Browsing by Subject "Linear Models"
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Item Open Access A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.(Journal of neurotrauma, 2012-09) Wilson, Jefferson R; Grossman, Robert G; Frankowski, Ralph F; Kiss, Alexander; Davis, Aileen M; Kulkarni, Abhaya V; Harrop, James S; Aarabi, Bizhan; Vaccaro, Alexander; Tator, Charles H; Dvorak, Marcel; Shaffrey, Christopher I; Harkema, Susan; Guest, James D; Fehlings, Michael GTo improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score >50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families.Item Open Access A latent factor linear mixed model for high-dimensional longitudinal data analysis.(Statistics in medicine, 2013-10) An, Xinming; Yang, Qing; Bentler, Peter MHigh-dimensional longitudinal data involving latent variables such as depression and anxiety that cannot be quantified directly are often encountered in biomedical and social sciences. Multiple responses are used to characterize these latent quantities, and repeated measures are collected to capture their trends over time. Furthermore, substantive research questions may concern issues such as interrelated trends among latent variables that can only be addressed by modeling them jointly. Although statistical analysis of univariate longitudinal data has been well developed, methods for modeling multivariate high-dimensional longitudinal data are still under development. In this paper, we propose a latent factor linear mixed model (LFLMM) for analyzing this type of data. This model is a combination of the factor analysis and multivariate linear mixed models. Under this modeling framework, we reduced the high-dimensional responses to low-dimensional latent factors by the factor analysis model, and then we used the multivariate linear mixed model to study the longitudinal trends of these latent factors. We developed an expectation-maximization algorithm to estimate the model. We used simulation studies to investigate the computational properties of the expectation-maximization algorithm and compare the LFLMM model with other approaches for high-dimensional longitudinal data analysis. We used a real data example to illustrate the practical usefulness of the model.Item Open Access A tutorial on Bayesian multi-model linear regression with BAS and JASP.(Behavior research methods, 2021-12) Bergh, Don van den; Clyde, Merlise A; Gupta, Akash R Komarlu Narendra; de Jong, Tim; Gronau, Quentin F; Marsman, Maarten; Ly, Alexander; Wagenmakers, Eric-JanLinear regression analyses commonly involve two consecutive stages of statistical inquiry. In the first stage, a single 'best' model is defined by a specific selection of relevant predictors; in the second stage, the regression coefficients of the winning model are used for prediction and for inference concerning the importance of the predictors. However, such second-stage inference ignores the model uncertainty from the first stage, resulting in overconfident parameter estimates that generalize poorly. These drawbacks can be overcome by model averaging, a technique that retains all models for inference, weighting each model's contribution by its posterior probability. Although conceptually straightforward, model averaging is rarely used in applied research, possibly due to the lack of easily accessible software. To bridge the gap between theory and practice, we provide a tutorial on linear regression using Bayesian model averaging in JASP, based on the BAS package in R. Firstly, we provide theoretical background on linear regression, Bayesian inference, and Bayesian model averaging. Secondly, we demonstrate the method on an example data set from the World Happiness Report. Lastly, we discuss limitations of model averaging and directions for dealing with violations of model assumptions.Item Open Access Artificial Intelligence Models Predict Operative Versus Nonoperative Management of Patients with Adult Spinal Deformity with 86% Accuracy.(World neurosurgery, 2020-09) Durand, Wesley M; Daniels, Alan H; Hamilton, David K; Passias, Peter; Kim, Han Jo; Protopsaltis, Themistocles; LaFage, Virginie; Smith, Justin S; Shaffrey, Christopher; Gupta, Munish; Klineberg, Eric; Schwab, Frank; Burton, Doug; Bess, Shay; Ames, Christopher; Hart, Robert; International Spine Study GroupObjective
