Individual Deviations Research Articles

Investigation of intermolecular interactions in binary mixtures of N,N-dimethyl benzyl amine with higher alkanols (N,N-dimethyl benzyl amine with 1-octanol, 1-nonanol, 1-decanol)

ABSTRACT Measurements of densities (ρ), speeds of sound (u), and viscosities (η) for binary mixtures of N,N-dimethyl benzyl amine (DMBA) with 1-octanol (D1), 1-nonanol (D2), and 1-decanol (D3) were performed across temperatures from 303.15 K to 313.15 K under atmospheric pressure, covering all composition ranges. These experimental results were utilised to calculate the excess molar volume, excess isentropic compressibility, viscosity deviation, and the excess Gibbs free energy of activation for viscous flow. Calculations for partial molar properties and infinite dilution partial molar properties were also carried out for each binary mixture. The dominant intermolecular interactions within these mixtures were analysed using the PFP theory. Additionally, the Jouyban−Acree model was applied to predict the thermo physical properties such as density, speed of sound, and viscosity. The model’s accuracy was evaluated by comparing predicted values with experimental data through mean relative deviations (MRDs) and individual relative deviations (IRDs).

B-258 Rapid clozapine blood levels on the Beckman Coulter DxC 500 AU

Abstract Background Clozapine is the most effective drug for treatment-resistant schizophrenia. Multiple guidelines strongly recommend clozapine therapeutic drug monitoring (TDM). Measuring clozapine blood levels provides essential information when there are questions of medication adherence, efficacy, toxicity, medication interactions, or concern over other factors that may influence clozapine levels. Turnaround time is essential for effective clinical decisions. However, with liquid-chromatography/mass spectrometry, clozapine levels can take days to report results. To address the medical need for a faster turnaround time, a rapid clozapine immunoassay was developed for automated clinical chemistry analyzers. The immunoassay measuring range is based on established APA Practice Guidelines and ASCP/AGNP Consensus Statement. We developed an analyzer application for the DxC 500 AU (time to first result < 9 minutes) to expand the availability of rapid clozapine blood level testing. Methods The performance of the FDA-cleared clozapine assay was evaluated on the DxC 500 AU according to CLSI guidelines. Precision testing was performed with three clozapine spiked pools over five days with five replicates per sample. Precision sample recovery was assessed to their theoretical spike concentration. Linearity was verified with five spiked serum samples covering the measuring range. Method comparison was performed with 40 remnant patient samples vs. the Beckman Coulter AU480. Results Repeatability CV was ≤5.5% and within-laboratory precision CV was ≤6.1%. Individual deviation was ±20% and mean deviation was ±2% for all samples. Deviation from linearity was <3%. Deming regression statistics for the method comparison were a slope of 0.987, an intercept of 5.7, and an R of 0.9948. The methods are statistically equivalent: the 99% confidence limits contained 1 and 0 for the slope and intercept respectively. Conclusions The precision, recovery, linearity, and method comparison results for clozapine on the DxC 500 AU demonstrate that the analyzer can be used to generate robust results for clozapine.

A-038 Interlaboratory Comparison of Parathyroid Hormone Analytical Results Across Clinical Assays from 8 Manufacturers - Steps Towards Standardization

