Early-childhood cytomegalovirus (CMV) infection and children’s neurocognitive development

2020 ◽  
Author(s):  
Samantha M Lee ◽  
Ruth Mitchell ◽  
Julia A Knight ◽  
Tony Mazzulli ◽  
Caroline Relton ◽  
...  
Keyword(s):  
Early Childhood ◽  
Reading Comprehension ◽  
Attentional Control ◽  
Large Scale ◽  
Bayes Factor ◽  
Population Based ◽  
General Intelligence ◽  
Cmv Infection ◽  
Level Of Evidence ◽  
Neurocognitive Outcomes

Abstract Background Despite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined. Methods CMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations. Results With adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35–4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43–2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13–2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12–3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection. Conclusion In this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.

Unravelling the knee-hip-spine trilemma from the CHECK study

2020 ◽  
Vol 102-B (9) ◽  
pp. 1261-1267
Author(s):  
Joost H. J. van Erp ◽  
Willem P. Gielis ◽  
Vahid Arbabi ◽  
Arthur de Gast ◽  
Harrie Weinans ◽  
...  
Keyword(s):  
Large Scale ◽  
Pelvic Incidence ◽  
Population Based ◽  
Disc Disease ◽  
Level Of Evidence ◽  
Knee Oa ◽  
Pelvic Morphology ◽  
Degenerative Disorders ◽  
Observational Cohort

Aims The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. Methods A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations. Results Demographic details were not different between the different PI groups. L4 to L5 and L5 to S1 spondylolisthesis were more frequently present in subjects with high PI compared to low PI (L4 to L5, OR 3.717; p = 0.024 vs L5 to S1 OR 7.751; p = 0.001). L5 to S1 DDD occurred more in patients with low PI compared to high PI (OR 1.889; p = 0.010), whereas there were no differences in L4 to L5 DDD among individuals with a different PI. The incidence of hip OA was higher in participants with low PI compared to normal (OR 1.262; p = 0.414) or high PI (OR 1.337; p = 0.274), but not statistically different. The incidence of knee OA was higher in individuals with a high PI compared to low PI (OR 1.620; p = 0.034). Conclusion High PI is a risk factor for development of spondylolisthesis and knee OA. Low pelvic incidence is related to DDD, and may be linked to OA of the hip. Level of Evidence: 1b Cite this article: Bone Joint J 2020;102-B(9):1261–1267.

Reaction-based Enumeration, Active Learning, and Free Energy Calculations to Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin Dependent Kinase 2 Inhibitors

2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Active Learning ◽  
Large Scale ◽  
Chemical Space ◽  
Population Based ◽  
Free Energy Calculations ◽  
Computational Technique ◽  
Cyclin Dependent Kinase ◽  
Energy Calculations

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.

Reaction-based Enumeration, Active Learning, and Free Energy Calculations to Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin Dependent Kinase 2 Inhibitors

2019 ◽  
Author(s):  
Kyle Konze ◽  
Pieter Bos ◽  
Markus Dahlgren ◽  
Karl Leswing ◽  
Ivan Tubert-Brohman ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Active Learning ◽  
Large Scale ◽  
Chemical Space ◽  
Population Based ◽  
Free Energy Calculations ◽  
Computational Technique ◽  
Cyclin Dependent Kinase ◽  
Energy Calculations

We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and cloud-based free energy calculations allows for large-scale potency predictions of compounds on a timescale that impacts drug discovery. The process is further accelerated by using a combination of population-based statistics and active learning techniques. Using this approach, we rapidly optimized R-groups and core hops for inhibitors of cyclin-dependent kinase 2. We explored greater than 300 thousand ideas and identified 35 ligands with diverse commercially available R-groups and a predicted IC<sub>50</sub> < 100 nM, and four unique cores with a predicted IC<sub>50</sub> < 100 nM. The rapid turnaround time, and scale of chemical exploration, suggests that this is a useful approach to accelerate the discovery of novel chemical matter in drug discovery campaigns.

scholarly journals Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

2021 ◽  
Author(s):  
Miguel Dasilva ◽  
Christian Brandt ◽  
Marc Alwin Gieselmann ◽  
Claudia Distler ◽  
Alexander Thiele
Keyword(s):  
Attentional Control ◽  
Large Scale ◽  
Neuronal Excitability ◽  
Cell Types ◽  
Receptor Activation ◽  
Frontal Eye Field ◽  
Control Signals ◽  
Cognitive Operations ◽  
Eye Field ◽  
Large Scale Networks

