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In this study, nanofiltration experiments using synthetic solutions containing acetate, butyrate, and lactate are carried out to assess the impact of the feed composition, i.e., feed concentration and feed proportions, on the separation factor of couples of solutes in binary and ternary solutions. In binary solutions, no influence of the solute proportions in the feed was pointed out, whatever the couple of solutes. The separation factor of acetate/butyrate and acetate/lactate was found to decrease with increasing feed concentration, while that of lactate/butyrate remained constant. The separation factors of acetate/lactate and lactate/butyrate were identical in ternary solutions compared to binary ones, showing no impact of the addition of the third solute. In ternary solutions, the presence of lactate decreased the separation factor of acetate/butyrate, but this decrease was not influenced by the proportion of lactate.

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We conducted a longitudinal cohort study of SARS-CoV-2 and influenza rates in childcare centers and schools in Wuxi, China, collecting 1,760 environmental samples and 9,214 throat swabs from 593 students (regardless of symptoms) in weekly collections during February-June 2023. We estimated a cumulative infection rate of 124.8 (74 episodes)/1,000 persons for SARS-CoV-2 and 128.2 (76 episodes)/1,000 persons for influenza. The highest SARS-CoV-2 infection rate was in persons 18 years of age, and for influenza, in children 4 years of age. The asymptomatic proportion of SARS-CoV-2 was 59.6% and 66.7% for influenza; SARS-CoV-2 symptomatic proportion was lower in 16-18-year-olds than in 4-6-year-olds. Only samples from frequently touched surface tested positive for SARS-CoV-2 (4/1,052) and influenza (1/1,052). We found asynchronous circulation patterns of SARS-CoV-2 and influenza, similar to trends in national sentinel surveillance. The results support vaccination among pediatric populations and other interventions, such as environmental disinfection in educational settings.

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The bioreduction characteristics and mechanisms of Cr(VI) onto Bacillus cereus RCr enhanced by ferric citrate were investigated. The optimum conditions were initial pH 9, temperature 40 °C, inoculation amount 4%, and glucose 3 g/L, respectively. The addition of 1.5 g/L ferric citrate increased the average reduction rate from 120.43 to 220.61 mg/(L∙h) compared with the control (without ferric citrate). The binding capacity of Cr(III) on the cell surface increased to 21%, in which the precipitates were mainly CrO(OH), Cr2O3, and FeCr2O4. Cell membrane was the main site of reduction, related important functional groups: - COOH, C-H, - NH2, C = C, and P-O. Fe(III) increased the yield of NADH and cytochrome c by approximately 48.51% and 68.63%, which significantly facilitated the electron generation and electron transfer, thus increasing the amount of electrons in the bioreduction of heavy metals by an average of 110%. Among the electrons obtained by Cr(VI), the proportion of indirect reduction mediated by Fe(III)/Fe(II) shuttle was 62% on average, whereas direct reduction mediated by reductase was 38%. These results may provide insights into the bioreduction process by bacteria enhanced by Fe(III) for detoxification of heavy metals with multiple valences, as an important step towards improving microbial remediation.

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In laboratory medicine, measurement results are often expressed as proportions of concentrations or counts. These proportions have distinct mathematical properties that can lead to unexpected results when conventional parametric statistical methods are naively applied without due consideration in the analysis of method validation experiments, quality assessments, or clinical studies. In particular, data points near 0% or 100% can lead to misleading analytical conclusions. To avoid these problems, the logit transformation-defined as the natural logarithm of the proportion/(1-proportion)-is used. This transformation produces symmetric distributions centered at zero that extend infinitely in both directions without upper or lower bounds. As a result, parametric statistical methods can be used without introducing bias. Furthermore, homogeneity of variances (HoV) is given. The benefits of this technique are illustrated by two applications: (i) flow cytometry measurement results expressed as proportions and (ii) probabilities derived from multivariable models. In the first case, naive analyses within external quality assessment (EQA) evaluations that lead to inconsistent results are effectively corrected. Second, the transformation eliminates bias and variance heterogeneity, allowing for more effective precision estimation. In summary, the logit transformation ensures unbiased results in statistical analyses. Given the resulting homogeneity of variances, common parametric statistical methods can be implemented, potentially increasing the efficiency of the analysis.

