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Statistical Methods for Research Workers

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... For the four enrichment analyses, contingency tables were constructed counting amino acid sites with the different classifications (See Supplementary Methods: OR tests for enrichment for further details) and the OR were calculated using two-tailed and one-tailed Fisher's exact tests [70] for obtaining the corresponding P-values and 95% confidence intervals (CI 95%). It is worth clarifying that when counting residues we did not request exclusivity in the intersections, i.e. a residue with a given CCRpct can intersect with being in DOMAIN, DOSORDER_MOBILE and DNA-RNA_BIND and hence will contribute to the cells in the three corresponding contingency tables. ...
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Constrained Coding Regions (CCRs) in the human genome have been derived from DNA sequencing data of large cohorts of healthy control populations, available in the Genome Aggregation Database (gnomAD) [1]. They identify regions depleted of protein-changing variants and thus identify segments of the genome that have been constrained during human evolution. By mapping these DNA-defined regions from genomic coordinates onto the corresponding protein positions and combining this information with protein annotations, we have explored the distribution of CCRs and compared their co-occurrence with different protein functional features, previously annotated at the amino acid level in public databases. As expected, our results reveal that functional amino acids involved in interactions with DNA/RNA, protein-protein contacts and catalytic sites are the protein features most likely to be highly constrained for variation in the control population. More surprisingly, we also found that linear motifs, linear interacting peptides (LIPs), disorder-order transitions upon binding with other protein partners and liquid-liquid phase separating (LLPS) regions are also strongly associated with high constraint for variability. We also compared intra-species constraints in the human CCRs with inter-species conservation and functional residues to explore how such CCRs may contribute to the analysis of protein variants. As has been previously observed, CCRs are only weakly correlated with conservation, suggesting that intraspecies constraints complement interspecies conservation and can provide more information to interpret variant effects.
... Next, the number of datasets in which a gene is detected as DE would be considered as a gene's vote. The direct data merging approach combines all datasets into one single dataset and uses this dataset corresponding p-values for each input set for a specific pathway, the p-values will be combined using Fisher's [18] or Stouffer's method. ...
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Pathway analysis has been widely used to detect pathways and functions associated with complex disease phenotypes. The proliferation of this approach is due to better interpretability of its results and its higher statistical power compared with the gene-level statistics. A plethora of pathway analysis methods that utilize multi-omics setup, rather than just transcriptomics or proteomics, have recently been developed to discover novel pathways and biomarkers. Since multi-omics gives multiple views into the same problem, different approaches are employed in aggregating these views into a comprehensive biological context. As a result, a variety of novel hypotheses regarding disease ideation and treatment targets can be formulated. In this article, we review 32 such pathway analysis methods developed for multi-omics and multi-cohort data. We discuss their availability and implementation, assumptions, supported omics types and databases, pathway analysis techniques and integration strategies. A comprehensive assessment of each method's practicality, and a thorough discussion of the strengths and drawbacks of each technique will be provided. The main objective of this survey is to provide a thorough examination of existing methods to assist potential users and researchers in selecting suitable tools for their data and analysis purposes, while highlighting outstanding challenges in the field that remain to be addressed for future development.
... The data obtained were subjected to analysis of variance technique [96] for comparing the difference among the elevational ranges with respect to the characteristics under study. A multiple comparison test, i.e., the least significant difference (lsd), was performed for pair wise comparison of elevational ranges. ...
