scholarly journals Reproducible abnormalities of functional gradient reliably predict clinical and cognitive symptoms in schizophrenia

2020 ◽  
Author(s):  
Meng Wang ◽  
Ang Li ◽  
Yong Liu ◽  
Hao Yan ◽  
Yuqing Sun ◽  
...  

AbstractBackgroundSchizophrenia (SZ) typically manifests heterogeneous phenotypes involving positive, negative and cognitive symptoms. However, the underlying neural mechanisms of these symptoms keep unclear. Functional gradient is a fascinating measure to characterize continuous, hierarchical organization of brain.MethodsWe aimed to investigate whether reproducible disruptions of functional gradient existed in SZ compared to normal controls (NC), and these abnormalities were associated with severity of clinical and cognitive symptoms in SZ. All analyses were implemented in two independent large-sample multi-site datasets (discovery dataset, 400 SZ and 336 NC; replication dataset, 279 SZ and 262 NC). First, functional gradient across cerebral cortex was calculated in each subject. Second, vertex-wise comparisons of cortical gradient between SZ and NC groups were performed to identify abnormalities in SZ. Meanwhile, reproducible and robustness analyses were implemented to validate these abnormalities. Finally, regression analyses were performed using generalized additive models to link these abnormalities to severity of clinical and cognitive symptoms in SZ.ResultsWe found an abnormal gradient map in SZ in the discovery dataset, which was reproducible in the replication dataset. The abnormal gradient pattern was also robust when performing methodological alternatives and control analyses. Further, these reproducible abnormalities can reliably predict symptoms of clinical and cognitive domains across the two independent datasets.ConclusionThese findings demonstrated that alterations in functional gradient can provide a reliable signature of SZ, characterizing the heterogenous symptoms of clinical or cognitive domains, and may be further investigated to understand the neurobiological mechanisms of these symptoms.Impact StatementIn our study, using functional gradient measure and statistical learning technology and two independent multi-site case-control resting-state fMRI datasets (discovery dataset: 736 subjects; replication dataset: 541 subjects), we comprehensively investigated functional hierarchical organization in the cerebral cortex of SZ and its association with interindividual severity of symptoms. We found reproducible and robust abnormalities of functional gradient existed in SZ, which provided a reliable signature to characterize negative and general psychopathology symptoms, as well as cognitive deficits. Our findings can provide new insights to understand the neurobiological mechanisms of clinical and cognitive symptoms in SZ.

Author(s):  
François Freddy Ateba ◽  
Manuel Febrero-Bande ◽  
Issaka Sagara ◽  
Nafomon Sogoba ◽  
Mahamoudou Touré ◽  
...  

Mali aims to reach the pre-elimination stage of malaria by the next decade. This study used functional regression models to predict the incidence of malaria as a function of past meteorological patterns to better prevent and to act proactively against impending malaria outbreaks. All data were collected over a five-year period (2012–2017) from 1400 persons who sought treatment at Dangassa’s community health center. Rainfall, temperature, humidity, and wind speed variables were collected. Functional Generalized Spectral Additive Model (FGSAM), Functional Generalized Linear Model (FGLM), and Functional Generalized Kernel Additive Model (FGKAM) were used to predict malaria incidence as a function of the pattern of meteorological indicators over a continuum of the 18 weeks preceding the week of interest. Their respective outcomes were compared in terms of predictive abilities. The results showed that (1) the highest malaria incidence rate occurred in the village 10 to 12 weeks after we observed a pattern of air humidity levels >65%, combined with two or more consecutive rain episodes and a mean wind speed <1.8 m/s; (2) among the three models, the FGLM obtained the best results in terms of prediction; and (3) FGSAM was shown to be a good compromise between FGLM and FGKAM in terms of flexibility and simplicity. The models showed that some meteorological conditions may provide a basis for detection of future outbreaks of malaria. The models developed in this paper are useful for implementing preventive strategies using past meteorological and past malaria incidence.