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OBJECTIVES: To evaluate the validity of the Golden Proportion, Golden Percentage, and Recurring Esthetic Dental (RED) Proportion among Kenyans of African descent with naturally well-aligned teeth. MATERIALS AND METHODS: Standardized frontal photographic images of the smiles of 175 participants aged 18-35 years were obtained, and Adobe Photoshop was used to analyze and measure the frontal widths of the maxillary central and lateral incisors and canines in triplicate. The average teeth widths were calculated to determine the existence of the Golden Proportion, Golden Percentage, and RED Proportion, and their validity using independent sample t-tests to compare the differences in the mean teeth widths at α < 0.05. RESULTS: The number of male and female participants was 107 (61.1%) and 68 (38.9%), respectively. The Golden Proportion between the maxillary central and lateral incisors was found in 4.0% on the right and 2.8% on the left of all the participants, but between the maxillary lateral incisors and canines was found in only 0.6% on the right of male participants (p < 0.0001). The RED Proportion between the maxillary lateral and central incisors was in the range of 67%-70%, and between the canines and lateral incisors was 82%-84% (p < 0.0001). The proportion of RED was not constant, and gradually increased distally. The Golden Percentage of 15% was observed in the lateral incisors bilaterally; however, in the central incisors and the canines, the Golden Percentage was 22% and 12%, respectively. CONCLUSION: The Golden and RED Proportions were invalid determinants of anterior teeth proportions. The Golden Percentage existed only in the lateral incisors. The Golden Proportion, RED Proportion, and Golden Percentage theories may not be applicable to all populations when designing smiles. Racial and ethnic backgrounds are important considerations to establish objective quantifiable values of anterior tooth proportions that are beneficial for esthetic restorations.

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BACKGROUND: Infantile nephropathic cystinosis (INC) is a rare lysosomal storage disorder, mostly and often firstly affecting the kidneys, together with impaired disharmonious growth and rickets, eventually resulting in progressive chronic kidney disease (CKD). With the introduction of cysteamine therapy, most pediatric patients reach adulthood with no need for kidney replacement therapy. Still, detailed changes in INC patients' clinical and morphological presentation over the past decades have not yet been thoroughly investigated. METHODS: Two groups with a respective total of 64 children with INC and 302 children with CKD, both treated conservatively and aged 2 to 18 years, were prospectively observed in the time span from 1998 to 2022 with 1186 combined annual clinical and morphological examinations clustered into two measurement periods (1998 to 2015 and ≥ 2016). RESULTS: In INC patients, thoracic proportion indices remained markedly increased, whereas body fat stores remained decreased over the past 25 years (+ 1 vs. below ± 0 z-score, respectively). Their CKD peers presented with overall improved growth, general harmonization of body proportions, and improved body fat stores, while INC patients only presented with an isolated significant increase in leg length over time (∆0.36 z-score). eGFR adjusted for age did not significantly change over the past 25 years in both groups. Alkaline phosphatase (ALP) showed a significant decrease in CKD patients over time, while remaining above normal levels in INC patients. CONCLUSIONS: Disproportionate thoracic shape and impaired body fat stores remain the most characteristic morphological traits in INC patients over the past 25 years, while causal mechanisms remain unclear.

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OBJECTIVE: To address the relationship between the proportions of carbohydrates and fat and hyperglycaemia in the Chinese population. DESIGN: A cross-section research involving data from the China Health and Nutrition Survey in 2009, and nutritional status and health indicators were mainly focused. SETTING: China. PARTICIPANTS: 8197 Chinese individuals aged over 16 years, including 1345 subjects who had a low-carbohydrate and high-fat diet, 3951 individuals who had a medium proportion of carbohydrate and fat diet, 2660 participants who had a high-carbohydrate and low-fat diet and 241 people who had a very-high-carbohydrate and low-fat diet. RESULTS: Subjects with the high-carbohydrate and low-fat diet were significantly associated with an increased risk of hyperglycaemia (OR: 1·142; 95 % CI: 1·022, 1·276) when compared with the individuals with the medium proportion of carbohydrate and fat diet. Meanwhile, people with a very-high-carbohydrate and low-fat diet had a higher risk of hyperglycaemia (OR: 1·829; 95 % CI: 1·377, 2·429). In contrast, the association between participants with a low-carbohydrate and high-fat diet and hyperglycaemia was NS (OR: 1·082; 95 % CI: 0·942, 1·243) with adjusting a series of confounding factors. Furthermore, people with a very-high-carbohydrate and low-fat diet were significantly associated with a higher risk of hyperglycaemia in the major energy levels and social characteristics subgroup. CONCLUSIONS: We found the high-carbohydrate and low-fat and very-high-carbohydrate and low-fat diets were significantly associated with a high risk of hyperglycaemia. And, the association between low-carbohydrate and high-fat diets and the risk of hyperglycaemia was NS.