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Juniperus macropoda is the only tree species of a cold desert ecosystem that is experiencing high anthropogenic pressure and has a poor regeneration status due to harsh environmental conditions. Due to the limited distribution of Juniperus macropoda in this region, the species have remained largely unexplored in terms of understanding the distribution pattern along the elevation and soil fertility gradients. Therefore, the current research was carried out along the elevational gradient, starting from the base line at 3000 m above sea level (m asl) asl with an elevational plot distance of 180 m. The study revealed that the average density of J. macropoda declined gradually from the first elevation range, i.e., 3000–3180 m asl onward, and extended up to the elevation range of 3900–4080 m asl. However, the average seedling and sapling densities were highest at mid-elevation and extended up to an elevation range of 4080–4260 m asl. The J. macropoda population formed a reverse J-shaped structure only up to 3540–3720 m asl. The maximum total biomass and carbon density were recorded in the lowest elevational range, and decreased subsequently. The primary soil nutrients under study decreased sharply along the elevational gradient. Seedling, sapling and tree distributions had a significantly positive relationship (p < 0.05) with available N, P, K, SOC, silt and clay contents and were negatively correlated (p < 0.05) with sand contents. The outcome of the study will form the basis for devising a plan for the management and conservation of J. macropoda forests
... For the four enrichment analyses, contingency tables were constructed counting amino acid sites with the different classifications (See Supplementary Methods: OR tests for enrichment for further details) and the OR were calculated using two-tailed and one-tailed Fisher's exact tests [70] for obtaining the corresponding P-values and 95% confidence intervals (CI 95%). It is worth clarifying that when counting residues we did not request exclusivity in the intersections, i.e. a residue with a given CCRpct can intersect with being in DOMAIN, DISORDER_MOBILE and DNA-RNA_BIND and hence will contribute to the cells in the three corresponding contingency tables. ...
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Constrained Coding Regions (CCRs) in the human genome have been derived from DNA sequencing data of large cohorts of healthy control populations, available in the Genome Aggregation Database (gnomAD) [1]. They identify regions depleted of protein-changing variants and thus identify segments of the genome that have been constrained during human evolution. By mapping these DNA-defined regions from genomic coordinates onto the corresponding protein positions and combining this information with protein annotations, we have explored the distribution of CCRs and compared their co-occurrence with different protein functional features, previously annotated at the amino acid level in public databases. As expected, our results reveal that functional amino acids involved in interactions with DNA/RNA, protein-protein contacts and catalytic sites are the protein features most likely to be highly constrained for variation in the control population. More surprisingly, we also found that linear motifs, linear interacting peptides (LIPs), disorder-order transitions upon binding with other protein partners and liquid-liquid phase separating (LLPS) regions are also strongly associated with high constraint for variability. We also compared intra-species constraints in the human CCRs with inter-species conservation and functional residues to explore how such CCRs may contribute to the analysis of protein variants. As has been previously observed, CCRs are only weakly correlated with conservation, suggesting that intraspecies constraints complement interspecies conservation and can provide more information to interpret variant effects.
... P(EG), P(JOH), P(BO) and P(BDM) show the probability values of various individual cointegration tests such as Engle and Granger (1987), Johansen and Juselius (1990), Boswijk (1994) and Bannerjee et al. (1998). We use Fisher's (1971) critical statistic values to determine whether or not cointegration occurs between the variables. Once crucial values provided by Bayer and Hanck (2013) are determined to be less than the computed Fisher (1971) statistics, we can infer in favor of cointegration by rejecting the null hypothesis of no cointegration. ...
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Purpose The main purpose of the present research is to explore the possible effectiveness of information and communication technology (ICT), infrastructure development, exchange rate and governance on inbound tourism demand using time series data in India. Design/methodology/approach The stationarity of the variables is checked by using the ADF, PP and KPSS unit root tests. The paper uses the Bayer-Hanck and auto-regressive distributed lag (ARDL) bounds testing approach to cointegration to examine the existence of long-run relationships; the error-correction mechanism for the short-run dynamics and the vector error correction method (VECM) to test the direction of causality. Findings The findings of the research indicate the presence of cointegration among the variables. Further, long-run results indicate infrastructure development, word-of-mouth and ICT have a positive and significant linkage with international tourist arrivals in India. However, ICT has a positive and significant effect on tourist arrivals in the short run as well. The VECM results indicate long-run unidirectional causality from infrastructure, ICT, governance and exchange rate to tourist arrivals. Research limitations/implications This study implies that inbound tourism demand in India can be augmented by improving infrastructure, governance quality and ICT penetration. For an emerging country like India, this may have far-reaching implications for sustaining and improving tourism sector growth. Originality/value This paper is the first of its kind to empirically examine the impact of ICT, infrastructure and governance quality in India using modern econometric techniques. Inbound tourism demand research aids government and policymakers in developing effective public policies that would reposition India to gain from a highly competitive global tourism industry.