Patients with ASD show complex and highly variable disease. The decision to manage patients operatively is largely subjective and varies based on surgeon training and experience. We sought to develop models capable of accurately discriminating between patients receiving operative versus nonoperative treatment based only on baseline radiographic and clinical data at enrollment.Methods
This study was a retrospective analysis of a multicenter consecutive cohort of patients with ASD. A total of 1503 patients were included, divided in a 70:30 split for training and testing. Patients receiving operative treatment were defined as those undergoing surgery up to 1 year after their baseline visit. Potential predictors included available demographics, past medical history, patient-reported outcome measures, and premeasured radiographic parameters from anteroposterior and lateral films. In total, 321 potential predictors were included. Random forest, elastic net regression, logistic regression, and support vector machines (SVMs) with radial and linear kernels were trained.Results
Of patients in the training and testing sets, 69.0% (n = 727) and 69.1% (n = 311), respectively, received operative management. On evaluation with the testing dataset, performance for SVM linear (area under the curve =0.910), elastic net (0.913), and SVM radial (0.914) models was excellent, and the logistic regression (0.896) and random forest (0.830) models performed very well for predicting operative management of patients with ASD. The SVM linear model showed 86% accuracy.Conclusions
This study developed models showing excellent discrimination (area under the curve >0.9) between patients receiving operative versus nonoperative management, based solely on baseline study enrollment values. Future investigations may evaluate the implementation of such models for decision support in the clinical setting.Item Open Access Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events.(Circ Cardiovasc Genet, 2010-04) Shah, Svati H; Bain, James R; Muehlbauer, Michael J; Stevens, Robert D; Crosslin, David R; Haynes, Carol; Dungan, Jennifer; Newby, L Kristin; Hauser, Elizabeth R; Ginsburg, Geoffrey S; Newgard, Christopher B; Kraus, William EBACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01). CONCLUSIONS: Metabolite profiles are associated with CAD and subsequent cardiovascular events.Item Open Access Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.(Oncotarget, 2016-12) Zhou, Fei; Qiu, Li-Xin; Cheng, Lei; Wang, Meng-Yun; Li, Jin; Sun, Meng-Hong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiInterleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27-5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03-1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54-0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46-0.89 and adjusted OR = 0.38, 95% CI = 0.17-0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.Item Open Access Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.(Health and quality of life outcomes, 2018-11-21) Yeoh, Yen Shing; Koh, Gerald Choon-Huat; Tan, Chuen Seng; Lee, Kim En; Tu, Tian Ming; Singh, Rajinder; Chang, Hui Meng; De Silva, Deidre A; Ng, Yee Sien; Ang, Yan Hoon; Yap, Philip; Chew, Effie; Merchant, Reshma Aziz; Yeo, Tseng Tsai; Chou, Ning; Venketasubramanian, N; Young, Sherry H; Hoenig, Helen; Matchar, David Bruce; Luo, NanBackground
Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke.Methods
Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions.Results
All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized β = - 0.111; 12-month standardized β = - 0.109) and mRS (3-month standardized β = - 0.122; 12-month standardized β = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D.Conclusions
HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.Item Open Access Chimpanzees and bonobos exhibit divergent spatial memory development.(Dev Sci, 2012-11) Rosati, Alexandra G; Hare, BrianSpatial cognition and memory are critical cognitive skills underlying foraging behaviors for all primates. While the emergence of these skills has been the focus of much research on human children, little is known about ontogenetic patterns shaping spatial cognition in other species. Comparative developmental studies of nonhuman apes can illuminate which aspects of human spatial development are shared with other primates, versus which aspects are unique to our lineage. Here we present three studies examining spatial memory development in our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (P. paniscus). We first