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Nevin Manimala Statistics

Sample size justifications in Gait & Posture

Gait Posture. 2021 Dec 11;92:333-337. doi: 10.1016/j.gaitpost.2021.12.010. Online ahead of print.

ABSTRACT

BACKGROUND: Context regarding how researchers determine the sample size of their experiments is important for interpreting the results and determining their value and meaning. Between 2018 and 2019, the journal Gait & Posture introduced a requirement for sample size justification in their author guidelines.

RESEARCH QUESTION: How frequently and in what ways are sample sizes justified in Gait & Posture research articles and was the inclusion of a guideline requiring sample size justification associated with a change in practice?

METHODS: The guideline was not in place prior to May 2018 and was in place from 25th July 2019. All articles in the three most recent volumes of the journal (84-86) and the three most recent, pre-guideline volumes (60-62) at time of preregistration were included in this analysis. This provided an initial sample of 324 articles (176 pre-guideline and 148 post-guideline). Articles were screened by two authors to extract author data, article metadata and sample size justification data. Specifically, screeners identified if (yes or no) and how sample sizes were justified. Six potential justification types (Measure Entire Population, Resource Constraints, Accuracy, A priori Power Analysis, Heuristics, No Justification) and an additional option of Other/Unsure/Unclear were used.

RESULTS: In most cases, authors of Gait & Posture articles did not provide a justification for their study’s sample size. The inclusion of the guideline was associated with a modest increase in the percentage of articles providing a justification (16.6-28.1%). A priori power calculations were the dominant type of justification, but many were not reported in enough detail to allow replication.

SIGNIFICANCE: Gait & Posture researchers should be more transparent in how they determine their sample sizes and carefully consider if they are suitable. Editors and journals may consider adding a similar guideline as a low-resource way to improve sample size justification reporting.

PMID:34920357 | DOI:10.1016/j.gaitpost.2021.12.010

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Prediction of degradability of micropollutants by sonolysis in water with QSPR – a case study on phenol derivates

Ultrason Sonochem. 2021 Dec 8;82:105867. doi: 10.1016/j.ultsonch.2021.105867. Online ahead of print.

ABSTRACT

The increasing quantity and variety of organic contaminants discharged into surface and groundwater increase the necessity of additional and suitable water treatment methods, which can be incorporated into existing wastewater treatment plants. The huge variety of micropollutants and local variability of the composition of the organic load or matrix effects paired with multiple possible degradation processes lead to the requirement of a recommendation tool for the best possible water treatment method under given local conditions. Due to the diversity of physicochemical properties of micropollutants, such predictions are challenging. In this study, a quantitative correlation between the structural properties of certain micropollutants and their degradability using high-frequency sonolysis has been investigated. Therefore, Quantitative Structure-Property Relationship (QSPR) has been applied on a set of phenol derivates. To obtain the kinetic data, all experiments have been conducted in standardized, constant conditions for all 32 investigated phenol derivates. QSPR modelling was then executed using the software PaDEL for descriptor calculation and the software QSARINS for the overall modelling process including genetic algorithm (GA) and multiple linear regression (MLR). The final model consisting of 5 molecular descriptors was selected using a multi-criteria decision-making method based on extensive statistical parameters. The predictive power and robustness of the model was evaluated by means of internal cross validation and external validation using an independent validation set. The final selected model showed very good values for regression abilities, predictive power as well as stability (R2adj = 0.9455, CCCtr = 0.9777, Q2loo = 0.9285, CCCext = 0.9797 and Q2ext-F1 = 0.9711). The applicability domain of the QSPR model was defined based on the Williams plot and Insubria plot. The five OECD principles for the application of QSPR/QSAR modelling in industry and regulation were fulfilled in the whole process to the best of our knowledge, including the collection of the underlying experimental data as well as the entire modelling process. The final QSPR model included the molecular polarity and occurrence of hydrogen bonds as major influences on the reaction rate constants in accordance with previous studies. Nevertheless, potential biases in the selection of these descriptors due to the small size of the dataset were highlighted.

PMID:34920352 | DOI:10.1016/j.ultsonch.2021.105867

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Unravelling direct and indirect contact patterns between duck farms in France and their association with the 2016-2017 epidemic of Highly Pathogenic Avian Influenza (H5N8)

Prev Vet Med. 2021 Nov 23;198:105548. doi: 10.1016/j.prevetmed.2021.105548. Online ahead of print.