... Rather than simply referring to an individual's total available evidence, allowing for a socially-extended and conventionally-restricted evidence base better characterises inquiry in science and law. 74 J. Neyman and E. S. Pearson were the first to modify Fisher's hypothesis testing to include reference to a class of possible alternative hypotheses (Lehmann, 1993;Fisher, 1925). Mayo's work extends Neyman and Pearson's hypothesis testing by quantifying the extent to which specific alternative hypotheses are severely tested, based on observed data (Neyman & Pearson, 1967). ...
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This essay presents a unified account of safety, sensitivity, and severe testing. S’s belief is safe iff, roughly, S could not easily have falsely believed p, and S’s belief is sensitive iff were p false S would not believe p. These two conditions are typically viewed as rivals but, we argue, they instead play symbiotic roles. Safety and sensitivity are both valuable epistemic conditions, and the relevant alternatives framework provides the scaffolding for their mutually supportive roles. The relevant alternatives condition holds that a belief is warranted only if the evidence rules out relevant error possibilities. The safety condition helps categorise relevant from irrelevant possibilities. The sensitivity condition captures ‘ruling out’. Safety, sensitivity, and the relevant alternatives condition are typically presented as conditions on warranted belief or knowledge. But these properties, once generalised, help characterise other epistemic phenomena, including warranted inference, legal verdicts, scientific claims, reaching conclusions, addressing questions, warranted assertion, and the epistemic force of corroborating evidence. We introduce and explain Mayo’s severe testing account of statistical inference. A hypothesis is severely tested to the extent it passes tests that probably would have found errors, were they present. We argue Mayo’s account is fruitfully understood using the resulting relevant alternatives framework. Recasting Mayo’s condition using the conceptual framework of contemporary epistemology helps forge fruitful connections between two research areas—philosophy of statistics and the analysis of knowledge—not currently in sufficient dialogue. The resulting union benefits both research areas.
... The experiment on insect mortality and enzyme assay was conducted in three replications, and statistical analysis was carried out using a completely randomized design (Fisher and Yates, 1948). The critical differences were determined to distinguish the level of significance at 0.05% among treatments (isolates). ...
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The entomopathogenic Beauveria spp. were acquired from insect cadavers and soil rhizosphere of cotton, groundnut, and castor. Among Beauveria, five spp. derived from infected insects, eight Beauveria found from soil, and one strain of Beauveria bassiana collected from MTCC 9544. Beauveria were characterized for morphology and cuticle-degrading enzyme activity associated with virulence against Bemisia tabaci. The colony morphology, conidial arrangement, size, and shape confirmed all isolates as Beauveria. The chitinase (EC 3.2.1.14) and lipase (EC 3.1.1.3) activities were observed the highest in Beauveria JAU2, while higher protease (EC 3.4.21.4) activity found in JAU4 followed by JAU2 at 240 h. The bio-efficacy of Beauveria (1 × 107 conidia.ml−1) illustrated that potent JAU2 was examined with the highest % mortality and corrected mortality of B. tabaci at 144 h followed by JAU1. The LC90 and LC50were determined from potent (JAU1 and JAU2) and weak (JAU6), and it was found the lowest in JAU2. The most potent Beauveria JAU2, isolated from insect cadaver (Harmivora armigera), was illustrated higher virulence than other isolates. The Beauveria JAU2 were recognized as Beauveria bassiana based on the shape of conidia and size (2.00 to 2.09 µm dia) as examined in SEM. Study insight into recognition of potent Beauveria bassiana JAU2 was linked with cuticle-degrading enzyme activity for insecticidal action. The JAU2 isolate established the most positive correlation (P0.01: 0.864) between chitinase activity and corrected mortality of insect.