compared memory in a naturalistic foraging task where apes had to recall the location of resources hidden in a large outdoor enclosure with a variety of landmarks (Studies 1 and 2). We then compared older apes using a matched memory choice paradigm (Study 3). We found that chimpanzees exhibited more accurate spatial memory than bonobos across contexts, supporting predictions from these species' different feeding ecologies. Furthermore, chimpanzees - but not bonobos - showed developmental improvements in spatial memory, indicating that bonobos exhibit cognitive paedomorphism (delays in developmental timing) in their spatial abilities relative to chimpanzees. Together, these results indicate that the development of spatial memory may differ even between closely related species. Moreover, changes in the spatial domain can emerge during nonhuman ape ontogeny, much like some changes seen in human children.Item Open Access Complications, revision fusions, readmissions, and utilization over a 1-year period after bone morphogenetic protein use during primary cervical spine fusions.(The spine journal : official journal of the North American Spine Society, 2014-09) Goode, Adam P; Richardson, William J; Schectman, Robin M; Carey, Timothy SBackground context
Nationwide estimates examining bone morphogenetic protein (BMP) use with cervical spine fusions have been limited to perioperative outcomes.Purpose
To determine the 1-year risk of complications, cervical revision fusions, hospital readmissions, and health care services utilization.Study design
A retrospective cohort study from 2002 to 2009 using a nationwide claims database.Patient sample
There were 61,937 primary cervical spine fusions of which 1,677 received BMP.Outcome measures
Complications, revision fusions, 30-day hospital readmission, and health care utilization.Methods
Data for these analyses come from the Thomson Reuters MarketScan Commercial Claims and Encounters Database 2010. Patients were aged 18 to 64 years, receiving and not receiving BMP with a primary (C2-C7) cervical spine fusion. All outcomes were defined by International Classification of Diseases, 9th edition Clinical Modification and Current Procedural and Terminology, 4th edition codes. Complications were analyzed as any complication and stratified by nervous system, wound, and dysphagia or hoarseness. Cervical revision fusions were determined in the 1-year follow-up. Hospital readmission discharge records defined 30-day hospital readmission and reason for the readmission. The utilization of at least one health care service of cervical spine imaging, epidural usage or rehabilitation service was examined. Poisson regression models were used to estimate the relative risk and 95% confidence interval (CI). Linear regression was used to determine the time to hospital readmission. Results were stratified by anterior or posterior and circumferential approaches.Results
Patients receiving BMP were 29% more likely to have a complication (adjusted relative risk [aRR]=1.29 [95% CI, 1.14-1.46]) and a nervous system complication (aRR=1.42 [95% CI, 1.10-1.83]). Cervical revision fusions were more likely among patients receiving BMP (aRR=1.69 [95% CI, 1.35-2.13]). The risk of 30-day readmission was greater with BMP use (aRR=1.37 [95% CI, 1.07-1.73]) and readmission occurred 27.4% sooner on an average. Patients receiving BMP were more likely to receive computed tomography scans (aRR=1.34 [95% CI, 1.06-1.70]) and epidurals with anterior surgical approaches (aRR=1.29 [95% CI, 1.00-1.65]).Conclusions
These findings question both the safety and effectiveness of off-label BMP use in primary cervical spine fusions.Item Open Access Credit scores, cardiovascular disease risk, and human capital.(Proc Natl Acad Sci U S A, 2014-12-02) Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie ECredit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.Item Open Access Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma.(BMC Cancer, 2010-05-19) DeLorenze, Gerald N; McCoy, Lucie; Tsai, Ai-Lin; Quesenberry, Charles P; Rice, Terri; Il'yasova, Dora; Wrensch, MargaretBACKGROUND: Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. METHODS: Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects. RESULTS: Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n=748) to self-reported cases only (n=450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases. CONCLUSIONS: The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.Item Open Access Deficiency of α-1-antitrypsin influences systemic iron homeostasis.