50 AR070591(J.P.B.),5R21 AR071106(J.P.B.and C.D.L.),AR-4-2220(J.P.B.),P30AR073750(JAJ),UM1AI144292(JAJ)].
文摘The genus Streptococcus,a gram-positive bacterium,con-tains species associated with immune activation at morbid outcomes,including scarlet fever,endocarditis,meningitis,and rheumatic fever.In both stool and saliva,there is a pos-itive correlation between Streptococcus abundance and Sjogren’s syndrome(SS)and systemic lupus erythematosus(SLE).
文摘Objective To investigate the differences in delivery mode,daily dose,and catheter tip location in pediatric patients using intrathecal baclofen(ITB)pumps with spasticity plus dystonia versus spasticity alone.Methods A single-center,cross-sectional study was performed by collecting retrospective data from electronic medical records.Demographic and diagnostic information was obtained,comparing patients with spasticity with or without dystonia.The data were analyzed for group differences using a two-tailed Student’s t-test.Categorical data were analyzed for group differences using Pearson’s χ^(2) test.Results A total of 137 patients met the criteria.The majority(114)had spasticity plus dystonia whereas only 23 were documented as spasticity alone.Simple continuous dosing was the most common delivery mode,but flex dosing was used more than twice as frequently with spasticity plus dystonia compared with spasticity alone(42%vs 17%).Patients with spasticity plus dystonia also had more rostral catheter tip locations.Conclusions While it has been discussed anecdotally,this study confirms the supposition that patients with spasticity plus dystonia have increased dose requirements when compared with those with spasticity alone.Although there are no clear standards of care when managing these patients,they are often on higher daily dosages,are more likely to require flexed dosing method,and have higher catheter placements.Still,there are few studies that demonstrate improvements in dystonia with the use of ITB.In general,these patients would benefit from the development of universal standardizations as well as the confirmation that this is an appropriate treatment.
基金the National Institute on Aging of the National Institutes of Health under Award Number K01 AG058785This study was supported in part by a pilot grant of the KU Alzheimer Disease Center(P30 AG035982).
文摘Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event- related power between CNAβ+ and CNAβ−. Methods: Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 ampli-tude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Simi-larly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ partici-pants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69;P = 0.003) and 2-back (r = − 0.69;P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.