... 13 The higher the correlation between these two sets of rankings, the more we are reifying a particular hierarchy of subgroups and entrenching existing disparities in the data. We use Kendall's Tau [78] as a measure of rank correlation, and combine the p-values obtained across runs of random seeds using Fisher's combined probability test [38]. ...
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Research in machine learning fairness has historically considered a single binary demographic attribute; however, the reality is of course far more complicated. In this work, we grapple with questions that arise along three stages of the machine learning pipeline when incorporating intersectionality as multiple demographic attributes: (1) which demographic attributes to include as dataset labels, (2) how to handle the progressively smaller size of subgroups during model training, and (3) how to move beyond existing evaluation metrics when benchmarking model fairness for more subgroups. For each question, we provide thorough empirical evaluation on tabular datasets derived from the US Census, and present constructive recommendations for the machine learning community. First, we advocate for supplementing domain knowledge with empirical validation when choosing which demographic attribute labels to train on, while always evaluating on the full set of demographic attributes. Second, we warn against using data imbalance techniques without considering their normative implications and suggest an alternative using the structure in the data. Third, we introduce new evaluation metrics which are more appropriate for the intersectional setting. Overall, we provide substantive suggestions on three necessary (albeit not sufficient!) considerations when incorporating intersectionality into machine learning.
... continuous vs. categorical). Specifically, we applied Fisher's Exact test [37], a statistical significance test designed for the categorical data type that examines each feature individually and assigns an exact significance value to each feature, on 521,017 categorical genetic features and Welch's t-test [38] on 91 continuous w-score volume features, and for each feature type, we obtained F = 10 independent sets of k = 17 features with the largest effect sizes on the outcome. We used effect size rather than p-value to rank the significance of the features because p-values are affected by sample size and a statistically significant p-value may indicate that a large sample size was used rather than demonstrating an actual significant difference. ...
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Background: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer's type (DAT). Objective: The goal of this study was to develop and analyze novel biomarkers that can help predict the development and progression of DAT. Methods: We used feature selection and ensemble learning classifier to develop an image/genotype-based DAT score that represents a subject's likelihood of developing DAT in the future. Three feature types were used: MRI only, genetic only, and combined multimodal data. We used a novel data stratification method to better represent different stages of DAT. Using a pre-defined 0.5 threshold on DAT scores, we predicted whether a subject would develop DAT in the future. Results: Our results on Alzheimer's Disease Neuroimaging Initiative (ADNI) database showed that dementia scores using genetic data could better predict future DAT progression for currently normal control subjects (Accuracy = 0.857) compared to MRI (Accuracy = 0.143), while MRI can better characterize subjects with stable mild cognitive impairment (Accuracy = 0.614) compared to genetics (Accuracy = 0.356). Combining MRI and genetic data showed improved classification performance in the remaining stratified groups. Conclusion: MRI and genetic data can contribute to DAT prediction in different ways. MRI data reflects anatomical changes in the brain, while genetic data can detect the risk of DAT progression prior to the symptomatic onset. Combining information from multimodal data in the right way can improve prediction performance.
... We then compute the average Euclidean Embeddings' Distance (ED) from the corresponding centroids: 8 ED(l, e) = E n i=0 e i − c i 2 As a sanity check, we apply a significance test to the ED statistic, confirming that representations of same-class examples are close to each other. Specifically, we apply a permutation test (Fisher, 1971), with 1000 repetitions, comparing the class labels to random labels. We find that EDs for both BERT and BERT IT:CLUST are significantly different from random (p < 0.001). ...
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In real-world scenarios, a text classification task often begins with a cold start, when labeled data is scarce. In such cases, the common practice of fine-tuning pre-trained models, such as BERT, for a target classification task, is prone to produce poor performance. We suggest a method to boost the performance of such models by adding an intermediate unsupervised classification task, between the pre-training and fine-tuning phases. As such an intermediate task, we perform clustering and train the pre-trained model on predicting the cluster labels. We test this hypothesis on various data sets, and show that this additional classification phase can significantly improve performance, mainly for topical classification tasks, when the number of labeled instances available for fine-tuning is only a couple of dozen to a few hundred.
