multiple hypothesis testing
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2022 ◽  
Vol 12 (2) ◽  
pp. 880
Author(s):  
Yuvaraj Ramasamy ◽  
Viswanath Sundar ◽  
Juliana Usman ◽  
Rizal Razman ◽  
Harley Towler ◽  
...  

Three-dimensional position data of nineteen elite male Malaysian badminton players performing a series of maximal jump smashes were collected using a motion capture system. A ‘resultant moments’ inverse dynamics analysis was performed on the racket arm joints (shoulder, elbow and wrist). Relationships between racket head speed and peak joint moments were quantified using correlational analyses, inclusive of a Benjamini–Hochberg correction for multiple-hypothesis testing. The racket head centre speed at racket–shuttlecock contact was, on average, 61.2 m/s with a peak of 68.5 m/s which equated to average shuttlecock speeds of 95.2 m/s with a peak of 105.0 m/s. The correlational analysis revealed that a larger shoulder internal rotation moment (r = 0.737), backwards shoulder plane of elevation moment (r = 0.614) and wrist extension moment (r = −0.564) were associated with greater racket head centre speed at racket–shuttlecock contact. Coaches should consider strengthening the musculature associated with shoulder internal rotation, plane of elevation and wrist extension. This work provides a unique analysis of the joint moments of the racket arm during the badminton jump smash performed by an elite population and highlights significant relationships between racket head speed and peak resultant joint moments.


IEEE Access ◽  
2022 ◽  
pp. 1-1
Author(s):  
Jordi Perez-Guijarro ◽  
Alba Pages-Zamora ◽  
Javier Rodriguez Fonollosa

Author(s):  
Jennifer Fisher ◽  
Emma Jones ◽  
Victoria Flanary ◽  
Avery Williams ◽  
Elizabeth Ramsey ◽  
...  

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.


Author(s):  
Feng-Yuan Liu ◽  
Gigin Lin ◽  
Jing-Ren Tseng ◽  
Angel Chao ◽  
Huei-Jean Huang ◽  
...  

Abstract Purpose Heterogeneity assessment can be applied for medical imaging analysis. Here, we evaluated first-order and texture analysis (TA) metrics in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging for classification of metastatic and benign bone lesions in patients with cervical cancer. Methods The data of 18F-FDG PET studies performed on a specific PET/CT system from 2016 to 2018 in patients with cervical cancer were retrieved. The data of bone lesions extracted from studies over 2016–2017 and 2018 were used as training and validation datasets, respectively. Metastatic bone lesions were identified in each dataset, with an equal number of benign bone lesions selected. Cuboid volume of interest (VOI) consisting of 3 × 3 × 5 reconstructed voxels was applied for first-order metrics, and cubic VOI consisting of smaller voxels with trilinear interpolation of standardized uptake value (SUV) was adopted for TA metrics. First-order metrics included the maximum SUV (SUVmax) of lesions and the mean voxel SUV and its standard deviation (SUVsd), skewness, and kurtosis in VOI. In total, 4464 TA metrics based on 62 texture features were evaluated. Logistic regression was used for classification with area under the receiver operating characteristic curve (AUC) as the performance measure. Results From the training and validation datasets, 98 and 42 metastatic bone lesions were identified, respectively. SUVsd demonstrated higher performance than did SUVmax in both the training (AUC .798 vs .732, P = .001) and validation (AUC .786 vs .684, P < .001) datasets. Top-performing TA metrics demonstrated significantly higher performance in the training dataset, but not in the validation dataset. Conclusion A simple first-order measure of heterogeneity, SUVsd, was found to be superior to SUVmax for the classification of metastatic and benign bone lesions. Multiple hypothesis testing can result in false-positive findings in TA with multiple features and parameters; careful validation is required.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Patrick J Coppler ◽  
Clifton W CALLAWAY ◽  
Jonathan Elmer ◽  

