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Journal of Computational and Graphical... 2024Large-scale observational health databases are increasingly popular for conducting comparative effectiveness and safety studies of medical products. However, increasing...
Large-scale observational health databases are increasingly popular for conducting comparative effectiveness and safety studies of medical products. However, increasing number of patients poses computational challenges when fitting survival regression models in such studies. In this paper, we use graphics processing units (GPUs) to parallelize the computational bottlenecks of massive sample-size survival analyses. Specifically, we develop and apply time- and memory-efficient single-pass parallel scan algorithms for Cox proportional hazards models and forward-backward parallel scan algorithms for Fine-Gray models for analysis with and without a competing risk using a cyclic coordinate descent optimization approach. We demonstrate that GPUs accelerate the computation of fitting these complex models in large databases by orders of magnitude as compared to traditional multi-core CPU parallelism. Our implementation enables efficient large-scale observational studies involving millions of patients and thousands of patient characteristics. The above implementation is available in the open-source R package Cyclops (Suchard et al., 2013).
PubMed: 38716090
DOI: 10.1080/10618600.2023.2213279 -
Disability and Rehabilitation 2015The study's purpose was to describe the range of knowledge pertaining to the Bobath (NDT) concept in adult neurological rehabilitation, synthesizes the findings,... (Review)
Review
OBJECTIVE
The study's purpose was to describe the range of knowledge pertaining to the Bobath (NDT) concept in adult neurological rehabilitation, synthesizes the findings, identify knowledge gaps and develop empirically based recommendations for future research.
METHODS
A scoping review of research and non-research articles published from 2007 to 2012. Two independent reviewers selected studies based on a systematic procedure. Inclusion criteria for studies were electronically accessible English language literature with Bobath and/or Neurodevelopmental Therapy as the subject heading in the title/keyword/abstract/intervention comparison with respect to adult neurological conditions. Data were abstracted and summarized with respect to study design, theoretical framework, clinical application including population representation, study fidelity, intervention comparison, duration of care, measurement and findings.
RESULTS
Of the 33 publications identified 17 were intervention studies (11 RCT's/1 prospective parallel group design/5 N-of-1). One other paper was a systematic review.
CONCLUSIONS
The intervention studies, primarily RCT designs, have serious methodological concerns particularly related to study/treatment fidelity and measurement resulting in no clear clinical direction. Aspects such as theoretical framework, therapist skill, quality of movement measurement and individualized interventions require careful consideration in the design of Bobath studies. Implications for Rehabilitation Future intervention studies should be based on the current Bobath theoretical framework and key aspects of clinical practice. Study and treatment fidelity issues need to be carefully considered when interpreting the results of existing RCT's evaluating the Bobath concept. N-of-1 randomized, observational, factorial and mixed method study designs should be considered as alternative study options.
Topics: Adult; Evidence-Based Practice; Humans; Knowledge; Neurological Rehabilitation; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Recovery of Function; Stroke Rehabilitation
PubMed: 25427891
DOI: 10.3109/09638288.2014.987880 -
Evolution Letters Apr 2019Adaptation often proceeds from standing variation, and natural selection acting on pairs of populations is a quantitative continuum ranging from parallel to divergent....
Adaptation often proceeds from standing variation, and natural selection acting on pairs of populations is a quantitative continuum ranging from parallel to divergent. Yet, it is unclear how the extent of parallel genetic evolution during adaptation from standing variation is affected by the difference in the direction of selection between populations. Nor is it clear whether the availability of standing variation for adaptation affects progress toward speciation in a manner that depends on the difference in the direction of selection. We conducted a theoretical study investigating these questions and have two primary findings. First, the extent of parallel genetic evolution between two populations rapidly declines as selection changes from fully parallel toward divergent, and this decline is steeper in organisms with more traits (i.e., greater dimensionality). This rapid decline happens because small differences in the direction of selection greatly reduce the fraction of alleles that are beneficial in both populations. For example, populations adapting to optima separated by an angle of 33° might have only 50% of potentially beneficial alleles in common. Second, relative to when adaptation is from only new mutation, adaptation from standing variation improves hybrid fitness under parallel selection and reduces hybrid fitness under divergent selection. Under parallel selection, genetic parallelism from standing variation reduces the phenotypic segregation variance in hybrids, thereby increasing mean fitness in the parental environment. Under divergent selection, larger pleiotropic effects of alleles fixed from standing variation cause maladaptive transgressive phenotypes when combined in hybrids. Adaptation from standing genetic variation therefore slows progress toward speciation under parallel selection and facilitates progress toward speciation under divergent selection.
PubMed: 31289688
DOI: 10.1002/evl3.106 -
GigaScience May 2020Several prediction problems in computational biology and genomic medicine are characterized by both big data as well as a high imbalance between examples to be learned,...