... It can reduce the compounded effect on the error rate of the result pairwise test like T-test method. ANOVA was developed by the English statistician Yates and Fisher [76] and has been applied in various fields for data analysis. It has been applied successfully to face recognition and classification [77,78]. ...
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The striking realism of the life-sized ceramic terracotta warriors has been attracting the interest of the public and archaeologists since they were discovered from the mausoleum complex of the first Chinese Emperor Qin Shihuang in the 1970s. It is still debated whether the life-size models were based on individual people or were just crafted from the standardized models. This research examined the facial features of the terracotta warriors in a quantitative and contactless way with the support of the High-precision 3D point cloud modelling technology and the anthropometric method. The similarities and dissimilarities were analyzed among the facial features of terracotta warriors and 29 modern Chinese ethnic groups using mathematical statistics methods such as MDS, ANOVA, ranking analysis and cluster analysis. The results reveal that the features of the terracotta warriors highly resemble those of contemporary Chinese people and indicate that terracotta warriors were crafted from real portraits and intended to constitute a real army to protect the Emperor Qin Shihuang in the afterlife.
... Analysis of the significance of variation in research data assess from various trial effects, and Fisher's test [55] was used for statistical analysis of data. The test of significance was determined by critical differences and was found significant at 5% probability. ...
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Abstract: (1) Background: Arid conditions occur due to climate abnormality in the different biogeog�raphy regions of the world. The aim of this research is to investigate the stoichiometry of manure and moisture regimes on soil properties, microbial biomass C:N:P turnover, and the grain yield of mustard crops under stress in arid conditions; (2) Methods: The field experiment was carried out for 2 years at the farms of the agriculture college of SKN, Jobner (SKRAU Bikaner, Rajasthan). The effects of organic manure, moisture regimes, and saline water treatment on soil properties, such as the soil microbial biomass build-up, loss, turnover, and recycling of carbon (Cmic), nitrogen (Nmic), and phosphorus (Pmic) in the mustard crop were investigated. The twenty-seven treatments studied are described as follows: organic manures (control, FYM @ 10 t ha−1 and vermicompost @ 5 t ha−1 ), moisture regimes (0.4, 0.6, and 0.8 IW/CPE ratio), and saline irrigation water (control, 6, 12 dSm−1 ); (3) Results: Our findings indicate that vermicompost @ 5 t ha−1 significantly increases moisture retention and the available water in soil at 33 kPa and 1500 kPa. The microbial biomass build-up of Cmic increases by 43.13% over the control and 14.36% over the FYM. Similarly, the soil microbial biomass of Nmic, and Pmic also increase considerably. The SHC of the soil is enhanced by the application of farmyard fertilizer and vermicompost. The BD and pH decrease significantly, while the SHC, OC, CEC, and ECe of the soil increase significantly. The build-up, losses, and fluxes of the soil microbial biomass of Cmic, Nmic, and Pmic increase significantly, and the turnover rate decreases under vermicompost @ 5 t ha−1. A significant increase in grain yield was observed. Irrigation with a 0.8 IW/CPE moisture regime significantly decreases the pH of the SHC; (4) Conclusions: We hypothesized the interactive outcomes of the moisture regime and found that organic manure significantly influenced grain and stover yield. The treatments of quality irrigation water and the addition of organic manure are efficient enough to improve soil properties, water holding capacity, and soil microbial biomass C:N:P in stress climatic conditions.