(Int J Chron Obstruct Pulmon Dis, 2013) Ghio, Andrew J; Soukup, Joleen M; Richards, Judy H; Fischer, Bernard M; Voynow, Judith A; Schmechel, Donald EThere is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals) were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP). Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES). Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative) relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively) with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Item Open Access Dietary Patterns Associated with Cognitive Function among the Older People in Underdeveloped Regions: Finding from the NCDFaC Study.(Nutrients, 2018-04-09) Yin, Zhaoxue; Chen, Jing; Zhang, Jian; Ren, Zeping; Dong, Kui; Kraus, Virginia B; Wang, Zhuoqun; Zhang, Mei; Zhai, Yi; Song, Pengkun; Zhao, Yanfang; Pang, Shaojie; Mi, Shengquan; Zhao, WenhuaAlthough dietary patterns are crucial to cognitive function, associations of dietary patterns with cognitive function have not yet been fully understood. This cross-sectional study explored dietary patterns associated with cognitive function among the older adults in underdeveloped regions, using 1504 community-dwelling older adults aged 60 and over. Diet was assessed using a food frequency questionnaire and 24-h dietary recall. Factor analysis was used to extract dietary patterns. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Two dietary patterns, a "mushroom, vegetable, and fruits" (MVF) pattern and a "meat and soybean products" (MS) pattern, were identified. The MVF pattern, characterized by high consumption of mushrooms, vegetables, and fruits was significantly positively associated with cognitive function (p < 0.05), with an odds ratio of (95% CIs) 0.60 (0.38, 0.94) for cognitive impairment and β (95% CIs) 0.15 (0.02, 0.29) for -log (31-MMSE score). The MS pattern, characterized by high consumption of soybean products and meat, was also associated with better cognitive function, with an odds ratio of 0.47 (95% CIs 0.30, 0.74) for cognitive impairment and β (95% CIs) 0.34 (0.21, 0.47) for -log (31-MMSE score). Our results suggested that both the MVF and MS patterns were positively associated with better cognitive function among older adults in underdeveloped regions.Item Open Access Early Patient-Reported Outcomes Predict 3-Year Outcomes in Operatively Treated Patients with Adult Spinal Deformity.(World neurosurgery, 2017-06) Jain, Amit; Kebaish, Khaled M; Sciubba, Daniel M; Hassanzadeh, Hamid; Scheer, Justin K; Neuman, Brian J; Lafage, Virginie; Bess, Shay; Protopsaltis, Themistocles S; Burton, Douglas C; Smith, Justin S; Shaffrey, Christopher I; Hostin, Richard A; Ames, Christopher P; International Spine Study GroupBackground
For patients with adult spinal deformity (ASD), surgical treatment may improve their health-related quality of life. This study investigates when the greatest improvement in outcomes occurs and whether incremental improvements in patient-reported outcomes during the first postoperative year predict outcomes at 3 years.Methods
Using a multicenter registry, we identified 84 adults with ASD treated surgically from 2008 to 2012 with complete 3-year follow-up. Pairwise t tests and multivariate regression were used for analysis. Significance was set at P < 0.01.Results
Mean Oswestry Disability Index (ODI) and Scoliosis Research Society-22r total (SRS-22r) scores improved by 13 and 0.8 points, respectively, from preoperatively to 3 years (both P < 0.001). From preoperatively to 6 weeks postoperatively, ODI scores worsened by 5 points (P = 0.049) and SRS-22r scores improved by 0.3 points (P < 0.001). Between 6 weeks and 1 year, ODI and SRS-22r scores improved by 19 and 0.5 points, respectively (both P < 0.001). Incremental improvements during the first postoperative year predicted 3-year outcomes in ODI and SRS-22r scores (adjusted R2 = 0.52 and 0.42, respectively). There were no significant differences in the measured or predicted 3-year ODI (P = 0.991) or SRS-22r scores (P = 0.986).Conclusions
