Tag: statistics

Hum Brain Mapp. 2023 Mar 27. doi: 10.1002/hbm.26281. Online ahead of print.

ABSTRACT

Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy middle-aged and older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and other neuropsychological measures including flexibility. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in other aging-related functions. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.

PMID:36972323 | DOI:10.1002/hbm.26281

PLoS Comput Biol. 2023 Mar 27;19(3):e1010885. doi: 10.1371/journal.pcbi.1010885. Online ahead of print.

ABSTRACT

Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharacterised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.

PMID:36972311 | DOI:10.1371/journal.pcbi.1010885

PLoS Comput Biol. 2023 Mar 27;19(3):e1010994. doi: 10.1371/journal.pcbi.1010994. Online ahead of print.

ABSTRACT

We introduce a new spatial statistic, the weighted pair correlation function (wPCF). The wPCF extends the existing pair correlation function (PCF) and cross-PCF to describe spatial relationships between points marked with combinations of discrete and continuous labels. We validate its use through application to a new agent-based model (ABM) which simulates interactions between macrophages and tumour cells. These interactions are influenced by the spatial positions of the cells and by macrophage phenotype, a continuous variable that ranges from anti-tumour to pro-tumour. By varying model parameters that regulate macrophage phenotype, we show that the ABM exhibits behaviours which resemble the ‘three Es of cancer immunoediting’: Equilibrium, Escape, and Elimination. We use the wPCF to analyse synthetic images generated by the ABM. We show that the wPCF generates a ‘human readable’ statistical summary of where macrophages with different phenotypes are located relative to both blood vessels and tumour cells. We also define a distinct ‘PCF signature’ that characterises each of the three Es of immunoediting, by combining wPCF measurements with the cross-PCF describing interactions between vessels and tumour cells. By applying dimension reduction techniques to this signature, we identify its key features and train a support vector machine classifier to distinguish between simulation outputs based on their PCF signature. This proof-of-concept study shows how multiple spatial statistics can be combined to analyse the complex spatial features that the ABM generates, and to partition them into interpretable groups. The intricate spatial features produced by the ABM are similar to those generated by state-of-the-art multiplex imaging techniques which distinguish the spatial distribution and intensity of multiple biomarkers in biological tissue regions. Applying methods such as the wPCF to multiplex imaging data would exploit the continuous variation in biomarker intensities and generate more detailed characterisation of the spatial and phenotypic heterogeneity in tissue samples.

PMID:36972297 | DOI:10.1371/journal.pcbi.1010994

Br J Dermatol. 2023 Mar 27:ljad098. doi: 10.1093/bjd/ljad098. Online ahead of print.

ABSTRACT

BACKGROUND: Plaque psoriasis (PsO) is an inflammatory skin disease driven, in part, by the activation of Janus kinase (JAK) signalling pathways.

OBJECTIVE: To assess the efficacy and safety of multiple doses of topical brepocitinib, a tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO.

METHOD: This phase IIb, multicentre, randomised, double-blind study was conducted in two stages. In stage one, participants received one of eight treatments for 12 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. In stage two, participants received brepocitinib 3·0% BID or vehicle BID. The primary endpoint was the change from baseline in Psoriasis Area and Severity Index (PASI) score at week 12, analysed using analysis of covariance. The key secondary endpoint was the proportion of participants who achieved a Physician Global Assessment (PGA) response (score of clear (0) or almost clear (1) and an improvement of ≥2 points from baseline) at week 12. Additional secondary endpoints included the difference vs. vehicle in change from baseline in PASI, using mixed-model repeated measures (MMRM), and the change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) at week 12. Safety was monitored.

RESULTS: Overall, 344 participants were randomised. Topical brepocitinib did not result in statistically significant changes from respective vehicle controls in the primary or key secondary efficacy endpoints for any dose group. At week 12, least squares mean (LSM) change from baseline in PASI score ranged from -1·4 to -2·4 for brepocitinib QD groups vs. -1·6 for vehicle QD, and from -2·5 to -3·0 for brepocitinib BID groups vs. -2·2 for vehicle BID. From week 8, change from baseline in PASI score separated from vehicle in all brepocitinib BID groups. Brepocitinib was well-tolerated with AEs occurring at similar rates across groups. One participant in the brepocitinib 1·0% QD group developed a treatment-related AE of herpes zoster in the neck area.

CONCLUSION: Topical brepocitinib was well-tolerated but did not result in statistically significant changes vs. vehicle when administered at the doses evaluated to treat signs and symptoms of mild-to-moderate PsO.

CLINICALTRIALS.GOV IDENTIFIER: NCT03850483.

PMID:36972293 | DOI:10.1093/bjd/ljad098

J Basic Clin Physiol Pharmacol. 2023 Mar 27. doi: 10.1515/jbcpp-2023-0004. Online ahead of print.

ABSTRACT

OBJECTIVES: In preclinical research, etodolac, a non-steroidal anti-inflammatory drug, affected transient receptor potential ankyrin 1 (TRPA1) activation. Yet, whether the in vitro interaction between etodolac and TRPA1 translates to altered TRPA1 functionality in vivo in human remains to be investigated.