ABSTRACT

Live animal movements generate direct contacts (via the exchange of live animals) and indirect contacts (via the transit of transport vehicles) between farms, which can contribute to the spread of pathogens. However, most analyses focus solely on direct contacts and can therefore underestimate the contribution of live animal movements in the spread of infectious diseases. Here, we used French live duck movement data (2016-2018) from one of the largest transport companies to compare direct and indirect contact patterns between duck farms and evaluate how these patterns were associated with the French 2016-2017 epidemic of highly pathogenic avian influenza H5N8. A total number of 614 farms were included in the study, and two directed networks were generated: the animal introduction network (exchange of live ducks) and the transit network (transit of transport vehicles). Following descriptive analyses, these two networks were scrutinized in relation to farm infection status during the epidemic. Results showed that farms were substantially more connected in the transit network than in the animal introduction network and that the transit of transport vehicles generated more opportunities for transmission than the exchange of live animals. We also showed that animal introduction and transit networks’ statistics decreased substantially during the epidemic (January-March 2017) compared to non-epidemic periods (January-March 2016 and January-March 2018). We estimated a probability of 33.3 % that a farm exposed to the infection through either of the two live duck movement networks (i.e. that was in direct or indirect contact with a farm that was reported as infected in the following seven days) becomes infected within seven days after the contact. However, we also demonstrated that the level of exposure of farms by these two contact patterns was low, leading only to a handful of transmission events through these routes. As a consequence, we showed that live animal movement patterns are efficient transmission routes for HPAI but have been efficiently reduced to limit the spread during the French 2020-2021 epidemic. These results underpin the relevance of studying indirect contacts resulting from the movement of animals to understand their transmission potential and the importance of accounting for both routes when designing disease control strategies.

PMID:34920326 | DOI:10.1016/j.prevetmed.2021.105548

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The influence of social determinants of health on epilepsy treatment delays in an Arizona Medicaid population

Epilepsy Behav. 2021 Dec 14;126:108473. doi: 10.1016/j.yebeh.2021.108473. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to better understand the role of social determinants of health (SDoH) in both treatment delays and treatment gaps for individuals with epilepsy (IWE) enrolled in Arizona’s Medicaid program using predictive models at the population and individual levels.

METHODS: In this retrospective cohort study, two statistical regression models were developed using Arizona Medicaid medical and pharmacy claims records from 2015-2019 and selected census tract-level SDoH data. Three treatment outcomes were defined: timely treatment (treated within thirty days); delayed treatment (treated after thirty days); and untreated. For the first model, least squares regression was used to regress the epilepsy treatment delays on selected SDoH factors at the population-level. For the second model, multinomial logistic regression was used to estimate associations between epilepsy treatment delays and individual-level sociodemographic factors.

RESULTS: Of the 5965 IWE identified with a new epilepsy diagnosis during the study period, 43.1% were treated with a mean delay of 180 days. Among the treated population, 42% received timely treatment. A treatment gap of at least 40.6% and potentially up to 56.9% was calculated. Individuals with epilepsy diagnosed in an inpatient setting or in emergency departments were more likely to be treated and receive timely treatment than those diagnosed in an office or clinic setting. Individuals with epilepsy diagnosed in “other” settings were more likely to go untreated or receive delayed treatment than a patient diagnosed in an office or clinic. Compared to IWE aged 31-50 years, IWE aged 0-30 years were more likely to receive timely treatment, IWE aged 51-64 years were more likely to receive delayed treatment, and IWE aged 65 years or older were more likely to go untreated. Widowed IWE were more likely to go untreated relative to single patients. Individuals with epilepsy experiencing homelessness were also more likely to go untreated. Unemployed IWE were more likely to go untreated or receive delayed treatment. Native American IWE were more likely to go untreated compared to White patients.

CONCLUSIONS: Treatment gaps and treatment delays are experienced by IWE in the Arizona Medicaid population. The SDoH factors predicted to impact treatment delays include care setting, age, race, marital status, homelessness, and employment.

PMID:34920347 | DOI:10.1016/j.yebeh.2021.108473

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A hyperelastic model to capture the mechanical behaviour and histological aspects of the soft tissues

J Mech Behav Biomed Mater. 2021 Dec 3;126:105013. doi: 10.1016/j.jmbbm.2021.105013. Online ahead of print.