Abstract Background Parathyroid hormone (PTH) is an 84 amino acid peptide produced by the parathyroid gland and is a key biomarker used for the diagnosis and treatment of Chronic Kidney Disease-Mineral and Bone Disorder, as well as hypo- and hyperparathyroidism. PTH clinical assays were previously reported to exhibit significant inter-assay measurement variability, which limits the utility of PTH as a diagnostic biomarker and can result in the misclassification of patients. Thus, there is a need for PTH clinical assay standardization to improve clinical assay measurement agreement. The Centers for Disease Control and Prevention’s Clinical Standardization Program (CDC-CSP) will launch a PTH standardization program, which is in support of and coordinated with the IFCC Committee on Bone Metabolism. In preparation, the CDC-CSP conducted an Inter-Laboratory Comparison Study to evaluate the current status of PTH inter-assay variability and to investigate potential sources of variability. Methods Eight PTH assay manufacturer’s laboratories measured PTH in 42 deidentified, fresh-frozen single donor serum samples in duplicate over 2 independent runs. Sample PTH concentrations ranged from 1.3 - 324 pg/mL, based on initial screening values. Five manufacturers submitted data for 2 different assays, resulting in PTH measurements from 13 assays total. Data were submitted to the CDC CSP for analysis. Results Assay precision was <5% for 10/13 measurement procedures (MP) assessed and 3 MPs exhibited precisions between 5 - 18%. Assay-specific PTH measurements demonstrated good linear correlation compared to the all-assay mean concentration. Interestingly, inter-assay variability increased with increasing PTH concentrations, with individual sample standard deviations increasing from 2.9 - 123, with a mean SD of 24.1 and individual sample CVs increasing from 18.9 - 44.5%, with a mean CV of 24.2%. Conclusions This study provides new insights into PTH inter-assay variability and assay performance for assays commonly used in the clinical setting. The findings of this PTH Interlaboratory Comparison Study establish a baseline for PTH inter-assay variability and will guide future PTH standardization efforts.

Proactive conformance checking: An approach for predicting deviations in business processes

Modern business processes are subject to an increasing number of external and internal regulations. Compliance with these regulations is crucial for the success of organizations. To ensure this compliance, process managers can identify and mitigate deviations between the predefined process behavior and the executed process instances by means of conformance checking techniques. However, these techniques are inherently reactive, meaning that they can only detect deviations after they have occurred. It would be desirable to detect and mitigate deviations before they occur, enabling managers to proactively ensure compliance of running process instances. In this paper, we propose Business Process Deviation Prediction (BPDP), a novel predictive approach that relies on a supervised machine learning model to predict which deviations can be expected in the future of running process instances. BPDP is able to predict individual deviations as well as deviation patterns. Further, it provides the user with a list of potential reasons for predicted deviations. Our evaluation shows that BPDP outperforms existing methods for deviation prediction. Following the idea of action-oriented process mining, BPDP thus enables process managers to prevent deviations in early stages of running process instances.

Comparison of joint kinematics from optical marker-based and inertial sensor-based motion capture during change-of-direction movements

The development of inertial measurement units (IMUs) has opened up possibilities to test kinematics of sports movements in natural environments (Di Paolo et al., 2023). This advantage over lab-based optical motion capture (OMC) comes at the cost of inherent inaccuracies. Especially, fast multidirectional movements including de- and accelerations pose a challenge for inertial-based movement reconstruction with limited task-specific validation research available (Heuvelmans et al., 2022). Therefore, we aimed to test the validity of IMU-based kinematics in a 180° change of direction (COD) task to provide insight into the applicability for future on-field ACL injury risk research. Twenty-six sports science students were equipped with eight IMU sensors of the Noraxon Ultium Motion System and an adaption of the Plug-in-Gait markerset (53 markers) recorded by a VICON OMC system. They performed five 180° anti-clockwise CODs at their maximum speed. As an example for sagittal and frontal plane angles relevant for ACL injury risk, the knee flexion and abduction angle at the initial contact of the cutting step (right leg) were calculated using the Noraxon MyoMotion software for IMU-recorded data and OpenSim for marker-based OMC data. At the time of abstract submission, the data of five (randomly chosen) participants had been analysed. More participants and more joint angle outcomes will be included in follow-up analyses. Deviations between IMU-generated and OMC-generated joint angles are depicted in Figure 1. Within subjects, deviations below 1.5 standard deviations were observed. Between subjects, deviations ranged from 0° and 22° in knee flexion angles and 0° and 11° in knee abduction angles. A general trend towards higher joint angles measured by the IMU system is noticeable, suggesting a possible off-set error. For four out of five participants, the knee flexion deviation was below 10°, which can be considered an accuracy which is tolerable but requires consideration in the interpretation (< 2°: good accuracy, 2-5°: acceptable accuracy, 5-10°: tolerable accuracy, > 10° unbearable accuracy; Bessone et al., 2022). Deviations in knee abduction angles appear too large given the small physiological joint range and motion in this plane. This preliminary analysis of individual deviations suggests acceptable deviations between IMU and OMC measurements regarding knee flexion but problematic deviations for knee abduction. Prospectively, we aim to investigate possible off-set corrections, e.g. through a better alignment of the underlying biomechanical models, and alternative approaches for IMU-based movement reconstruction, e.g. through optimal control simulations (Nitschke et al., 2024).

