Search

For neurological disorders and diseases, functional and anatomical connectomes of the human brain can be used to better inform targeted interventions and treatment strategies. Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique that captures spatio-temporal brain function through change in blood-oxygen-level-dependent (BOLD) signals over time. FMRI can be used to study the functional connectome through the functional connectivity matrix; that is, Pearson's correlation matrix between time series from the regions of interest of an fMRI image. One approach to analysing functional connectivity is using partial least squares (PLS), a multivariate regression technique designed for high-dimensional predictor data. However, analysing functional connectivity with PLS ignores a key property of the functional connectivity matrix; namely, these matrices are positive definite. To account for this, we introduce a generalisation of PLS to Riemannian manifolds, called R-PLS, and apply it to symmetric positive definite matrices with the affine invariant geometry. We apply R-PLS to two functional imaging datasets: COBRE, which investigates functional differences between schizophrenic patients and healthy controls, and; ABIDE, which compares people with autism spectrum disorder and neurotypical controls. Using the variable importance in the projection statistic on the results of R-PLS, we identify key functional connections in each dataset that are well represented in the literature. Given the generality of R-PLS, this method has the potential to investigate new functional connectomes in the brain, and with future application to structural data can open up further avenues of research in multi-modal imaging analysis., (© 2023. Springer Nature Limited.)

Background: There is increasing interest in the development and use of clinical prediction models, but a lack of evidence-supported guidance on the merits of different modelling approaches. This is especially true for time-to-event outcomes, where limited studies have compared the vast number of modelling approaches available. This study compares prediction accuracy and variable importance measures for four modelling approaches in prediction of time-to-revision surgery following total knee arthroplasty (TKA) and total hip arthroplasty (THA)., Methods: The study included 321,945 TKA and 151,113 THA procedures performed between 1 January 2003 and 31 December 2017. Accuracy of the Cox model, Weibull parametric model, flexible parametric model, and random survival forest were compared, with patient age, sex, comorbidities, and prosthesis characteristics considered as predictors. Prediction accuracy was assessed using the Index of Prediction Accuracy (IPA), c-index, and smoothed calibration curves. Variable importance rankings from the Cox model and random survival forest were also compared., Results: Overall, the Cox and flexible parametric survival models performed best for prediction of both TKA (integrated IPA 0.056 (95% CI [0.054, 0.057]) compared to 0.054 (95% CI [0.053, 0.056]) for the Weibull parametric model), and THA revision. (0.029 95% CI [0.027, 0.030] compared to 0.027 (95% CI [0.025, 0.028]) for the random survival forest). The c-index showed broadly similar discrimination between all modelling approaches. Models were generally well calibrated, but random survival forest underfitted the predicted risk of TKA revision compared to regression approaches. The most important predictors of revision were similar in the Cox model and random survival forest for TKA (age, opioid use, and patella resurfacing) and THA (femoral cement, depression, and opioid use)., Conclusion: The Cox and flexible parametric models had superior overall performance, although all approaches performed similarly. Notably, this study showed no benefit of a tuned random survival forest over regression models in this setting., (© 2022. The Author(s).)

Background: There is increasing interest in the development of statistical models that can be used to estimate risk of adverse patient outcomes after joint arthroplasty. Competing risk approaches have been recommended to estimate risk of longer-term revision, which is often likely to be precluded by the competing risk of death. However, a common approach is to ignore the competing risk by treating death as a censoring event and using standard survival models such as Cox regression. It is well-known that this approach can overestimate the event risk for population-level estimates, but the impact on the estimation of a patient's individualized risk after joint arthroplasty has not been explored., Questions/purposes: We performed this study to (1) determine whether using a competing risk or noncompeting risk method affects the accuracy of predictive models for joint arthroplasty revision and (2) determine the magnitude of difference that using a competing risks versus noncompeting risks approach will make to predicted risks for individual patients., Methods: The predictive performance of a standard Cox model, with competing risks treated as censoring events, was compared with the performance of two competing risks approaches, the cause-specific Cox model and Fine-Gray model. Models were trained and tested using data pertaining to 531,304 TKAs and 274,618 THAs recorded in the Australian Orthopaedic Association National Joint Replacement Registry between January 1, 2003 and December 31, 2017. The registry is a large database with near-complete capture and follow-up of all hip and knee joint arthroplasty in Australia from 2003 onwards, making it an ideal setting for this study. The performance of the three modeling approaches was compared in two different prediction settings: prediction of the 10-year risk of all-cause revision after TKA and prediction of revision for periprosthetic fracture after THA. The calibration and discrimination of each approach were compared using the concordance index, integrated Brier scores, and calibration plots. Calibration of 10-year risk estimates was further assessed within subgroups of age by comparing the observed and predicted proportion of events. Estimated 10-year risks from each model were also compared in three hypothetical patients with different risk profiles to determine whether differences in population-level performance metrics would translate into a meaningful difference for individual patient predictions., Results: The standard Cox and two competing risks models showed near-identical ability to distinguish between high-risk and low-risk patients (c-index 0.64 [95% CI, 0.64 to 0.64] for all three modeling approaches for TKAs and 0.66 [95% CI 0.66 to 0.66] for THA). All models performed similarly in patients younger than 75 years, but for patients aged 75 years and older, the standard Cox model overestimated the risk of revision more than the cause-specific Cox and Fine-Gray model did. These results were echoed when predictions were made for hypothetical individual patients. For patients with a low competing risk of mortality, the 10-year predicted risks from the standard Cox, cause-specific Cox, and Fine-Gray models were similar for TKAs and THAs. However, a larger difference was observed for hypothetical 89-year-old patients with increased mortality risk. In TKAs, the revision risk for an 89-year-old patient was so low that this difference was negligible (0.83% from the cause-specific Cox model versus 1.1% from the standard Cox model). However, for THAs, where older age is a risk factor for both death and revision for periprosthetic fracture, a larger difference was observed in the 10-year predicted risks for a hypothetical 89-year-old patient (3.4% from the cause-specific Cox model versus 5.2% from the standard Cox model)., Conclusion: When developing models to predict longer-term revision of joint arthroplasty, failing to use a competing risks modeling approach will result in overestimating the revision risk for patients with a high risk of mortality during the surveillance period. However, even in an extreme instance, where both the frequency of the event of interest and the competing risk of death are high, the largest absolute difference in predicted 10-year risk for an individual patient was just 1.8%, which may not be of consequence to an individual. Despite these findings, when developing or using risk prediction models, researchers and clinicians should be aware of how competing risks were handled in the modeling process, particularly if the model is intended for use populations where the mortality risk is high., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