ABSTRACT

It is well established that the soft connective tissues show a nonlinear elastic response that comes from their microstructural arrangement. Tissues’ microstructure alters with various physiological conditions and may affect their mechanical responses. Therefore, the accurate prediction of tissue’s mechanical response is crucial for clinical diagnosis and treatments. Thus, a physically motivated and mathematically simplified model is required for the accurate prediction of tissues’ mechanical and structural responses. This study explored the ‘Exp-Ln’ hyperelastic model (Khajehsaeid et al., 2013) to capture soft tissues’ mechanical and histological behaviour. In this work, uniaxial tensile test data for the belly and back pig skin were extracted from the experiments performed in our laboratory, whereas uniaxial test data for other soft tissues (human skin, tendon, ligament, and aorta) were extracted from the literature. The ‘Exp-Ln; and other hyperelastic models (e.g. Money Rivlin, Ogden, Yeoh, and Gent models) were fitted with these experimental data, and obtained results were compared between the models. These results show that the ‘Exp-Ln’ model could capture the mechanical behaviour of soft tissues more accurately than other hyperelastic models. This model was also found numerically stable for all modes and ranges of deformation. This study also investigated the link between ‘Exp-Ln’ material parameters and tissue’s histological parameters. The histological parameters such as collagen content, fibre free length, crosslink density, and collagen arrangement were measured using staining and ATR-FTIR techniques. The material parameters were found statistically correlated with the histological parameters. Further, ‘Exp-Ln’ model was implemented in ABAQUS through the VUMAT subroutine, where the mechanical behaviour of various soft tissues was simulated for different modes of deformation. The finite element analysis results obtained using the ‘Exp-Ln’ model agreed with the experiments and were more accurate than other hyperelastic models. Overall, these results demonstrate the capability of ‘Exp-Ln’ model to predict the mechanical and structural responses of the soft tissues.

PMID:34920323 | DOI:10.1016/j.jmbbm.2021.105013

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ONEST (Observers Needed to Evaluate Subjective Tests) suggests four or more observers for a reliable assessment of the consistency of histological grading of invasive breast carcinoma: A reproducibility study with a retrospective view on previous studies

Pathol Res Pract. 2021 Dec 6;229:153718. doi: 10.1016/j.prp.2021.153718. Online ahead of print.

ABSTRACT

Histological grade is one of the most important prognosticators of breast cancer which is available for nearly all cases. It also makes part of several multivariable analysis derived combined prognostic profiles despite concerns about its reproducibility. The aims included a reproducibility study of grading in the light of a recently described statistical approach, ONEST (Observers Needed to Evaluate Subjective Tests) and review earlier reproducibility studies in the light of the ONEST analysis. Nine pathologists reviewed 50 core needle biopsies and 50 slides from different excision specimens and recorded the scores for gland (tubule) formation, nuclear pleomorphism and mitotic activity as well as histological grade. Overall percent agreement, Fleiss kappa and the intraclass correlation coefficient (ICC) were used for the analysis of reproducibility. ONEST data and curves were generated from 100 random permutations of the participants. ONEST suggested a minimum of 4 observers for the reliable evaluation of reproducibility for both the scored components and grade in either type of specimen. Our results suggested moderate or moderate to good reproducibility of grading (kappa values of 0.51 for excisions, and 0.54 for biopsies and ICCs of 0.70 and 0.69, respectively) with gland formation being the most and nuclear pleomorphism the worst consistently evaluated feature. In studies with sufficient participants (at least 4) and non-pairwise comparisons in the analysis, the reproducibility of histological grading is fair to moderate, whereas studies with fewer participants or pairwise kappa analysis suggest moderate to almost prefect agreement of the results. ONEST is a valuable complementation of reproducibility analyses.

PMID:34920295 | DOI:10.1016/j.prp.2021.153718

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Does morphological complexity affect word segmentation? Evidence from computational modeling

Cognition. 2021 Dec 14;220:104960. doi: 10.1016/j.cognition.2021.104960. Online ahead of print.

ABSTRACT

How can infants detect where words or morphemes start and end in the continuous stream of speech? Previous computational studies have investigated this question mainly for English, where morpheme and word boundaries are often isomorphic. Yet in many languages, words are often multimorphemic, such that word and morpheme boundaries do not align. Our study employed corpora of two languages that differ in the complexity of inflectional morphology, Chintang (Sino-Tibetan) and Japanese (in Experiment 1), as well as corpora of artificial languages ranging in morphological complexity, as measured by the ratio and distribution of morphemes per word (in Experiments 2 and 3). We used two baselines and three conceptually diverse word segmentation algorithms, two of which rely purely on sublexical information using distributional cues, and one that builds a lexicon. The algorithms’ performance was evaluated on both word- and morpheme-level representations of the corpora. Segmentation results were better for the morphologically simpler languages than for the morphologically more complex languages, in line with the hypothesis that languages with greater inflectional complexity could be more difficult to segment into words. We further show that the effect of morphological complexity is relatively small, compared to that of algorithm and evaluation level. We therefore recommend that infant researchers look for signatures of the different segmentation algorithms and strategies, before looking for differences in infant segmentation landmarks across languages varying in complexity.