Author(s):  
Mark David Walker ◽  
Mihály Sulyok

Abstract Background Restrictions on social interaction and movement were implemented by the German government in March 2020 to reduce the transmission of coronavirus disease 2019 (COVID-19). Apple's “Mobility Trends” (AMT) data details levels of community mobility; it is a novel resource of potential use to epidemiologists. Objective The aim of the study is to use AMT data to examine the relationship between mobility and COVID-19 case occurrence for Germany. Is a change in mobility apparent following COVID-19 and the implementation of social restrictions? Is there a relationship between mobility and COVID-19 occurrence in Germany? Methods AMT data illustrates mobility levels throughout the epidemic, allowing the relationship between mobility and disease to be examined. Generalized additive models (GAMs) were established for Germany, with mobility categories, and date, as explanatory variables, and case numbers as response. Results Clear reductions in mobility occurred following the implementation of movement restrictions. There was a negative correlation between mobility and confirmed case numbers. GAM using all three categories of mobility data accounted for case occurrence as well and was favorable (AIC or Akaike Information Criterion: 2504) to models using categories separately (AIC with “driving,” 2511. “transit,” 2513. “walking,” 2508). Conclusion These results suggest an association between mobility and case occurrence. Further examination of the relationship between movement restrictions and COVID-19 transmission may be pertinent. The study shows how new sources of online data can be used to investigate problems in epidemiology.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Narayan Sharma ◽  
René Schwendimann ◽  
Olga Endrich ◽  
Dietmar Ausserhofer ◽  
Michael Simon

Abstract Background Understanding how comorbidity measures contribute to patient mortality is essential both to describe patient health status and to adjust for risks and potential confounding. The Charlson and Elixhauser comorbidity indices are well-established for risk adjustment and mortality prediction. Still, a different set of comorbidity weights might improve the prediction of in-hospital mortality. The present study, therefore, aimed to derive a set of new Swiss Elixhauser comorbidity weightings, to validate and compare them against those of the Charlson and Elixhauser-based van Walraven weights in an adult in-patient population-based cohort of general hospitals. Methods Retrospective analysis was conducted with routine data of 102 Swiss general hospitals (2012–2017) for 6.09 million inpatient cases. To derive the Swiss weightings for the Elixhauser comorbidity index, we randomly halved the inpatient data and validated the results of part 1 alongside the established weighting systems in part 2, to predict in-hospital mortality. Charlson and van Walraven weights were applied to Charlson and Elixhauser comorbidity indices. Derivation and validation of weightings were conducted with generalized additive models adjusted for age, gender and hospital types. Results Overall, the Elixhauser indices, c-statistic with Swiss weights (0.867, 95% CI, 0.865–0.868) and van Walraven’s weights (0.863, 95% CI, 0.862–0.864) had substantial advantage over Charlson’s weights (0.850, 95% CI, 0.849–0.851) and in the derivation and validation groups. The net reclassification improvement of new Swiss weights improved the predictive performance by 1.6% on the Elixhauser-van Walraven and 4.9% on the Charlson weights. Conclusions All weightings confirmed previous results with the national dataset. The new Swiss weightings model improved slightly the prediction of in-hospital mortality in Swiss hospitals. The newly derive weights support patient population-based analysis of in-hospital mortality and seek country or specific cohort-based weightings.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1252.2-1253
Author(s):  
R. Garofoli ◽  
M. Resche-Rigon ◽  
M. Dougados ◽  
D. Van der Heijde ◽  
C. Roux ◽  
...  