217 Effect of within-litter competition on lamb survivability

Abstract The objective of this study was to evaluate the influence of lamb and littermate competition on lamb survivability to weaning. Litter sex composition and litter birth weight variation were the primary considerations for influencing competition. Records from maternal dual-purpose (Polypay, Rambouillet, and Targhee) and terminal breeds [Suffolk and Paternal Composite (PC; 3/8 Columbia, 3/8 Suffolk, 1/4 Texel)] were used, with 18,654 single and 56,324 twin records from all breeds and 11,082 triplet records from the 3 maternal breeds. Records were reported from 1980 to 2023, except for the PC, which began inter se mating in 2009. Lamb survivability to 90 d was analyzed using a Bayesian logistic regression model with the logit link function. Lamb survivability was assumed binomially distributed and influenced by age of dam, birth year, lamb sex, and sex of littermates as fixed effects. The relationship among littermates was also accounted for. Least squares means were transformed from the log odds scale to the probability scale. Birth weight was assumed normally distributed and influenced by the same fixed effects as lamb survival and was analyzed using a linear mixed model. Lamb survivability was also analyzed using the same model described above but including mean litter weight and individual birth weight deviation as linear covariates. Accounting for mean litter birth weight and individual birth weight deviation removed the birth weight differences between the sexes, leaving only true sex differences between lambs for survivability. For single births, females tended to have greater survivability than males when adjusted for birth weight for all breeds but was only significant (P < 0.05) for Rambouillet and Targhee. For maternal breeds, females in twin litters had significantly greater survivability (P < 0.05) than their male counterparts when adjusted for birth weight; differences in terminal breeds were not significant (Table 1). Males in twin litters had heavier birth weights than females (P < 0.05) for all breeds. Triplet born females for all litter-sex combinations had significantly higher survival than males (P < 0.05) for Polypay when adjusted for birth weight. Females in female-female-male (FFM) litters had 76.4% survival versus 58.9% for males while females in female-male-male (FMM) litters had 75.9% versus 66.7% for males. When lamb survivability was adjusted for birth weight, Rambouillet females in FFM litters had 72.2% survival compared with 59.9% for males (P < 0.05) and females in FMM litters had 73.0% survival compared with 63.8% for males. Similar significant differences were observed for FFM and FMM Targhee litters. This study suggests lamb performance is influenced by its littermate(s). Changes in postnatal management of mixed-sex litters may benefit overall lamb survival. USDA is an equal opportunity provider and employer.

The Association of Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease with Cognitive Intra-Individual Variability

Abstract Objective Cognitive intra-individual variability (IIV) is a sensitive predictor of cognitive decline and disease severity in Alzheimer’s disease (AD). Despite its sensitivity, whether IIV is merely a psychometric artifact or disease pathology biomarker remains unknown. The present study evaluated the association between IIV and cerebrospinal fluid (CSF) biomarkers of AD. Method Participants included 422 individuals from the National Alzheimer’s Coordinating Center Unified Dataset 3.0 who completed baseline neuropsychological assessment and had CSF data. All participants were adult monolingual English speakers. Participants with vision or hearing impairments were excluded. Cases were stratified into cognitively normal (n = 267) and AD groups (n = 155; mild cognitive impairment = 50, dementia = 105). Cross-sectional IIV was calculated by obtaining the individual standard deviation (iSD) of ten cognitive tests. Finally, the coefficient of variation (CoV) was computed by dividing iSD by the participant’s overall test battery mean. Non-parametric Spearman-rank correlations were used to assess the relation between CoV and CSF biomarkers, including beta-amyloid 1–42, total tau (t-tau), and phosphorylated tau (p-tau181). Results In the AD group, CoV was positively correlated with p-tau181 (r = 0.285, p = 0.003) and t-tau (r = 0.241, p = 0.009), and negatively correlated with beta-amyloid 1–42 (r = −0.314, p < 0.001). Correlations between CoV and CSF biomarkers were not significant in the cognitively normal group for beta-amyloid 1–42 (r = 0.076, p = 0.215), p-tau181 (r = −0.014, p = 0.840), and t-tau (r = −0.046, p = 0.485). Conclusions In people with mild cognitive impairment and dementia of presumed AD etiology, cognitive IIV is associated with CSF biomarkers. These findings provide preliminary evidence that IIV is not merely a statistical artifact, but is associated with AD neuropathology.