In surgically treated patients with ASD, the greatest improvements in outcomes occurred between 6 weeks and 1 year postoperatively. A model with incremental improvements from baseline to 6 weeks and from 6 weeks to 1 year can be used to predict ODI and SRS-22r scores at 3 years.Item Open Access Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure.(Hypertension, 2010-06) Smith, Patrick J; Blumenthal, James A; Babyak, Michael A; Craighead, Linda; Welsh-Bohmer, Kathleen A; Browndyke, Jeffrey N; Strauman, Timothy A; Sherwood, AndrewHigh blood pressure increases the risks of stroke, dementia, and neurocognitive dysfunction. Although aerobic exercise and dietary modifications have been shown to reduce blood pressure, no randomized trials have examined the effects of aerobic exercise combined with dietary modification on neurocognitive functioning in individuals with high blood pressure (ie, prehypertension and stage 1 hypertension). As part of a larger investigation, 124 participants with elevated blood pressure (systolic blood pressure 130 to 159 mm Hg or diastolic blood pressure 85 to 99 mm Hg) who were sedentary and overweight or obese (body mass index: 25 to 40 kg/m(2)) were randomized to the Dietary Approaches to Stop Hypertension (DASH) diet alone, DASH combined with a behavioral weight management program including exercise and caloric restriction, or a usual diet control group. Participants completed a battery of neurocognitive tests of executive function-memory-learning and psychomotor speed at baseline and again after the 4-month intervention. Participants on the DASH diet combined with a behavioral weight management program exhibited greater improvements in executive function-memory-learning (Cohen's D=0.562; P=0.008) and psychomotor speed (Cohen's D=0.480; P=0.023), and DASH diet alone participants exhibited better psychomotor speed (Cohen's D=0.440; P=0.036) compared with the usual diet control. Neurocognitive improvements appeared to be mediated by increased aerobic fitness and weight loss. Also, participants with greater intima-medial thickness and higher systolic blood pressure showed greater improvements in executive function-memory-learning in the group on the DASH diet combined with a behavioral weight management program. In conclusion, combining aerobic exercise with the DASH diet and caloric restriction improves neurocognitive function among sedentary and overweight/obese individuals with prehypertension and hypertension.Item Open Access Efficient coding of spatial information in the primate retina.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012-11) Doi, Eizaburo; Gauthier, Jeffrey L; Field, Greg D; Shlens, Jonathon; Sher, Alexander; Greschner, Martin; Machado, Timothy A; Jepson, Lauren H; Mathieson, Keith; Gunning, Deborah E; Litke, Alan M; Paninski, Liam; Chichilnisky, EJ; Simoncelli, Eero PSensory neurons have been hypothesized to efficiently encode signals from the natural environment subject to resource constraints. The predictions of this efficient coding hypothesis regarding the spatial filtering properties of the visual system have been found consistent with human perception, but they have not been compared directly with neural responses. Here, we analyze the information that retinal ganglion cells transmit to the brain about the spatial information in natural images subject to three resource constraints: the number of retinal ganglion cells, their total response variances, and their total synaptic strengths. We derive a model that optimizes the transmitted information and compare it directly with measurements of complete functional connectivity between cone photoreceptors and the four major types of ganglion cells in the primate retina, obtained at single-cell resolution. We find that the ganglion cell population exhibited 80% efficiency in transmitting spatial information relative to the model. Both the retina and the model exhibited high redundancy (~30%) among ganglion cells of the same cell type. A novel and unique prediction of efficient coding, the relationships between projection patterns of individual cones to all ganglion cells, was consistent with the observed projection patterns in the retina. These results indicate a high level of efficiency with near-optimal redundancy in visual signaling by the retina.Item Open Access Energy recovery in individuals with knee osteoarthritis.