METHODS: A randomized, double-blinded, celecoxib-controlled study was conducted to assess the effect of etodolac on TRPA1-mediated dermal blood flow (DBF) changes on the forearm of 15 healthy, male volunteers aged between 18 and 45 years. Over four study visits, separated by at least five days wash-out, a single or four-fold dose of etodolac 200 mg or celecoxib 200 mg was administered orally. Two hours post-dose, TRPA1 functionality was evaluated by assessing cinnamaldehyde-induced DBF changes. DBF changes were quantified and expressed in Perfusion Units (PUs) using laser Doppler imaging during 60 min post-cinnamaldehyde application. The corresponding area under the curve (AUC_0-60min) was calculated as summary measure. Statistical analysis was performed using Linear mixed models with post-hoc Dunnett.

RESULTS: Neither the single dose of etodolac nor celecoxib inhibited the cinnamaldehyde-induced DBF changes compared to no treatment (AUC_0-60min ± SEM of 17,751 ± 1,514 PUs*min and 17,532 ± 1,706 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00). Similarly, also a four-fold dose of both compounds failed to inhibit the cinnamaldehyde-induced DBF changes (19,235 ± 1,260 PUs*min and 19,367 ± 1,085 PUs*min vs. 19,274 ± 1,031 PUs*min, respectively, both p=1.00).

CONCLUSIONS: Etodolac did not affect the cinnamaldehyde-induced DBF changes, suggesting that it does not alter TRPA1 functionality in vivo in human.

PMID:36972286 | DOI:10.1515/jbcpp-2023-0004

PLoS One. 2023 Mar 27;18(3):e0283654. doi: 10.1371/journal.pone.0283654. eCollection 2023.

ABSTRACT

The worldwide popularity of playing practices has led to a growing research interest in games’ impact on behavior and cognition. Many studies have already reported the benefits of both video games and board games for cognitive functions. However, these studies have mainly defined the term players according to a minimum play time or in connection to a specific game genre. No study has confronted the cognitive implications of video games and board games in the same statistical model. Thus, it remains unclear whether the cognitive benefits of play are due to play time or game type. To address this issue, in this study, we conducted an online experiment in which 496 participants completed six cognitive tests and a playing practice questionnaire. We examined the between the participants’ overall video game and board game play times and cognitive abilities. The results demonstrated significant relations between overall play time and all cognitive functions. Importantly, video games significantly predicted mental flexibility, planning, visual working memory, visuospatial processing, fluid intelligence, and verbal working memory performance, while board games were not found to predict any cognitive performance. These findings suggest that video games affect cognitive functions in specific ways compared to board games. We encourage further investigation to consider players’ individual differences through their play time and the specific features of the games they play.

PMID:36972271 | DOI:10.1371/journal.pone.0283654

PLoS One. 2023 Mar 27;18(3):e0283452. doi: 10.1371/journal.pone.0283452. eCollection 2023.

ABSTRACT

In this study, we attempt to anticipate annual rice production in Bangladesh (1961-2020) using both the Autoregressive Integrated Moving Average (ARIMA) and the eXtreme Gradient Boosting (XGBoost) methods and compare their respective performances. On the basis of the lowest Corrected Akaike Information Criteria (AICc) values, a significant ARIMA (0, 1, 1) model with drift was chosen based on the findings. The drift parameter value shows that the production of rice positively trends upward. Thus, the ARIMA (0, 1, 1) model with drift was found to be significant. On the other hand, the XGBoost model for time series data was developed by changing the tunning parameters frequently with the greatest result. The four prominent error measures, such as mean absolute error (MAE), mean percentage error (MPE), root mean square error (RMSE), and mean absolute percentage error (MAPE), were used to assess the predictive performance of each model. We found that the error measures of the XGBoost model in the test set were comparatively lower than those of the ARIMA model. Comparatively, the MAPE value of the test set of the XGBoost model (5.38%) was lower than that of the ARIMA model (7.23%), indicating that XGBoost performs better than ARIMA at predicting the annual rice production in Bangladesh. Hence, the XGBoost model performs better than the ARIMA model in predicting the annual rice production in Bangladesh. Therefore, based on the better performance, the study forecasted the annual rice production for the next 10 years using the XGBoost model. According to our predictions, the annual rice production in Bangladesh will vary from 57,850,318 tons in 2021 to 82,256,944 tons in 2030. The forecast indicated that the amount of rice produced annually in Bangladesh will increase in the years to come.

PMID:36972270 | DOI:10.1371/journal.pone.0283452

PLoS One. 2023 Mar 27;18(3):e0283686. doi: 10.1371/journal.pone.0283686. eCollection 2023.