Evaluation of the presence of nasal septum deviations in individuals with different skeletal malocclusions

OBJECTIVE: The aim of this study was to evaluate the presence of deviated septum in individuals with different skeletal malocclusions. MATERIALS AND METHOD: The study was performed on cone beam computed tomography images of a total of 159 individuals, 53 in each Class I, Class II, and Class III skeletal malocclusion. Nasal septum deviation was analysed in three groups as mild (type 1; <9°), moderate (type 2; 9-15°), and severe (type3; >15°). In addition, the presence of concha bullosa in different skeletal malocclusions was evaluated. The data were analyzed statistically using the Chi-square test and One-way Analysis of Variance (ANOVA). The relationship betweenskeletal malocclusions and types of deviation was determined using Cramèr’s V analysis. RESULTS: There are statistically significant differences between type 2 and type 3 in individuals with Class I skeletal malocclusion and between type 1 and type 3 in individuals with Class II skeletal malocclusion (p=0.046; p<0.01 respectively). In individuals with Class III skeletal malocclusion, no difference was observed between deviation types. In addition, a weak correlation was found between skeletal malocclusion and deviation types (Cramèr’s V = 0.213). No significant difference was observed between the groups in terms of concha bullosa and deviation side (p=0.215). CONCLUSION: Although a significant difference was observed in terms of deviation type in individuals with Class I and II skeletal malocclusion, a weak correlation was observed between the increase in deviation severity and skeletal malocclusions.

A new diagnostic for the null test of dynamical dark energy in light of DESI 2024 and other BAO data

We introduce a new diagnostic for the null tests of dynamical dark energy alongside two other combined equivalent diagnostics. These diagnostics are useful, especially when we include anisotropic baryon acoustic oscillation (BAO) data in an analysis, to quantify the deviations from the standard ΛCDM model. We also consider another diagnostic for isotropic BAO observations. These null tests are independent of any late-time dark energy model or parametrization. With these diagnostics, we study the evidence for dynamical dark energy in light of Dark Energy Spectroscopic Instrument (DESI) 2024 data combined with cosmic microwave background (CMB) observations of the Planck 2018 mission and local H 0 measurements. We find no strong evidence for dynamical dark energy. The exclusion of the individual deviations at the effective redshift 0.51 of the DESI 2024 data makes the evidence even weaker. We get nearly similar results for other non-DESI BAO data. Both for DESI 2024 and other non-DESI BAO data, the evidence is almost independent of early-time physics. The evidence corresponding to the SHOES value of H 0 is higher than the corresponding tRGB value of H 0 for all combinations of data, but still not strong enough to reject the flat ΛCDM model.

Application effectiveness of "Youxin-1" in genetic diversity and structure analysis of local chickens.