Abstract Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

scholarly journals Use of Antiplatelet Agents Decreases the Positive Predictive Value of Fecal Immunochemical Tests for Colorectal Cancer but Does Not Affect Their Sensitivity

2021 ◽  
Vol 11 (6) ◽  
pp. 497
Author(s):  
Yoonsuk Jung ◽  
Eui Im ◽  
Jinhee Lee ◽  
Hyeah Lee ◽  
Changmo Moon
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Screening Program ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Small Sample ◽  
Antithrombotic Agents ◽  
Predictive Values ◽  
Prescription Rates ◽  
Small Sample Sizes

Previous studies have evaluated the effects of antithrombotic agents on the performance of fecal immunochemical tests (FITs) for the detection of colorectal cancer (CRC), but the results were inconsistent and based on small sample sizes. We studied this topic using a large-scale population-based database. Using the Korean National Cancer Screening Program Database, we compared the performance of FITs for CRC detection between users and non-users of antiplatelet agents and warfarin. Non-users were matched according to age and sex. Among 5,426,469 eligible participants, 768,733 used antiplatelet agents (mono/dual/triple therapy, n = 701,683/63,211/3839), and 19,569 used warfarin, while 4,638,167 were non-users. Among antiplatelet agents, aspirin, clopidogrel, and cilostazol ranked first, second, and third, respectively, in terms of prescription rates. Users of antiplatelet agents (3.62% vs. 4.45%; relative risk (RR): 0.83; 95% confidence interval (CI): 0.78–0.88), aspirin (3.66% vs. 4.13%; RR: 0.90; 95% CI: 0.83–0.97), and clopidogrel (3.48% vs. 4.88%; RR: 0.72; 95% CI: 0.61–0.86) had lower positive predictive values (PPVs) for CRC detection than non-users. However, there were no significant differences in PPV between cilostazol vs. non-users and warfarin users vs. non-users. For PPV, the RR (users vs. non-users) for antiplatelet monotherapy was 0.86, while the RRs for dual and triple antiplatelet therapies (excluding cilostazol) were 0.67 and 0.22, respectively. For all antithrombotic agents, the sensitivity for CRC detection was not different between users and non-users. Use of antiplatelet agents, except cilostazol, may increase the false positives without improving the sensitivity of FITs for CRC detection.

scholarly journals Multi-GPU approach to global induction of classification trees for large-scale data mining

2021 ◽  
Author(s):  
Krzysztof Jurczuk ◽  
Marcin Czajkowski ◽  
Marek Kretowski
Keyword(s):  
Data Mining ◽  
Large Scale ◽  
Real Life ◽  
Population Based ◽  
Tree Structure ◽  
Global Approach ◽  
Data Parallel ◽  
Large Scale Data ◽  
The Impact ◽  
Scale Data

AbstractThis paper concerns the evolutionary induction of decision trees (DT) for large-scale data. Such a global approach is one of the alternatives to the top-down inducers. It searches for the tree structure and tests simultaneously and thus gives improvements in the prediction and size of resulting classifiers in many situations. However, it is the population-based and iterative approach that can be too computationally demanding to apply for big data mining directly. The paper demonstrates that this barrier can be overcome by smart distributed/parallel processing. Moreover, we ask the question whether the global approach can truly compete with the greedy systems for large-scale data. For this purpose, we propose a novel multi-GPU approach. It incorporates the knowledge of global DT induction and evolutionary algorithm parallelization together with efficient utilization of memory and computing GPU’s resources. The searches for the tree structure and tests are performed simultaneously on a CPU, while the fitness calculations are delegated to GPUs. Data-parallel decomposition strategy and CUDA framework are applied. Experimental validation is performed on both artificial and real-life datasets. In both cases, the obtained acceleration is very satisfactory. The solution is able to process even billions of instances in a few hours on a single workstation equipped with 4 GPUs. The impact of data characteristics (size and dimension) on convergence and speedup of the evolutionary search is also shown. When the number of GPUs grows, nearly linear scalability is observed what suggests that data size boundaries for evolutionary DT mining are fading.