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BACKGROUND: Positive and negative likelihood ratios (PLR and NLR) are important metrics of accuracy for diagnostic devices with a binary output. However, the properties of Bayesian and frequentist interval estimators of PLR/NLR have not been extensively studied and compared. In this study, we explore the potential use of the Bayesian method for interval estimation of PLR/NLR, and, more broadly, for interval estimation of the ratio of two independent proportions. METHODS: We develop a Bayesian-based approach for interval estimation of PLR/NLR for use as a part of a diagnostic device performance evaluation. Our approach is applicable to a broader setting for interval estimation of any ratio of two independent proportions. We compare score and Bayesian interval estimators for the ratio of two proportions in terms of the coverage probability (CP) and expected interval width (EW) via extensive experiments and applications to two case studies. A supplementary experiment was also conducted to assess the performance of the proposed exact Bayesian method under different priors. RESULTS: Our experimental results show that the overall mean CP for Bayesian interval estimation is consistent with that for the score method (0.950 vs. 0.952), and the overall mean EW for Bayesian is shorter than that for score method (15.929 vs. 19.724). Application to two case studies showed that the intervals estimated using the Bayesian and frequentist approaches are very similar. DISCUSSION: Our numerical results indicate that the proposed Bayesian approach has a comparable CP performance with the score method while yielding higher precision (i.e. a shorter EW).

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BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.

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OBJECTIVES: This study presents biological affinities between the last hunter-fisher-gatherers and first food-producing societies from the Nile Valley. We investigate odontometric and dental tissue proportion changes between these populations from the Middle Nile Valley and acknowledge the biological processes behind them. MATERIALS AND METHODS: Dental remains of 329 individuals from Nubia and Central Sudan that date from the Late Pleistocene to the mid-Holocene are studied. Using 3D imaging techniques, we investigated outer and inner metric aspects of upper central incisors, and first and second upper molars. RESULTS: Late Paleolithic and Mesolithic foragers display homogeneous crown dimensions, dental tissue proportions, and enamel thickness distribution. This contrasts with Neolithic trends for significant differences from earlier samples on inner and outer aspects. Finally, within the Neolithic sample differences are found between Nubian and Central Sudanese sites. DISCUSSION: Substantial dental variation appears to have occurred around 6000 bce in the Nile Valley, coinciding with the emergence of food-producing societies in the region. Archeological and biological records suggest little differences in dietary habits and dental health during this transition. Furthermore, the substantial variations identified here would have happened in an extremely short time, a few centuries at most. This does not support in situ diet-related adaptation. Rather, we suggest these data are consistent with some level of population discontinuity between the Mesolithic and Neolithic samples considered here. Complex settlement processes could also explain the differences between Nubia and Central Sudan, and with previous results based on nonmetric traits.

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We introduce a new class of zero-or-one inflated power logit (IPL) regression models, which serve as a versatile tool for analyzing bounded continuous data with observations at a boundary. These models are applied to explore the effects of climate changes on the distribution of tropical tuna within the North Atlantic Ocean. Our findings suggest that our modeling approach is adequate and capable of handling the outliers in the data. It exhibited superior performance compared to rival models in both diagnostic analysis and regarding the inference robustness. We offer a user-friendly method for fitting IPL regression models in practical applications.

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[This corrects the article DOI: 10.3389/fpubh.2022.969777.].

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Difference in proportions is frequently used to measure treatment effect for binary outcomes in randomized clinical trials. The estimation of difference in proportions can be assisted by adjusting for prognostic baseline covariates to enhance precision and bolster statistical power. Standardization or g-computation is a widely used method for covariate adjustment in estimating unconditional difference in proportions, because of its robustness to model misspecification. Various inference methods have been proposed to quantify the uncertainty and confidence intervals based on large-sample theories. However, their performances under small sample sizes and model misspecification have not been comprehensively evaluated. We propose an alternative approach to estimate the unconditional variance of the standardization estimator based on the robust sandwich estimator to further enhance the finite sample performance. Extensive simulations are provided to demonstrate the performances of the proposed method, spanning a wide range of sample sizes, randomization ratios, and model specification. We apply the proposed method in a real data example to illustrate the practical utility.