Introduction: Patients resuscitated from out-of-hospital cardiac arrest (OHCA) have variable severity of brain injury. Signatures of severe injury on brain imaging and EEG including diffuse cerebral edema and burst suppression with identical bursts (BSIB). Current therapies for these patterns of injury are inadequate and patient outcomes are poor. Hypothesis: We hypothesize distinct phenotypes of brain injury are associated with increasing CPR duration. Methods: We identified from our prospective registry OHCA patients treated between January 2010 to July 2019. We abstracted CPR duration, best neurological examination < 6 hours from OHCA, initial brain CT grey-to-white ratio (GWR), and initial EEG pattern. We defined cerebral edema as GWR <1.20. We defined BSIB according to American Clinical Neurophysiology Society guidelines. We considered four phenotypes on presentation: awake; comatose with neither BSIB nor cerebral edema; BSIB; and cerebral edema. BSIB and cerebral edema were considered as non-mutually exclusive outcomes. We compared duration of CPR across groups using Kruskal-Wallis tests with Bonferroni correction for multiple hypothesis testing. We report the probability of presenting phenotype at the median CPR duration for each group using local regression. Results: We included 2,721 patients, of whom 582 (21%) were awake, 1,428 (52%) had coma without BSIB or edema, 372 (14%) had BSIB and 356 (13%) had cerebral edema. Only 47 (2%) had both BSIB and edema. Median CPR duration was 16 [IQR 8-28] minutes overall. Median CPR duration increased in a stepwise manner across groups: awake 6 [3-12] minutes; comatose without BSIB or edema 16 [9-27] minutes; BSIB 21 [14-30] minutes; cerebral edema 32 [22-46] minutes (all P <0.001). The probability of observing each phenotype at the median CPR duration for each was: awake (0.42); comatose without BSIB or edema (0.72); BSIB (0.34); cerebral edema (0.29). Conclusions: The brain injury phenotype is related to CPR duration, which is a surrogate for severity of ischemic injury. The sequence of most likely brain injury phenotype with progressively longer CPR duration is awake, coma without BSIB or edema, BSIB, and finally cerebral edema.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Franziska Meinck ◽  
Mark Orkin ◽  
Lucie Cluver

Abstract Background Adolescents experience a multitude of vulnerabilities which need to be addressed in order to achieve the Sustainable Development Goals (SDGs). In sub-Saharan Africa, adolescents experience high burden of HIV, violence exposure, poverty, and poor mental and physical health. This study aimed to identify interventions and circumstances associated with three or more targets (“accelerators”) within multiple SDGs relating to HIV-affected adolescents and examine cumulative effects on outcomes. Methods Prospective longitudinal data from 3401 adolescents from randomly selected census enumeration areas in two provinces with > 30% HIV prevalence carried out in 2010/11 and 2011/12 were used to examine six hypothesized accelerators (positive parenting, parental monitoring, free schooling, teacher support, food sufficiency and HIV-negative/asymptomatic caregiver) targeting twelve outcomes across four SDGs, using a multivariate (multiple outcome) path model with correlated outcomes controlling for outcome at baseline and socio-demographics. The study corrected for multiple-hypothesis testing and tested measurement invariance across sex. Percentage predicted probabilities of occurrence of the outcome in the presence of the significant accelerators were also calculated. Results Sample mean age was 13.7 years at baseline, 56.6% were female. Positive parenting, parental monitoring, food sufficiency and AIDS-free caregiver were variously associated with reductions on ten outcomes. The model was gender invariant. AIDS-free caregiver was associated with the largest reductions. Combinations of accelerators resulted in a percentage reduction of risk of up to 40%. Conclusion Positive parenting, parental monitoring, food sufficiency and AIDS-free caregivers by themselves and in combination improve adolescent outcomes across ten SDG targets. These could translate to the corresponding real-world interventions parenting programmes, cash transfers and universal access to antiretroviral treatment, which when provided together, may help governments in sub-Saharan Africa more economically to reach their SDG targets.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12415
Author(s):  
Punit Tyagi ◽  
Mangesh Bhide

Background In the past decade, RNA sequencing and mass spectrometry based quantitative approaches are being used commonly to identify the differentially expressed biomarkers in different biological conditions. Data generated from these approaches come in different sizes (e.g., count matrix, normalized list of differentially expressed biomarkers, etc.) and shapes (e.g., sequences, spectral data, etc.). The list of differentially expressed biomarkers is used for functional interpretation and retrieve biological meaning, however, it requires moderate computational skills. Thus, researchers with no programming expertise find difficulty in data interpretation. Several bioinformatics tools are available to analyze such data; however, they are less flexible for performing the multiple steps of visualization and functional interpretation. Implementation We developed an easy-to-use Shiny based web application (named as OMnalysis) that provides users with a single platform to analyze and visualize the differentially expressed data. The OMnalysis accepts the data in tabular form from edgeR, DESeq2, MaxQuant Perseus, R packages, and other similar software, which typically contains the list of differentially expressed genes or proteins, log of the fold change, log of the count per million, the P value, q-value, etc. The key features of the OMnalysis are multiple image type visualization and their dimension customization options, seven multiple hypothesis testing correction methods to get more significant gene ontology, network topology-based pathway analysis, and multiple databases support (KEGG, Reactome, PANTHER, biocarta, NCI-Nature Pathway Interaction Database PharmGKB and STRINGdb) for extensive pathway enrichment analysis. OMnalysis also fetches the literature information from PubMed to provide supportive evidence to the biomarkers identified in the analysis. In a nutshell, we present the OMnalysis as a well-organized user interface, supported by peer-reviewed R packages with updated databases for quick interpretation of the differential transcriptomics and proteomics data to biological meaning. Availability The OMnalysis codes are entirely written in R language and freely available at https://github.com/Punit201016/OMnalysis. OMnalysis can also be accessed from - http://lbmi.uvlf.sk/omnalysis.html. OMnalysis is hosted on a Shiny server at https://omnalysis.shinyapps.io/OMnalysis/. The minimum system requirements are: 4 gigabytes of RAM, i3 processor (or equivalent). It is compatible with any operating system (windows, Linux or Mac). The OMnalysis is heavily tested on Chrome web browsers; thus, Chrome is the preferred browser. OMnalysis works on Firefox and Safari.