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Dieses Kapitel vermittelt folgende Lernziele: Wissen, was man unter qualitativer Datenanalyse versteht und verschiedene interpretative Auswertungsverfahren kennen. Wissen, was man unter quantitativer Datenanalyse versteht und unterschiedliche statistische Auswertungsansätze voneinander abgrenzen können. Die Logik des klassischen statistischen Signifikanztests zur Überprüfung von Hypothesen erläutern können. Bei quantitativen explorativen (gegenstandserkundenden und theoriebildenden) Studien Methoden der explorativen Datenanalyse beschreiben können. Bei quantitativen deskriptiven (populationsbeschreibenden) Studien die Parameterschätzung mittels Punkt- und Intervallschätzung hinsichtlich unterschiedlicher Arten von Parametern und Stichproben erklären können. Bei quantitativen explanativen (hypothesenprüfenden) Studien die Hypothesenprüfung mittels klassischem statistischem Signifikanztest hinsichtlich verschiedener Arten von Unterschieds-, Zusammenhangs- und Veränderungs-Hypothesen sowie Einzelfall-Hypothesen erläutern können.
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The present study inquires about the dynamicity of the river processes and associated flood vulnerabilities of the Bhagirathi-Hugli River, particularly in the upper catchment area of the river. The geospatial techniques for analyzing the meandering, sinuosity, and other geometric features of the main channel of the Bhagirathi-Hugli River and the morphometric description of the sub-basin accentuate the dynamicity of fluvial processes. The image processing techniques have been employed to measure normalized difference vegetation index (NDVI), modified normalized difference water index (MNDWI), normalized difference built-up index (NDBI), Z-score (standard scores of annual rainfall), and rainfall erosivity index and analyze them as the major factors of flood vulnerability using the geospatial platform. A composite flood vulnerability index has been formulated to identify the potential flood risk zones in the study districts. The rainfall data of 2000 and 2015 of the study area have been collected to analyze the standardized rainfall. The maps of standardized rainfall have been compared with the surface flow raster of the year 2000 and 2015. The factors of terrain and streamflow also have an impact on flood frequency and intensity; those predict the normalized difference flood index by multiple linear regression model. The major consequences of flood hazards of the Bhagirathi-Hugli sub-basin have been identified in the northeastern and southwestern portions of Murshidabad district, northern and mid-portions of Nadia district, and eastern part of Purba Bardhaman district under the Bhagirathi-Hugli sub-basin area. Howsoever, diverse factors and mechanisms in controlling flood have been analyzed aiming to formulate integrated flood management plans. To eradicate the severe flood hazard risks and minimize its vulnerability, integrated flood management program needs to be implemented with community participation, preparedness, resilience, and capacity building in the study area. Keywords: Flood hazard, Fluvial processes, Flood vulnerability, Bhagirathi-Hugli sub-basin, Geospatial techniques
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Social capital has declined in both developments and in other developing economies, while income inequality has tended to increase. Recent studies show the correlation between social capital and income inequalities, while few studies analyse the direction of causality at a macro level. This paper aims to investigate the causal relationship between generalised trust, as well as income inequalities in 23 economies belonging to the Organisation for Economic Cooperation and Development (OECD) from 2000 to 2019. In this study, we use the application of a fully modified least squares model (FMOLS) and the canonical correlation regression estimator (CCR). In addition, the unit root and cointegration test is applied before applying the Granger causality test. The findings show that there is a bidirectional relationship between social capital and income inequality.
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Background Environmental concerns are growing globally. The world has suffered severe environmental deterioration over the years. Undeniably, the impact of environmental degradation on the earth’s geographical space is alarming, making environmental stakeholders to be worried. Existing literature has examined several factors affecting the environment, but the focus has now shifted to education and the need to maximize its potentials. Although studies have examined the direct impacts of education on the environment, those investigating its moderating role are relatively new and scarce, particularly across income groups. Understanding the channel through which education might affect the environment requires the knowledge of its moderating role. Therefore, this study employs FMOLS, DOLS, ARDL-PMG, CCEMG and heterogeneous panel causality test methodologies to investigate the direct and moderating effects of education in the growth-energy-environment linkages in heterogeneous income groups of 92 countries from 1985 to 2018. Results The findings of this study indicate that economic growth is a long-term solution to environmental deterioration in high and upper-middle-income countries, while the opposite holds for lower-middle-income and low-income countries. In addition, energy consumption is linked with environmental degradation across all income groups. Also, the study finds that education’s direct effects aggravate environmental degradation across all income groups. Moreover, its moderating role ameliorates the adverse effects of energy consumption on environmental degradation in high and upper-middle-income groups but worsens it in the lower-middle-income and low-income groups. Conclusion This study examines the role of education in economic growth, energy consumption and environmental degradation nexus. The study concludes that education is important for environmental sustainability as it encourages pro-environmental behaviors and attitudes and supports energy-efficient products and investments in green technologies. However, education may also aid energy-intensive activities and dirty technology by supporting lifestyles that are not eco-friendly. It is important, therefore, to provide education that promotes better environmental quality.