One of the key technologies that lays behind the human-machine interaction and human motion diagnosis is the limbs motion tracking. To make the limbs tracking efficient, it must be able to estimate a precise and unambiguous position of each tracked human joint and resulting body part pose. In recent years, body pose estimation became very popular and broadly available for home users because of easy access to cheap tracking devices. Their robustness can be improved by different tracking modes data fusion. The paper defines the novel approach-orientation based data fusion-instead of dominating in literature position based approach, for two classes of tracking devices: depth sensors (i.e., Microsoft Kinect) and inertial measurement units (IMU). The detailed analysis of their working characteristics allowed to elaborate a new method that let fuse more precisely limbs orientation data from both devices and compensates their imprecisions. The paper presents the series of performed experiments that verified the method's accuracy. This novel approach allowed to outperform the precision of position-based joints tracking, the methods dominating in the literature, of up to 18%., Competing Interests: The authors declare no conflict of interest.

Background: We consider data from a time course microarray experiment that was conducted on grapevines over the development cycle of the grape berries at two different vineyards in South Australia. Although the underlying biological process of berry development is the same at both vineyards, there are differences in the timing of the development due to local conditions. We aim to align the data from the two vineyards to enable an integrated analysis of the gene expression and use the alignment of the expression profiles to classify likely developmental function., Results: We present a novel alignment method based on hidden Markov models (HMMs) and use the method to align the motivating grapevine data. We show that our alignment method is robust against subsets of profiles that are not suitable for alignment, investigate alignment diagnostics under the model and demonstrate the classification of developmentally driven genes., Conclusions: The classification of developmentally driven genes both validates that the alignment we obtain is meaningful and also gives new evidence that can be used to identify the role of genes with unknown function. Using our alignment methodology, we find at least 1279 grapevine probe sets with no current annotated function that are likely to be controlled in a developmental manner.

Motivation: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer-normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm., Results: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates., Availability: Data accession number SRA081939, code at http://code.google.com/p/snv-caller-review/, Contact: david.adelson@adelaide.edu.au, Supplementary Information: Supplementary data are available at Bioinformatics online.

"A central assumption in the standard capture-recapture approach to the estimation of the size of a closed population is the homogeneity of the 'capture' probabilities. In this article we develop an approach that allows for varying susceptibility to capture through individual parameters using a variant of the Rasch model from psychological measurement situations. Our approach requires an additional recapture. In the context of census undercount estimation, this requirement amounts to the use of a second independent sample or alternative data source to be matched with census and Post-Enumeration Survey (PES) data.... We illustrate [our] models and their estimation using data from a 1988 dress-rehearsal study for the 1990 census conducted by the U.S. Bureau of the Census, which explored the use of administrative data as a supplement to the PES. The article includes a discussion of extensions and related models.", (excerpt)

Patients who are considered for major pulmonary resection are normally evaluated by spirometry and clinical assessment. Despite this, the morbidity and mortality rates are high after these operations. We retrospectively reviewed results of lung resection performed during a period of 7.5 years in 237 patients to identify other important predictors of morbidity and mortality. There were 144 male and 93 female patients with a mean age of 59.4 +/- 11.4 years. The indication for operation was lung cancer in 199 (76 stage I, 34 stage II, 89 stage IIIA-B), benign disease in 34, and metastatic disease from other primary tumors in four. Lobectomy or bilobectomy was performed in 164 patients and pneumonectomy in 73. Data on 38 preoperative and operative risk factors were correlated with information on 24 postoperative events grouped into four major categories: death, pulmonary complications, cardiovascular complications, and other problems. Logistic regression analysis and chi 2 analysis were used to identify the relationship of the preoperative risk factors to the grouped postoperative complications. The diffusing capacity of the lung for carbon monoxide was the most important predictor of mortality (p less 0.01) and was the sole predictor of postoperative pulmonary complications (p less than 0.005). This diffusing capacity can reveal the existence of emphysematous changes in the lung, even when spirometric values are acceptable, and it usually should be a part of the evaluation of patients being considered for pulmonary resection.