PMID:34920298 | DOI:10.1016/j.cognition.2021.104960

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Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management

ESMO Open. 2021 Dec 14;7(1):100338. doi: 10.1016/j.esmoop.2021.100338. Online ahead of print.

ABSTRACT

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population.

PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs.

RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001).

CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

PMID:34920290 | DOI:10.1016/j.esmoop.2021.100338

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Assessment of susceptibility to phthalate and DINCH exposure through CYP and UGT single nucleotide polymorphisms

Environ Int. 2021 Dec 14;159:107046. doi: 10.1016/j.envint.2021.107046. Online ahead of print.

ABSTRACT

Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase (UGTs) genes have been proposed to influence phthalates and 1,2-cyclo-hexanedicarboxylic acid diisononyl ester (DINCH) biotransformation but have not been investigated on a populational level. We investigated the role of SNPs in CYP2C9, CYP2C19, CYP2D6, UGT2B15, and UGT1A7 genes in the biotransformation of phthalates (DEHP, DEP, DiBP, DnBP, BBzP, DiNP, DidP) and DINCH by determining their urine metabolites. From the Slovenian study population of 274 men and 289 lactating primiparous women we obtained data on phthalate and DINCH urine metabolite levels (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MEP, MiBP, MnBP, MBzP, cx-MINP, OH-MiDP, MCHP, MnPeP, MnOP, 5OH-MINCH, 5oxo-MINCH), SNP genotypes (rs1057910 = CYP2C9*3, rs1799853 = CYP2C9*2, rs4244285 = CYP2C19*2, rs12248560 = CYP2C19*17, rs3892097 = CYP2D6*4, rs1902023 = UGT2B15*2, and rs11692021 = UGT1A7*3) and questionnaires. Associations of SNPs with levels of metabolites and their ratios were assessed by multiple linear regression and ordinary logistic regression analyses. Significant associations were observed for CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs. The most pronounced was the influence of CYP2C9*2 and *3 on the reduced DEHP biotransformation, with lower levels of metabolites and their ratios in men and women. In contrast, carriers of CYP2C19*17 showed higher urine levels of DEHP metabolites in both genders, and in women also in higher DiNP, DiDP, and DINCH metabolite levels. The presence of UGT1A7*3 was associated with increased metabolite levels of DINCH in men and of DiBP and DBzP in women. Statistical models explained up to 27% of variability in metabolite levels or their ratios. Our observations confirm the effect of CYP2C9*2 and *3 SNPs towards reduced DEHP biotransformation. We show that CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs might represent biomarkers of susceptibility or resilience in phthalates and DINCH exposure that have been so far unrecognised.

PMID:34920277 | DOI:10.1016/j.envint.2021.107046

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Degradation of chlorinated volatile organic compounds from contaminated ground water using a carrier-bound TiO2/UV/O3-system

J Environ Manage. 2021 Dec 14;304:114236. doi: 10.1016/j.jenvman.2021.114236. Online ahead of print.

ABSTRACT

In the present work, a suitable experimental setup was developed to successfully apply advanced oxidation processes (AOP) to real groundwater matrices. This setup combines an O3-bubble column reactor with a carrier-bound TiO2/UV-system. The degradation of various chlorinated ethene and methane derivatives commonly found of chlorinated volatile organic compound polluted regional groundwater samples was investigated. Because of known issues within water remediation using AOP such as toxification by transformation products, this study aimed at complete mineralization of the contained organic micropollutants. Moreover, the influences of variable process parameters such as flow rate, ozone concentration, and radiation dose on process performance were statistically evaluated and discussed. Parameter optimization using a Box-Behnken experimental design resulted in very promising degradation rates. It was thus possible to achieve a degradation rate of at least 98% for cis-dichloroethene, trichloroethene and tetrachloroethene and 85% for trichloromethane without formation of transformation products. The results of this work open up the possibility of developing innovative technologies based on AOP, which can be universally applied even to challenging matrices such as groundwater.

PMID:34920281 | DOI:10.1016/j.jenvman.2021.114236