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Background The APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide 3) family of cytidine deaminases is responsible for two mutational signatures (SBS2 and SBS13) found in cancer genomes. APOBEC3 enzymes are activated in response to viral infection, and have been associated with increased mutation burden and TP53 mutation. In addition to this, it has been suggested that APOBEC3 activity may be responsible for mutations that do not fall into the classical APOBEC3 signatures (SBS2 and SBS13), through generation of double strand breaks.Previous work has mainly focused on the effects of APOBEC3 within individual tumour types using exome sequencing data. Here, we use whole genome sequencing data from 2451 primary tumours from 39 different tumour types in the Pan-Cancer Analysis of Whole Genomes (PCAWG) data set to investigate the relationship between APOBEC3 and genomic instability (GI). Results and conclusions We found that the number of classical APOBEC3 signature mutations correlates with increased mutation burden across different tumour types. In addition, the number of APOBEC3 mutations is a significant predictor for six different measures of GI. Two GI measures (INDELs attributed to INDEL signatures ID6 and ID8) strongly suggest the occurrence and error prone repair of double strand breaks, and the relationship between APOBEC3 mutations and GI remains when SNVs attributed to kataegis are excluded.We provide evidence that supports a model of cancer genome evolution in which APOBEC3 acts as a causative factor in the development of diverse and widespread genomic instability through the generation of double strand breaks. This has important implications for treatment approaches for cancers that carry APOBEC3 mutations, and challenges the view that APOBECs only act opportunistically at sites of single stranded DNA.
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We report on the functional connectivity (FC), its intraclass correlation (ICC), and heritability among 70 areas of the human cerebral cortex. FC was estimated as the Pearson correlation between averaged prewhitened Blood Oxygenation Level-Dependent time series of cortical areas in 988 young adult participants in the Human Connectome Project. Pairs of areas were assigned to three groups, namely homotopic (same area in the two hemispheres), ipsilateral (both areas in the same hemisphere), and heterotopic (nonhomotopic areas in different hemispheres). ICC for each pair of areas was computed for six genetic groups, namely monozygotic (MZ) twins, dizygotic (DZ) twins, singleton siblings of MZ twins (MZsb), singleton siblings of DZ twins (DZsb), non-twin siblings (SB), and unrelated individuals (UNR). With respect to FC, we found the following. (a) Homotopic FC was stronger than ipsilateral and heterotopic FC; (b) average FCs of left and right cortical areas were highly and positively correlated; and (c) FC varied in a systematic fashion along the anterior–posterior and inferior-superior dimensions, such that it increased from anterior to posterior and from inferior to superior. With respect to ICC, we found the following. (a) Homotopic ICC was significantly higher than ipsilateral and heterotopic ICC, but the latter two did not differ significantly from each other; (b) ICC was highest for MZ twins; (c) ICC of DZ twins was significantly lower than that of the MZ twins and higher than that of the three sibling groups (MZsb, DZsb, SB); and (d) ICC was close to zero for UNR. Finally, with respect to heritability, it was highest for homotopic areas, followed by ipsilateral, and heterotopic; however, it did not differ statistically significantly from each other.