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PURPOSE: The inclusion of people with mental disorders (MD) into competitive employment has become an important political and therapeutic goal. The present paper investigates meta-analytically to which extent people with MD who were unemployed or on sick leave due to MD prefer to work in a competitive job environment. METHODS: For this systematic review and meta-analysis of proportions, we searched Medline, PsycInfo, Cinahl, Google Scholar, and reference lists for peer-reviewed publications from 1990 to Dec 2023, which provided data on the job preferences of people with MD. Two authors independently conducted full-text screening and quality assessments. Pooled proportions of job preferences were calculated with a random-effects meta-analysis of single proportions, and subgroup analyses were performed to examine characteristics associated with job preferences. RESULTS: We included 30 studies with a total of 11,029 participants in the meta-analysis. The overall proportion of participants who expressed a preference for competitive employment was 0.61 (95%-CI: 0.53-0.68; I2 = 99%). The subgroup analyses showed different preference proportions between world regions where the studies were conducted (p < 0.01), publication years (p = 0.03), and support settings (p = 0.03). CONCLUSION: Most people with MD want to work competitively. More efforts should be given to preventive approaches such as support for job retention. Interventions should be initiated at the beginning of the psychiatric treatment when the motivation to work is still high, and barriers are lower. TRAIL REGISTRATION: The protocol is published in the Open Science registry at https://osf.io/7dj9r.

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BACKGROUND: Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD. METHODS: Forty-six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre-type distribution and cross-sectional area via immunofluorescence microscopy and RNA-sequenced to generate transcriptome-wide gene expression data. Sex-stratified k-means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co-expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype. RESULTS: Abnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6-min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s-to-forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty-nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co-expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co-expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density. CONCLUSIONS: Our findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co-expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

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BACKGROUND: Early diagnosing Chronic Obstructive Pulmonary Disease (COPD) is relatively difficult. Therefore, the concepts of preserved ratio impaired spirometry (PRISm) and small airway disease (SAD) were proposed to achieve early diagnosis for COPD. Besides, the occurrence of COPD is positively related to age. However, the relationship among COPD, PRISm, and SAD still requires clarification. Thus, we estimated the proportions and risk factors of COPD and PRISm in the positive screening participants, and searched the methods of early diagnosing COPD via the SAD indicators. METHODS: A total of 53,641 residents aged more than 60 years old from Shaoxing City, Zhejiang Province, China, completed a series of screening projects. And 2327 of positive screening participants ultimately finished bronchodilator tests. The data were statistically analyzed to figure out the proportions and risk factors of COPD and PRISm, and the efficacy of early diagnosing COPD by the SAD indicators. RESULTS: Totally 2229 positive screening participants were included, the proportion of PRISm was 6.3% (141/2229), and of COPD was 78.2% (1743/2229). Statistical analyses showed that COPD patients were more likely to be smokers, males, and older. And COPD patients had higher questionnaire scores, meaning that they were more prone to have family history of respiratory diseases and more severe respiratory symptoms. Additionally, COPD patients had lower maximal mid-expiratory flow (MMEF) pred, forced expiratory flow (FEF) 75pred, and FEF50pred. And we found that male sex and presence of respiratory symptoms might lead to COPD and PRISm. Also, the methods of early diagnosing COPD through the SAD indicators might be acceptable. CONCLUSION: There is a close association between COPD and decreased small airway function (SAF) among the participants included. Age, smoking, male sex, worse SAF, and respiratory symptoms might cause the progressing from normal people to PRISm, then to COPD patients. Besides, the SAD indicators such as MMEFpred, FEF75pred, and FEF50pred were included in lung function tests and bronchodilator tests. Intriguingly, it was found that early diagnosing COPD via the SAD indicators might be feasible. In the future, early diagnosis for COPD requires further research.