BACKGROUND
Several prediction problems in computational biology and genomic medicine are characterized by both big data as well as a high imbalance between examples to be learned, whereby positive examples can represent a tiny minority with respect to negative examples. For instance, deleterious or pathogenic variants are overwhelmed by the sea of neutral variants in the non-coding regions of the genome: thus, the prediction of deleterious variants is a challenging, highly imbalanced classification problem, and classical prediction tools fail to detect the rare pathogenic examples among the huge amount of neutral variants or undergo severe restrictions in managing big genomic data.
RESULTS
To overcome these limitations we propose parSMURF, a method that adopts a hyper-ensemble approach and oversampling and undersampling techniques to deal with imbalanced data, and parallel computational techniques to both manage big genomic data and substantially speed up the computation. The synergy between Bayesian optimization techniques and the parallel nature of parSMURF enables efficient and user-friendly automatic tuning of the hyper-parameters of the algorithm, and allows specific learning problems in genomic medicine to be easily fit. Moreover, by using MPI parallel and machine learning ensemble techniques, parSMURF can manage big data by partitioning them across the nodes of a high-performance computing cluster. Results with synthetic data and with single-nucleotide variants associated with Mendelian diseases and with genome-wide association study hits in the non-coding regions of the human genome, involhing millions of examples, show that parSMURF achieves state-of-the-art results and an 80-fold speed-up with respect to the sequential version.
CONCLUSIONS
parSMURF is a parallel machine learning tool that can be trained to learn different genomic problems, and its multiple levels of parallelization and high scalability allow us to efficiently fit problems characterized by big and imbalanced genomic data. The C++ OpenMP multi-core version tailored to a single workstation and the C++ MPI/OpenMP hybrid multi-core and multi-node parSMURF version tailored to a High Performance Computing cluster are both available at https://github.com/AnacletoLAB/parSMURF.
Topics: Algorithms; Computational Biology; Databases, Genetic; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Genomics; Humans; Machine Learning; Reproducibility of Results; Software
PubMed: 32444882
DOI: 10.1093/gigascience/giaa052 -
Biological Reviews of the Cambridge... May 2017The social environment modulates gene expression, physiology, behaviour and patterns of inheritance. For more than 50 years, this concept has been investigated using... (Review)
Review
The social environment modulates gene expression, physiology, behaviour and patterns of inheritance. For more than 50 years, this concept has been investigated using approaches that include partitioning the social component out of behavioural heritability estimates, studying maternal effects on offspring, and analysing dominance hierarchies. Recent advances have formalized this 'social environment effect' by providing a more nuanced approach to the study of social influences on behaviour while recognizing evolutionary implications. Yet, in most of these formulations, the dynamics of social interactions are not accounted for. Also, the reciprocity between individual behaviour and group-level interactions has been largely ignored. Consistent with evolutionary theory, the principles of social interaction are conserved across a broad range of taxa. While noting parallels in diverse organisms, this review uses Drosophila melanogaster as a case study to revisit what is known about social interaction paradigms. We highlight the benefits of integrating the history and pattern of interactions among individuals for dissecting molecular mechanisms that underlie social modulation of behaviour.
Topics: Animals; Biological Evolution; Drosophila melanogaster; Social Behavior; Social Dominance
PubMed: 26990016
DOI: 10.1111/brv.12267 -
Journal of Medical Education and... 2024We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident...
We created a serious game to teach first year anesthesiology (CA-1) residents to perform general anesthesia for cesarean delivery. We aimed to investigate resident knowledge gains after playing the game and having received one of 2 modalities of debriefing. We report on the development and validation of scores from parallel test forms for criterion-referenced interpretations of resident knowledge. The test forms were intended for use as pre- and posttests for the experiment. Validation of instruments measuring the study's primary outcome was considered essential for adding rigor to the planned experiment, to be able to trust the study's results. Parallel, multiple-choice test forms development steps included: (1) assessment purpose and population specification; (2) content domain specification and writing/selection of items; (3) content validation by experts of paired items by topic and cognitive level; and (4) empirical validation of scores from the parallel test forms using Classical Test Theory (CTT) techniques. Field testing involved online administration of 52 shuffled items from both test forms to 24 CA-1's, 21 second-year anesthesiology (CA-2) residents, 2 fellows, 1 attending anesthesiologist, and 1 of unknown rank at 3 US institutions. Items from each form yielded near-normal score distributions, with similar medians, ranges, and standard deviations. Evaluations of CTT item difficulty (item p values) and discrimination (D) indices indicated that most items met assumptions of criterion-referenced test design, separating experienced from novice residents. Experienced residents performed better on overall domain scores than novices ( < .05). Kuder-Richardson Formula 20 (KR-20) reliability estimates of both test forms were above the acceptability cut of .70, and parallel forms reliability estimate was high at .86, indicating results were consistent with theoretical expectations. Total scores of parallel test forms demonstrated item-level validity, strong internal consistency and parallel forms reliability, suggesting sufficient robustness for knowledge outcomes assessments of CA-1 residents.