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As machine learning has gradually entered into ever more sectors of public and private life, there has been a growing demand for algorithmic explainability. How can we make the predictions of complex statistical models more intelligible to end users? A subdiscipline of computer science known as interpretable machine learning (IML) has emerged to address this urgent question. Numerous influential methods have been proposed, from local linear approximations to rule lists and counterfactuals. In this article, I highlight three conceptual challenges that are largely overlooked by authors in this area. I argue that the vast majority of IML algorithms are plagued by (1) ambiguity with respect to their true target; (2) a disregard for error rates and severe testing; and (3) an emphasis on product over process. Each point is developed at length, drawing on relevant debates in epistemology and philosophy of science. Examples and counterexamples from IML are considered, demonstrating how failure to acknowledge these problems can result in counterintuitive and potentially misleading explanations. Without greater care for the conceptual foundations of IML, future work in this area is doomed to repeat the same mistakes.
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We clarify fundamental aspects of end-user elicitation, enabling such studies to be run and analyzed with confidence, correctness, and scientific rigor. To this end, our contributions are multifold. We introduce a formal model of end-user elicitation in HCI and identify three types of agreement analysis: expert , codebook , and computer . We show that agreement is a mathematical tolerance relation generating a tolerance space over the set of elicited proposals. We review current measures of agreement and show that all can be computed from an agreement graph . In response to recent criticisms, we show that chance agreement represents an issue solely for inter-rater reliability studies and not for end-user elicitation, where it is opposed by chance disagreement . We conduct extensive simulations of 16 statistical tests for agreement rates, and report Type I errors and power. Based on our findings, we provide recommendations for practitioners and introduce a five-level hierarchy for elicitation studies.
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Is science in the midst of a crisis of replicability and false discoveries? In a recent article, Alexander Bird offers an explanation for the apparent lack of replicability in the biomedical sciences. Bird argues that the surprise at the failure to replicate biomedical research is a result of the fallacy of neglecting the base rate. The base-rate fallacy arises in situations in which one ignores the base rate—or prior probability—of an event when assessing the probability of this event in the light of some observed evidence. By extension, the replication crisis would result from ignoring the low prior probability of biomedical hypotheses. In this paper, my response to Bird’s claim is twofold. First, I show that the argument according to which the replication crisis is due to the low prior of biomedical hypotheses is incomplete. Second, I claim that a simple base-rate fallacy model does not account for some important methodological insights that have emerged in discussions of the replication crisis.
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Background A new technology for a self-powered acoustic tag (SPT) was developed for active tracking of juvenile fish, intended to avoid the typical battery life constraints associated with active telemetry technology. We performed a laboratory study to evaluate a subdermal tagging technique for the SPT and effects of the tag on survival, tag retention, and growth in juvenile white sturgeon ( Acipenser transmontanus ). Results Survival was associated with tag retention. White sturgeon implanted with the SPT ( n = 30) had 93% survival and tag retention by day 28, 67% by day 101, and 38% by day 595 post-tagging. Sturgeon implanted with a passive integrated transponder (PIT) tag only (control group) had 96% survival and tag retention by day 28, and through day 101 post-tagging. Fish in the PIT group were repurposed after day 101, so no comparisons with this group were made at day 595 post-tagging. Specific growth rate (SGR) for fork length was a median of 0.25% day ⁻¹ by day 28 for the SPT group, which was significantly lower than the PIT group (median: 0.42% day ⁻¹ ; n = 27). The SPT and PIT groups had similar SGR fork length by day 101 post-tagging (0.22 and 0.25% day ⁻¹ , respectively). SGR weight was also lower for the SPT group compared to the PIT group on day 28 (1.39 and 2.11% day ⁻¹ , respectively), but the difference again dissipated by day 101 (0.79 and 0.88% day ⁻¹ , respectively). Conclusion The tagging technique and placement of the SPT allowed the tag to remain upright along the flank of the sturgeon to ensure maximum battery output of the SPT; however, retention rates of the SPT were not ideal. We provided suggestions to improve the tagging technique. Suggestions included tagging fish that are > 400 mm FL, moving the incision location to extend the cavity and create a pocket for the placement of the SPT, and performing a quantitative wound-healing evaluation. Future studies are therefore recommended to evaluate these suggestions.
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