scholarly journals Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322545
Author(s):  
Han-Mo Chiu ◽  
Grace Hsiao-Hsuan Jen ◽  
Ying-Wei Wang ◽  
Jean Ching-Yuan Fann ◽  
Chen-Yang Hsu ◽  
...  
Keyword(s):  
Large Scale ◽  
Distal Colon ◽  
Population Based ◽  
Proximal Colon ◽  
Advanced Stage ◽  
Site Specific ◽  
Faecal Immunochemical Test ◽  
Immunochemical Test ◽  
Selection Factors

ObjectiveTo measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.DesignA prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.ResultsFIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).ConclusionA large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.

Epidemiology of Acute Extensor Mechanism Injuries in Collegiate-Level Athletes in the United States

2021 ◽  
pp. 194173812110129
Author(s):  
Kevin K. Chen ◽  
Jimmy J. Chan ◽  
William Ranson ◽  
Nicholas Debellis ◽  
Hsin-Hui Huang ◽  
...  
Keyword(s):  
Large Scale ◽  
Injury Rate ◽  
Collegiate Athletes ◽  
The United States ◽  
Extensor Mechanism ◽  
Surveillance Program ◽  
Level Of Evidence ◽  
Severe Injuries ◽  
Male Athletes ◽  
Collegiate Level

Background: Extensor mechanism injuries involving the quadriceps tendon, patella, or patellar tendon can be a devastating setback for athletes. Despite the potential severity and relative frequency with which these injuries occur, large-scale epidemiological data on collegiate-level athletes are lacking. Study Design: Descriptive epidemiology study. Level of Evidence: Level 4. Methods: Knee extensor mechanism injuries across 16 sports among National Collegiate Athletic Association (NCAA) men and women during the 2004-2005 to 2013-2014 academic years were analyzed using the NCAA Injury Surveillance Program (NCAA-ISP). Extensor mechanism injuries per 100,000 athlete-exposures (AEs), operative rate, annual injury and reinjury rates, in-season status (pre-/regular/postseason), and time lost were compiled and calculated. Results: A total of 11,778,265 AEs were identified and included in the study. Overall, 1,748 extensor mechanism injuries were identified, with an injury rate (IR) of 14.84 (per 100,000 AEs). N = 114 (6.5%) injuries were classified as severe injuries with a relatively higher median time loss (44 days) and operative risk (18.42%). Male athletes had higher risk of season-ending injuries in both all (3.20% vs 0.89%, P < 0.01) and severe (41.54% vs 16.33%, P < 0.01) extensor mechanism injuries. Similarly, contact injuries were more frequently season-ending injuries (4.44% vs 1.69%, P = 0.01). Women’s soccer (IR = 2.59), women’s field hockey (IR = 2.15), and women’s cross country (IR = 2.14) were the sports with the highest rate of severe extensor mechanism injuries. Conclusion: Extensor mechanism injuries in collegiate athletes represent a significant set of injuries both in terms of volume and potentially to their athletic careers. Male athletes and contact injuries appear to have a greater risk of severe injuries. Injuries defined as severe had a higher risk of operative intervention and greater amount of missed playing time. Clinical Relevance: Knowledge of the epidemiology of extensor mechanism injuries may help clinicians guide their athlete patients in sports-related injury prevention and management.

scholarly journals Publisher Correction: A link between appendectomy and gastrointestinal cancers: a large-scale population-based cohort study in Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youn Young Park ◽  
Kil‑yong Lee ◽  
Seong Taek Oh ◽  
Sang Hyun Park ◽  
Kyung Do Han ◽  
...  
Keyword(s):  
Cohort Study ◽  
Large Scale ◽  
Population Based ◽  
Gastrointestinal Cancers ◽  
Scale Population

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Early Childhood Experiences and Kindergarten Success: A Population-Based Study of a Large Urban Setting

2005 ◽  
Vol 34 (4) ◽  
pp. 571-588 ◽  
Author(s):  
John W. Fantuzzo ◽  
Heather L. Rouse ◽  
Paul A. McDermott ◽  
Yumiko Sekino ◽  
Stephanie Childs ◽  
...  
Keyword(s):  
Early Childhood ◽  
Population Based ◽  
Urban Setting ◽  
Population Based Study ◽  
Childhood Experiences
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