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Background: Persons with specific phobias typically generalize the dangerousness of the phobic animal to all members of its species, possibly as a result of malfunctioning brain circuitry normally providing quick and dirty identification of evolutionary-relevant stimuli. An objective assessment of which perceptual features make an animal more or less scary to phobic and non-phobic people would help overcome the limitations of the few studies available so far, based on self-reports. Objective: To achieve this aim, we built an augmented reality setting where volunteers with different levels of fear of spiders were asked to make holographic spiders that look either dangerous or harmless. To reach this goal, a computerized interface allowed participants to modify the spider's perceptual features (hairiness, body/leg size, and locomotion) in real time. Results: On average, the dangerous spiders were made hairy, thick, and moving according to spider-like locomotion; coherently, the harmless spiders were made hairless, slim, and moving according to a butterfly-like locomotion. However, these averaged preferences could not fully describe the complex relationship between perceptual preferences with each other and with arachnophobia symptoms. An example of a key finding revealed by cluster analysis is the similarity in perceptual preferences among participants with little or no fear of spiders, whereas participants with more arachnophobia symptoms expressed more varying preferences. Conclusion: Perceptual preferences toward the spider's features were behaviorally assessed through an observational study, objectively confirming a generalization effect characterizing spider-fearful participants. These results advance our knowledge of phobic preferences and could be used to improve the acceptability of exposure therapies.

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OBJECTIVES: Interpretations of the primate and human fossil record often rely on the estimation of somatic dimensions from bony measures. Both somatic and skeletal variation have been used to assess how primates respond to environmental change. However, it is unclear how well skeletal variation matches and predicts soft tissue. Here, we empirically test the relationship between tissues by comparing somatic and skeletal measures using paired measures of pre- and post-mortem rhesus macaques from Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: Somatic measurements were matched with skeletal dimensions from 105 rhesus macaque individuals to investigate paired signals of variation (i.e., coefficients of variation, sexual dimorphism) and bivariate codependence (reduced major axis regression) in measures of: (1) limb length; (2) joint breadth; and (3) limb circumference. Predictive models for the estimation of soft tissue dimensions from skeletons were built from Ordinary Least Squares regressions. RESULTS: Somatic and skeletal measurements showed statistically equivalent coefficients of variation and sexual dimorphism as well as high epiphyses-present ordinary least square (OLS) correlations in limb lengths (R2 >0.78, 0.82), joint breadths (R2 >0.74, 0.83) and, to a lesser extent, limb circumference (R2 >0.53, 0.68). CONCLUSION: Skeletal measurements are good substitutions for somatic values based on population signals of variation. OLS regressions indicate that skeletal correlates are highly predictive of somatic dimensions. The protocols and regression equations established here provide a basis for reliable reconstruction of somatic dimension from catarrhine fossils and validate our ability to compare or combine results of studies based on population data of either hard or soft tissue proxies.

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The weighted sum of binomial proportions and the interaction effect are two important cases of the linear combination of binomial proportions. Existing confidence intervals for these two parameters are approximate. We apply the h-function method to a given approximate interval and obtain an exact interval. The process is repeated multiple times until the final-improved interval (exact) cannot be shortened. In particular, for the weighted sum of two proportions, we derive two final-improved intervals based on the (approximate) adjusted score and fiducial intervals. After comparing several currently used intervals, we recommend these two final-improved intervals for practice. For the weighted sum of three proportions and the interaction effect, the final-improved interval based on the adjusted score interval should be used. Three real datasets are used to detail how the approximate intervals are improved.

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In multicellular organisms, cell types must be produced and maintained in appropriate proportions. One way this is achieved is through committed progenitor cells or extrinsic interactions that produce specific patterns of descendant cell types on lineage trees. However, cell fate commitment is probabilistic in most contexts, making it difficult to infer these dynamics and understand how they establish overall cell type proportions. Here, we introduce Lineage Motif Analysis (LMA), a method that recursively identifies statistically overrepresented patterns of cell fates on lineage trees as potential signatures of committed progenitor states or extrinsic interactions. Applying LMA to published datasets reveals spatial and temporal organization of cell fate commitment in zebrafish and rat retina and early mouse embryonic development. Comparative analysis of vertebrate species suggests that lineage motifs facilitate adaptive evolutionary variation of retinal cell type proportions. LMA thus provides insight into complex developmental processes by decomposing them into simpler underlying modules.

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