(Osteoarthritis Cartilage, 2014-06) Sparling, TL; Schmitt, D; Miller, CE; Guilak, F; Somers, TJ; Keefe, FJ; Queen, RMOBJECTIVE: Pathological gaits have been shown to limit transfer between potential (PE) and kinetic (KE) energy during walking, which can increase locomotor costs. The purpose of this study was to examine whether energy exchange would be limited in people with knee osteoarthritis (OA). METHODS: Ground reaction forces during walking were collected from 93 subjects with symptomatic knee OA (self-selected and fast speeds) and 13 healthy controls (self-selected speed) and used to calculate their center of mass (COM) movements, PE and KE relationships, and energy recovery during a stride. Correlations and linear regressions examined the impact of energy fluctuation phase and amplitude, walking velocity, body mass, self-reported pain, and radiographic severity on recovery. Paired t-tests were run to compare energy recovery between cohorts. RESULTS: Symptomatic knee OA subjects displayed lower energetic recovery during self-selected walking speeds than healthy controls (P = 0.0018). PE and KE phase relationships explained the majority (66%) of variance in recovery. Recovery had a complex relationship with velocity and its change across speeds was significantly influenced by the self-selected walking speed of each subject. Neither radiographic OA scores nor subject self-reported measures demonstrated any relationship with energy recovery. CONCLUSIONS: Knee OA reduces effective exchange of PE and KE, potentially increasing the muscular work required to control movements of the COM. Gait retraining may return subjects to more normal patterns of energy exchange and allow them to reduce fatigue.Item Open Access Evaluation of integrated respiratory gating systems on a Novalis Tx system.(Journal of applied clinical medical physics, 2011-04-04) Chang, Zheng; Liu, Tonghai; Cai, Jing; Chen, Qing; Wang, Zhiheng; Yin, Fang-FangThe purpose of this study was to investigate the accuracy of motion tracking and radiation delivery control of integrated gating systems on a Novalis Tx system. The study was performed on a Novalis Tx system, which is equipped with Varian Real-time Position Management (RPM) system, and BrainLAB ExacTrac gating systems. In this study, the two systems were assessed on accuracy of both motion tracking and radiation delivery control. To evaluate motion tracking, two artificial motion profiles and five patients' respiratory profiles were used. The motion trajectories acquired by the two gating systems were compared against the references. To assess radiation delivery control, time delays were measured using a single-exposure method. More specifically, radiation is delivered with a 4 mm diameter cone within the phase range of 10%-45% for the BrainLAB ExacTrac system, and within the phase range of 0%-25% for the Varian RPM system during expiration, each for three times. Radiochromic films were used to record the radiation exposures and to calculate the time delays. In the work, the discrepancies were quantified using the parameters of mean and standard deviation (SD). Pearson's product-moment correlational analysis was used to test correlation of the data, which is quantified using a parameter of r. The trajectory profiles acquired by the gating systems show good agreement with those reference profiles. A quantitative analysis shows that the average mean discrepancies between BrainLAB ExacTrac system and known references are 1.5 mm and 1.9 mm for artificial and patient profiles, with the maximum motion amplitude of 28.0 mm. As for the Varian RPM system, the corresponding average mean discrepancies are 1.1 mm and 1.7 mm for artificial and patient profiles. With the proposed single-exposure method, the time delays are found to be 0.20 ± 0.03 seconds and 0.09 ± 0.01 seconds for BrainLAB ExacTrac and Varian RPM systems, respectively. The results indicate the systems can track motion and control radiation delivery with reasonable accuracy. The proposed single-exposure method has been demonstrated to be feasible in measuring time delay efficiently.Item Open Access Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.(Age (Dordr), 2013-04) Soerensen, Mette; Dato, Serena; Tan, Qihua; Thinggaard, Mikael; Kleindorp, Rabea; Beekman, Marian; Suchiman, H Eka D; Jacobsen, Rune; McGue, Matt; Stevnsner, Tinna; Bohr, Vilhelm A; de Craen, Anton JM; Westendorp, Rudi GJ; Schreiber, Stefan; Slagboom, P Eline; Nebel, Almut; Vaupel, James W; Christensen, Kaare; Christiansen, LeneIn this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.Item Open Access From spiking neuron models to linear-nonlinear models.(PLoS Comput Biol, 2011-01-20) Ostojic, Srdjan; Brunel, NicolasNeurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.
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