China's local chicken breeds are rich in resources, and have formed different germplasm characteristics in the process of long-term selection and evolution. Scientific assessment of population genetic diversity and identification of inter-breed genetic structure are of great value to the protection and innovative utilization of local chicken breed resource. In order to evaluate the application effectiveness of 23K SNP chip "Youxin-1" in the analysis of genetic diversity and genetic structure of local chickens, we used RADseq to identify genomic genetic variation of 21 local chicken breeds and developed 23K chip "Youxin-1". The genetic statistics of each variety were calculated based on two sets of SNP data, and correlation, fitting and phylogenetic analysis were carried out to evaluate the application effectiveness of the chip. The results showed that the observed heterozygosity (Ho), polymorphism information content (PIC), inbred coefficient (FROH) and genetic differentiation coefficient (Fst) calculated based on the two SNP data sets were basically consistent in the 21 local chicken breeds. The genetic diversity of Langya chicken (LA), Piao chicken (PJ) and Wenchang chicken (WC) was relatively rich. The genetic diversity of Bian chickens (BJ), Langshan chickens (LS), Gushi chickens (GS), Dongxiang blue-eggshell chickens (DX) and Beijing fatty chickens (BY) was relatively poor, and the correlation coefficients of Ho, PIC, FROH and average Fst in the two groups were 0.794, 0.901, 0.926 and 0.984, respectively, all reaching extremely significant levels (P<0.01) with a high degree of fit (P<0.001) and R2 were 0.644, 0.827, 0.916 and 0.927. For the two sets of SNP data, the evolutionary tree constructed by neighbor-joining (NJ) method and maximum likelihood (ML) method was reasonable, and the 21 local chicken breeds were generally divided into six categories, which was consistent with the formation history and geographical distribution of the varieties. The 23K chip also realized reasonable clustering of the five new varieties without individual deviation. There are some differences in the estimation of genetic statistics using SNP with different densities, and data standardization is needed. 23K chip has good efficacy in the analysis of genetic diversity and structure of local chickens.

Physico-chemical studies of non-aqueous binary liquid mixtures of N-methyl aniline with amino alcohols at various temperatures

ABSTRACT Densities (ρ), speeds of sound (u) and viscosities (η) for three binary mixtures of N-methyl aniline with amino alcohols (3-amino-propan-1-ol, 2-amino-2-methyl-propan-1-ol and 1-amino propan-2-ol) were measured at temperatures ranging from 303.15 to 313.15 K and at atmospheric pressure across the entire composition range. Excess molar volume, excess isentropic compressibility, deviation in viscosity, and excess Gibbs free energy of activation of viscous flow were calculated using experimental data. Partial molar properties and infinite dilution molar partial properties were also determined for each binary system. The Prigogine-Flory-Patterson theory is used to identify the most important interaction. The results of the Jouyban-Acree model are discussed in terms of the mean relative deviation and individual relative deviation between the calculated and experimental densities, speed of sound, and viscosities as an accuracy criterion. FTIR studies have also been added to confirm the experimental findings of the investigated mixtures.

Molecular interactions and thermodynamic modelling of N,N-dimethyl benzyl amine-alkoxy ethanol mixtures: an FT-IR spectroscopy and Jouyban–Acree model approach

ABSTRACT This study examines intermolecular interactions in binary mixtures of N,N-dimethyl benzyl amine (DMBA) with short-chain alkoxy ethanols (2-methoxy ethanol (ME), 2-ethoxy ethanol (EE) and 2-butoxy ethanol (BE)). Densities (ρ), speeds of sound (u) and viscosities (η) were measured from 303.15 K to 313.15 K at atmospheric pressure for all compositions. These data were used to determine excess thermodynamic and transport properties: excess molar volume (V E ), excess isentropic compressibility (κs E ), viscosity deviation (Δη) and excess Gibbs free energy of activation (ΔG *E ). Partial and infinite dilution molar partial properties were also calculated. Results focus on complex formation driven by chemical forces. The Jouyban–Acree model predicted these properties, with accuracy assessed using mean relative deviations (MRDs) and individual relative deviations (IRDs). FTIR spectroscopy provided additional insights into intermolecular interactions.

Jouyban–Acree model assessment for physico-chemical properties of N,N-Dimethylbenzylamine with isomeric chlorobenzene systems

ABSTRACT Densities (ρ), speeds of sound (u), and viscosities (η) of binary mixtures of N,N-dimethyl benzyl amine (DMBA) with 1,2-dichlorobenzene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB), and 1,2,4-trichlorobenzene (1,2,4-TCB) were measured at temperatures ranging from 303.15 K to 313.15 K for selected compositions. Excess molar volume (V E ), excess isentropic compressibility (κ s E ), viscosity deviation (Δη), and excess Gibbs free energy for activation of viscous flow (ΔG *E ) were subsequently determined from the experimental data. The obtained results were analysed to elucidate the nature of intermolecular interactions, specifically focusing on attractive forces, steric hindrance or hetero-association within the mixtures. The Prigogine–Flory–Patterson (PFP) theory was employed to identify the dominant type of molecular interaction. The Jouyban–Acree model was applied to calculate densities, speeds of sound, and viscosities. The accuracy of the model was evaluated using mean relative deviations (MRDs) and individual relative deviations (IRDs) between the calculated and experimental values.

Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers.

Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers. We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET. Normative modeling estimated individual-level abnormal deviations in amyloid-positive individuals compared to amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels to assess intra-group heterogeneity. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN. Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression. Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.

Breeding for resilience in finishing pigs can decrease tail biting, lameness and mortality

BackgroundPrevious research showed that deviations in longitudinal data are heritable and can be used as a proxy for pigs’ general resilience. However, only a few studies investigated the relationship between these resilience traits and other traits related to resilience and welfare. Therefore, this study investigated the relationship between resilience traits derived from deviations in longitudinal data and traits related to animal resilience, health and welfare, such as tail and ear biting wounds, lameness and mortality.ResultsIn our experiment, 1919 finishing pigs with known pedigree (133 Piétrain sires and 266 crossbred dams) were weighed every 2 weeks and scored for physical abnormalities, such as lameness and ear and tail biting wounds (17,066 records). Resilience was assessed via deviations in body weight, deviations in weighing order and deviations in observed activity during weighing. The association between these resilience traits and physical abnormality traits was investigated and genetic parameters were estimated. Deviations in body weight had moderate heritability estimates (h2 = 25.2 to 36.3%), whereas deviations in weighing order (h2 = 4.2%) and deviations in activity during weighing (h2 = 12.0%) had low heritability estimates. Moreover, deviations in body weight were positively associated and genetically correlated with tail biting wounds (rg = 0.22 to 0.30), lameness (rg = 0.15 to 0.31) and mortality (rg = 0.19 to 0.33). These results indicate that events of tail biting, lameness and mortality are associated with deviations in pigs’ body weight evolution. This relationship was not found for deviations in weighing order and activity during weighing. Furthermore, individual body weight deviations were positively correlated with uniformity at the pen level, providing evidence that breeding for these resilience traits might increase both pigs’ resilience and within-family uniformity.ConclusionsIn summary, our findings show that breeding for resilience traits based on deviations in longitudinal weight data can decrease pigs’ tail biting wounds, lameness and mortality while improving uniformity at the pen level. These findings are valuable for pig breeders, as they offer evidence that these resilience traits are an indication of animals’ general health, welfare and resilience. Moreover, these results will stimulate the quantification of resilience via longitudinal body weights in other species.

A causal link between circulating leukocytes and three major urologic cancers: a mendelian randomization investigation.

This study aimed to explore the influence of serum leukocytes on urologic cancers (UC) using observation-based investigations. In the present study, Mendelian randomization (MR) was employed to assess the link between leukocyte count (LC) and the risk of UC development. Five LC and three major UC patient prognoses were obtained for MR analysis from genome-wide association studies (GWAS). Furthermore, in order to evaluate reverse causality, bidirectional studies were conducted. Finally, a sensitivity analysis using multiple methods was carried out. There was no significant correlation found in the genetic assessment of differential LC between the co-occurrence of bladder cancer (BCA) and renal cell carcinoma (RCC). Conversely, an individual 1-standard deviation (SD) rise in neutrophil count was strongly linked to a 9.3% elevation in prostate cancer (PCA) risk ([odd ratio]OR = 1.093, 95% [confidence interval]CI = 0.864-1.383, p = 0.002). Reverse MR analysis suggested that PCA was unlikely to cause changes in neutrophil count. Additional sensitivity studies revealed that the outcomes of all MR evaluations were similar, and there was no horizontal pleiotropy. Primary MR analysis using inverse-variance weighted (IVW) revealed that differential lymphocyte count significantly influenced RCC risk (OR = 1.162, 95%CI = 0.918-1.470, p = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904-1.725, p = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis. In summary, the results revealed that increased neutrophil counts represent a significant PCA risk factor. The current research indicates a significant relationship between immune cell activity and the cause of UC.