ABSTRACT

While power shortages during and after a natural disaster cause severe impacts on response and recovery activities, related modeling and data collection efforts have been limited. In particular, no methodology exists to analyze long-term power shortages such as those that occurred during the Great East Japan Earthquake. To visualize a risk of supply shortage during a disaster and assist the coherent recovery of supply and demand systems, this study proposes an integrated damage and recovery estimation framework including the power generator, trunk distribution systems (over 154 kV), and power demand system. This framework is unique because it thoroughly investigates the vulnerability and resilience characteristics of power systems as well as businesses as primary power consumers observed in past disasters in Japan. These characteristics are essentially modeled by statistical functions, and a simple power supply-demand matching algorism is implemented using these functions. As a result, the proposed framework reproduces the original power supply and demand status from the 2011 Great East Japan Earthquake in a relatively consistent manner. Using stochastic components of the statistical functions, the average supply margin is estimated to be 4.1%, but the worst-case scenario is a 5.6% shortfall relative to peak demand. Thus, by applying the framework, the study improves knowledge on potential risk by examining a particular past disaster; the findings are expected to enhance risk perception and supply and demand preparedness after a future large-scale earthquake and tsunami disaster.

PMID:36972265 | DOI:10.1371/journal.pone.0283686

PLoS One. 2023 Mar 27;18(3):e0281665. doi: 10.1371/journal.pone.0281665. eCollection 2023.

ABSTRACT

Local production of generic medicines in developing countries has a critical role to meet public health needs by ensuring the availability of essential medicines and providing patients’ relief from the burden of unaffordable medical bills. Compliance with bioequivalence (BE) requirements increase the quality and competitiveness of generic drugs regardless of the source. In this regard, a regional BE center has been established in Addis Ababa, Ethiopia to serve the needs of Ethiopia and neighbouring countries. The present study aimed to assess the knowledge and perceptions of health professionals working in Addis Ababa regarding local production and BE studies of generic medicines. A cross-sectional survey was employed and physician participants working at public hospitals and pharmacists from various practice settings were selected using convenient sampling technique. Data was collected using self-administered structured questionnaire. Descriptive statistics was used to summarize the data and multinomial logistic regression analyses was used to assess predictors of health professionals’ perception towards the source of drugs. Statistically significant association was declared at p-value < 0.05. A total of 416 participants responded and 272 (65.4%) of them were male. Nearly half of the study participants (n = 194) preferred the imported products. Compared to physicians, participants with diploma (AOR = 0.40; 95%CI: 0.18-0.91, p = 0.028) and bachelor degree and above holders (AOR = 0.32; 95%CI: 0.15-0.68, p = 0.003) in pharmacy were more likely to prefer locally produced products. Participants who practiced in pharmaceutical industries (AOR = 0.40, 95%CI: 0.22-0.77, p = 0.006) preferred locally manufactured products as compared to those practicing in the hospital. While a majority (321, 77.2%) believed in the advantages of doing BE studies locally, only 106 (25.5%) recognized that local pharmaceutical manufacturers did not implement BE studies for their generic products and lack of enforcement by the national regulatory body was raised as a reason for not conducting BE studies by most of the participants (67.9%). The present study revealed a modest preference by physicians and pharmacy professionals towards locally produced products. Majority of participants supported the idea of doing BE studies locally. However, manufacturers and regulators should devise ways to increase health professionals’ confidence in local products. Strengthening local BE study capacity is also highly recommended.

PMID:36972261 | DOI:10.1371/journal.pone.0281665

Acad Med. 2023 Mar 22. doi: 10.1097/ACM.0000000000005215. Online ahead of print.

ABSTRACT

PURPOSE: Milestones have been used to assess trainees across graduate medical education programs and reflect a developmental continuum from novice to expert. This study examined whether residency milestones are correlated with initial fellowship milestone performance in pediatrics.

METHOD: This retrospective cohort study used descriptive statistics to assess milestone scores from pediatric fellows who began fellowship training between July 2017 and July 2020. Milestone scores were obtained at the end of residency (R), middle of the first fellowship year (F1), and end of the first fellowship year (F2).

RESULTS: Data represent 3,592 unique trainees. high composite R scores, much lower F1 scores, and slightly higher F2 scores were found over time for all pediatric subspecialities. R scores were positively correlated with F1 scores (Spearman ρ = 0.12, p < .001) and F2 scores (Spearman ρ = 0.15, p < .001). Although scores are negligibly different when trainees graduate from residency, there were differences in F1 and F2 scores among fellows in different specialties. Those who trained at the same institution for residency and fellowship had higher composite milestone F1 and F2 scores compared with those who trained at different institutions (p < .001). The strongest associations were between R and F2 scores for the professionalism and communication milestones, although associations were still relatively weak overall (rs = 0.13-0.20).

CONCLUSIONS: This study found high R scores and low F1 and F2 scores across all shared milestones, with weak association of scores within competencies, indicating that milestones are context dependent. Although professionalism and communication milestones had a higher correlation compared with the other competencies, the association was still weak. Residency milestones may be useful for individualized education in early fellowship, but fellowship programs should be cautious about overreliance on R scores due to the weak correlation with F1 and F2 scores.

PMID:36972134 | DOI:10.1097/ACM.0000000000005215