2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e80-e81
Author(s):  
Michelle Schneeweiss ◽  
Caroline Reid-Westoby ◽  
George Hu ◽  
Molly Pottruff ◽  
Magdalena Janus

Abstract Primary Subject area Epidemiology Background Asthma, the most common chronic illness affecting Canadian youth, can profoundly and adversely impact a child’s quality of life. Previous studies have shown a diagnosis of asthma can influence a child’s physical and socio-emotional functioning. Current data on asthma prevalence rates among Canadian children is scarce, and it is still unclear how this diagnosis impacts their development at school entry. Objectives The goals of the current study were to 1) examine the prevalence of teacher-reported asthma in Canadian kindergarten children, and 2) investigate the association between asthma and children’s concurrent developmental health. Design/Methods A cross sectional, population-level study of kindergarten children diagnosed with asthma as reported on the Early Development Instrument (EDI), was carried out in Canada from 2010-2015. Children’s developmental health in kindergarten was measured with the EDI. This 103-item questionnaire is completed by teachers for their students aged 4-6 years and covers demographic information, as well as five different domains of development. Descriptive statistics were examined for children with and without asthma. The level of statistical significance was adjusted using a Bonferroni correction to account for multiple hypothesis testing. The chi-square and one-way ANOVA statistics, as well as effect sizes (Cramer’s V, and eta squared) were reported for all descriptive analyses. Results 958 children (0.002% of the final analytical sample) were identified as having a teacher-reported diagnosis of asthma. Compared to their peers, children with asthma were significantly more likely to: be male (68.2% vs 51.2%); have a special needs designation (19.0% vs 3.6%); have a functional impairment (53.5% vs 15.9%); be identified by their teachers as needing further developmental assessment (32.3% vs. 13.1%); and miss, on average, 3 more days of school than their peers (9.44 vs. 6.71). They were also more likely to fall below a vulnerability threshold on one or more of the developmental domains (55.9% vs. 28.8%, Figure 1). Conclusion It is likely that the EDI captures only severe cases of asthma, as parents are more likely to disclose their child’s illness to teachers if it may influence their ability to function in a classroom. As such, children with asthma, especially those with severe forms, may require additional support. A partnership in which physicians provide preventative care, and teachers provide academic and classroom assistance, may help to ensure the optimal development of children with asthma, and close gaps between them and their peers.


Author(s):  
Sanjay Sinha ◽  
Lavina Matina

Background: Knowledge regarding lower urinary tract function in adult men could help in making informed choices. Few studies have examined the entire spectrum of adult males. Methods: This is a retrospective analysis of all adult men with refractory non-neurogenic urinary symptoms presenting to a tertiary center over 9 years. International Continence Society defined indices bladder outlet obstruction index (BOOI) and bladder contractility index (BCI) were calculated with established classification. Storage abnormality was defined as presence of detrusor overactivity, poor compliance (< 20mL per cm H20) or both. Data were analyzed by non-parametric tests using SPSS (version 20.0.0, Armonk NY ) (P < 0.05 significant; 2-tailed). Where appropriate, correction for multiple hypothesis testing was applied. Results: A total of 1596 men (range 18 to 91 years, median 51.0 years; IQR 34 to 64 years) were eligible. Median BCI and BOOI were 99.5 and 37.0, respectively, and a storage abnormality was noted in 41.7%. On multivariate analysis, age was significantly associated with urodynamic findings. While not strictly linear, for each 10 years increase in age, on average, the BCI fell 2.4 points and the BOOI increased by 2.4 points. Increasing age was also associated with increasing odds of finding a storage abnormality (OR 1.015; 95%CI 1.008 to 1.022; P < 0.001). On post hoc analysis (Bonferroni correction), men under 30 years were least likely of any group to show obstruction (30.3%; median BOOI 26). Conclusions: Adult men with refractory urinary symptoms show age-associated differences in urodynamic findings. An awareness of these trends can help take more informed decisions in clinical care.


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