Heterogeneity of morphometric similarity networks in health and schizophrenia.

Morphometric similarity is a recently developed neuroimaging phenotype of inter-regional connectivity by quantifying the similarity of a region to other regions based on multiple MRI parameters. Altered average morphometric similarity has been reported in psychotic disorders at the group level, with considerable heterogeneity across individuals. We used normative modeling to address cross-sectional and longitudinal inter-individual heterogeneity of morphometric similarity in health and schizophrenia. Morphometric similarity for 62 cortical regions was obtained from baseline and follow-up T1-weighted scans of healthy individuals and patients with chronic schizophrenia. Cortical regions were classified into seven predefined brain functional networks. Using Bayesian Linear Regression and taking into account age, sex, image quality and scanner, we trained and validated normative models in healthy controls from eleven datasets (n = 4310). Individual deviations from the norm (z-scores) in morphometric similarity were computed for each participant for each network and region at both timepoints. A z-score ≧ than 1.96 was considered supra-normal and a z-score ≦ -1.96 infra-normal. As a longitudinal metric, we calculated the change over time of the total number of infra- or supra-normal regions per participant. At baseline, patients with schizophrenia had decreased morphometric similarity of the default mode network and increased morphometric similarity of the somatomotor network when compared with healthy controls. The percentage of patients with infra- or supra-normal values for any region at baseline and follow-up was low (<6%) and did not differ from healthy controls. Mean intra-group changes over time in the total number of infra- or supra-normal regions were small in schizophrenia and healthy control groups (<1) and there were no significant between-group differences. In a case-control setting, a decrease of morphometric similarity within the default mode network may be a robust finding implicated in schizophrenia. However, normative modeling suggests that significant reductions and changes over time of regional morphometric similarity are evident only in a minority of patients.

Repeatability of a Virtual Reality Headset Perimeter in Glaucoma and Ocular Hypertensive Patients.

The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability. Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests. Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67dB (95% confidence interval [CI], -6.04 to 4.71dB) and -0.15dB (95% CI, -8.04 to 7.73dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91). VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3months, except at the points around the blind spot and superiorly. The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.

Delineating the Heterogeneity of Alzheimer’s Disease and Mild Cognitive Impairment Using Normative Models of Dynamic Brain Functional Networks

BackgroundAlzheimer’s disease (AD), which has been identified as the most common type of dementia, presents considerable heterogeneity in its clinical manifestations. Early intervention at the stage of mild cognitive impairment (MCI) holds potential in AD prevention. However, characterizing the heterogeneity of neurobiological abnormalities and identifying MCI subtypes pose significant challenges. MethodsWe constructed sex-specific normative age models of dynamic brain functional networks and mapped the deviations of the brain characteristics for individuals from multiple datasets, including 295 patients with AD, 441 patients with MCI, and 1160 normal control participants. Then, based on these individual deviation patterns, subtypes for both AD and MCI were identified using the clustering method, and their similarities and differences were comprehensively assessed. ResultsIndividuals with AD and MCI were clustered into 2 subtypes, and these subtypes exhibited significant differences in their intrinsic brain functional phenotypes and spatial atrophy patterns, as well as in disease progression and cognitive decline trajectories. The subtypes with positive deviations in AD and MCI shared similar deviation patterns, as did those with negative deviations. There was a potential transformation of MCI with negative deviation patterns into AD, and participants with MCI had a more severe cognitive decline rate. ConclusionsIn this study, we quantified neurophysiological heterogeneity by analyzing deviation patterns from the dynamic functional connectome normative model and identified disease subtypes of AD and MCI using a comprehensive resting-state functional magnetic resonance imaging multicenter dataset. The findings provide new insights for developing early prevention and personalized treatment strategies for AD.

Characterizing the distinct imaging phenotypes, clinical behavior, and genetic vulnerability of brain maturational subtypes in mood disorders.

Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine. We recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort. Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable. Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.