Background:Axial spondyloarthritis (axSpA) is a chronic rheumatic disease that encompasses various clinical presentations: inflammatory chronic back pain, peripheral manifestations and extra-articular manifestations. The current nomenclature divides axSpA in radiographic (in the presence of radiographic sacroiliitis) and non-radiographic (in the absence of radiographic sacroiliitis, with or without MRI sacroiliitis. Given that the functional burden of the disease appears to be greater in patients with radiographic forms, it seems crucial to be able to predict which patients will be more likely to develop structural damage over time. Predictive factors for radiographic progression in axSpA have been identified through use of traditional statistical models like logistic regression. However, these models present some limitations. In order to overcome these limitations and to improve the predictive performance, machine learning (ML) methods have been developed.Objectives:To compare ML models to traditional models to predict radiographic progression in patients with early axSpA.Methods:Study design: prospective French multicentric cohort study (DESIR cohort) with 5years of follow-up. Patients: all patients included in the cohort, i.e. 708 patients with inflammatory back pain for >3 months but <3 years, highly suggestive of axSpA. Data on the first 5 years of follow-up was used. Statistical analyses: radiographic progression was defined as progression either at the spine (increase of at least 1 point per 2 years of mSASSS scores) or at the sacroiliac joint (worsening of at least one grade of the mNY score between 2 visits). Traditional modelling: we first performed a bivariate analysis between our outcome (radiographic progression) and explanatory variables at baseline to select the variables to be included in our models and then built a logistic regression model (M1). Variable selection for traditional models was performed with 2 different methods: stepwise selection based on Akaike Information Criterion (stepAIC) method (M2), and the Least Absolute Shrinkage and Selection Operator (LASSO) method (M3). We also performed sensitivity analysis on all patients with manual backward method (M4) after multiple imputation of missing data. Machine learning modelling: using the “SuperLearner” package on R, we modelled radiographic progression with stepAIC, LASSO, random forest, Discrete Bayesian Additive Regression Trees Samplers (DBARTS), Generalized Additive Models (GAM), multivariate adaptive polynomial spline regression (polymars), Recursive Partitioning And Regression Trees (RPART) and Super Learner. Finally, the accuracy of traditional and ML models was compared based on their 10-foldcross-validated AUC (cv-AUC).Results:10-fold cv-AUC for traditional models were 0.79 and 0.78 for M2 and M3, respectively. The 3 best models in the ML algorithm were the GAM, the DBARTS and the Super Learner models, with 10-fold cv-AUC of: 0.77, 0.76 and 0.74, respectively (Table 1).Table 1.Comparison of 10-fold cross-validated AUC between best traditional and machine learning models.Best modelsCross-validated AUCTraditional models M2 (step AIC method)0.79 M3 (LASSO method)0.78Machine learning approach SL Discrete Bayesian Additive Regression Trees Samplers (DBARTS)0.76 SL Generalized Additive Models (GAM)0.77 Super Learner0.74AUC: Area Under the Curve; AIC: Akaike Information Criterion; LASSO: Least Absolute Shrinkage and Selection Operator; SL: SuperLearner. N = 295.Conclusion:Traditional models predicted better radiographic progression than ML models in this early axSpA population. Further ML algorithms image-based or with other artificial intelligence methods (e.g. deep learning) might perform better than traditional models in this setting.Acknowledgments:Thanks to the French National Society of Rheumatology and the DESIR cohort.Disclosure of Interests:Romain Garofoli: None declared, Matthieu resche-rigon: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Christian Roux: None declared, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fahimeh Ramezani Tehrani ◽  
Maryam Rahmati ◽  
Fatemeh Mahboobifard ◽  
Faezeh Firouzi ◽  
Nazanin Hashemi ◽  
...  

Abstract Background The majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH. Methods A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method. Main results and the role of chance Two optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years. Conclusions Application of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.


Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 168
Author(s):  
Xueqin Liu ◽  
Hui Wang ◽  
Dahan He ◽  
Xinpu Wang ◽  
Ming Bai

Beetles are key insect species in global biodiversity and play a significant role in steppe ecosystems. In the temperate steppe of China, the increasing degeneration of the grasslands threatens beetle species and their habitat. Using Generalized Additive Models (GAMs), we aimed to predict and map beetle richness patterns within the temperate steppe of Ningxia (China). We tested 19 environmental predictors including climate, topography, soil moisture and space as well as vegetation. Climatic variables (temperature, precipitation, soil temperature) consistently appeared among the most important predictors for beetle groups modeled. GAM generated predictive cartography for the study area. Our models explained a significant percentage of the variation in carabid beetle richness (79.8%), carabid beetle richness distribution seems to be mainly influenced by temperature and precipitation. The results have important implications for management and conservation strategies and also provides evidence for assessing and making predictions of beetle diversity across the steppe.


Mathematics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 299
Author(s):  
Jaime Pinilla ◽  
Miguel Negrín

The interrupted time series analysis is a quasi-experimental design used to evaluate the effectiveness of an intervention. Segmented linear regression models have been the most used models to carry out this analysis. However, they assume a linear trend that may not be appropriate in many situations. In this paper, we show how generalized additive models (GAMs), a non-parametric regression-based method, can be useful to accommodate nonlinear trends. An analysis with simulated data is carried out to assess the performance of both models. Data were simulated from linear and non-linear (quadratic and cubic) functions. The results of this analysis show how GAMs improve on segmented linear regression models when the trend is non-linear, but they also show a good performance when the trend is linear. A real-life application where the impact of the 2012 Spanish cost-sharing reforms on pharmaceutical prescription is also analyzed. Seasonality and an indicator variable for the stockpiling effect are included as explanatory variables. The segmented linear regression model shows good fit of the data. However, the GAM concludes that the hypothesis of linear trend is rejected. The estimated level shift is similar for both models but the cumulative absolute effect on the number of prescriptions is lower in GAM.


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