PubMed: 38357687
DOI: 10.1177/23821205241229778 -
Genetics Jul 2021Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have...
Changes in gene regulation at multiple levels may comprise an important share of the molecular changes underlying adaptive evolution in nature. However, few studies have assayed within- and between-population variation in gene regulatory traits at a transcriptomic scale, and therefore inferences about the characteristics of adaptive regulatory changes have been elusive. Here, we assess quantitative trait differentiation in gene expression levels and alternative splicing (intron usage) between three closely related pairs of natural populations of Drosophila melanogaster from contrasting thermal environments that reflect three separate instances of cold tolerance evolution. The cold-adapted populations were known to show population genetic evidence for parallel evolution at the SNP level, and here we find evidence for parallel expression evolution between them, with stronger parallelism at larval and adult stages than for pupae. We also implement a flexible method to estimate cis- vs trans-encoded contributions to expression or splicing differences at the adult stage. The apparent contributions of cis- vs trans-regulation to adaptive evolution vary substantially among population pairs. While two of three population pairs show a greater enrichment of cis-regulatory differences among adaptation candidates, trans-regulatory differences are more likely to be implicated in parallel expression changes between population pairs. Genes with significant cis-effects are enriched for signals of elevated genetic differentiation between cold- and warm-adapted populations, suggesting that they are potential targets of local adaptation. These findings expand our knowledge of adaptive gene regulatory evolution and our ability to make inferences about this important and widespread process.
Topics: Acclimatization; Animals; Cold Temperature; Drosophila Proteins; Drosophila melanogaster; Evolution, Molecular; Models, Genetic
PubMed: 33989401
DOI: 10.1093/genetics/iyab077 -
The Journal of Physical Chemistry. A Jan 2023Heat-bath configuration interaction (HCI) is a deterministic method that approaches the full CI limit at greatly reduced computational cost. In this work, computational...
Heat-bath configuration interaction (HCI) is a deterministic method that approaches the full CI limit at greatly reduced computational cost. In this work, computational improvements to the HCI algorithm are introduced targeting speed, parallel efficiency, and memory requirements. The new implementation introduces a hash function to distribute determinants and takes advantage of MPI and OpenMP for parallelism allowing for a (22e,168o) active space to be studied, which explicitly includes 2.39 × 10 variational determinants and 8.95 × 10 perturbative determinants. Benchmarks show up to 86% parallel efficiency of the perturbative step on 32 nodes (4096 cores) and a total efficiency of 74%. The new HCI implementation is benchmarked for accuracy against prior results and applied to study the triplet-quintet gap in the challenging [FeO(NH)] complex.
Topics: Hot Temperature; Algorithms
PubMed: 36580361
DOI: 10.1021/acs.jpca.2c07949 -
Human Molecular Genetics Oct 2022Linkage disequilibrium and the incomplete regulatory annotation of the noncoding genome complicates the identification of functional noncoding genetic variants and their...
Linkage disequilibrium and the incomplete regulatory annotation of the noncoding genome complicates the identification of functional noncoding genetic variants and their causal association with disease. Current computational methods for variant prioritization have limited predictive value, necessitating the application of highly parallelized experimental assays to efficiently identify functional noncoding variation. Here, we summarize two distinct approaches, massively parallel reporter assays and CRISPR-based pooled screens and describe their flexible implementation to characterize human noncoding genetic variation at unprecedented scale. Each approach provides unique advantages and limitations, highlighting the importance of multimodal methodological integration. These multiplexed assays of variant effects are undoubtedly poised to play a key role in the experimental characterization of noncoding genetic risk, informing our understanding of the underlying mechanisms of disease-associated loci and the development of more robust predictive classification algorithms.
Topics: Humans; Genome; Genomics; Linkage Disequilibrium; Algorithms; Genome-Wide Association Study
PubMed: 36057282
DOI: 10.1093/hmg/ddac194 -
Chimia Apr 2023RNA splicing, the removal of introns and ligation of exons, is a crucial process during mRNA maturation. Group II introns are large ribozymes that self-catalyze their...
RNA splicing, the removal of introns and ligation of exons, is a crucial process during mRNA maturation. Group II introns are large ribozymes that self-catalyze their splicing, as well as their transposition. They are living fossils of spliceosomal introns and eukaryotic retroelements. The yeast mitochondrial Sc.ai5γ is the first identified and best-studied self-splicing group II intron. A combination of biochemical, biophysical, and computational tools enables studying its catalytic properties, structure, and dynamics, while also serving to develop new therapeutic and biotechnological tools. We survey the history of group II intron studies paralleling the trends in RNA methodology with Sc.ai5γ in the spotlight.
Topics: Introns; Biophysics; Biotechnology; Catalysis; Mitochondria
PubMed: 38047803
DOI: 10.2533/chimia.2023.235