Multivariate Permutation Tests Research Articles

Performance on clinical outcomes, activities of daily living anduser experience on head-mounted displays for people withvision impairment.

To compare the objective performance, acceptance and usability of head-mounted displays (HMDs) to provide evidence-based data that could be used to increase the efficiency of device referrals based upon a person's vision loss and functional needs. A cross-sectional, counterbalanced, individually controlled crossover study was performed on 15 adults with various eye conditions. Performance was measured when using four HMDs: eSight4, Eyedaptic EYE3, Eyedaptic EYE4 and IrisVision Inspire. Performance on clinical visual acuity tests and contrast were assessed, as well as vision-related activities of daily living (ADL) which were divided into three categories: Reading, Searching & Identifying and Eye-hand Coordination. User-experience was also assessed. Logistic regression analyses, Friedman one-way repeated measure analyses of variance by ranks and multivariate permutation testing were used for analysis. There was a significant improvement in visual acuity when using all devices. For contrast tasks, only the eSight4 and Eyedaptic EYE3 improved performance relative to baseline. For most Reading and Searching & Identifying tasks, the odds of being able to perform the tasks were significantly higher while using the devices. However, the actual performance with most devices (e.g., number of words read or reading speed) did not improve significantly over baseline for most tasks. For the Eye-hand Coordination tasks, participants performed equivalent to or significantly poorer than baseline when using the devices. No demographic or clinical predictors of outcomes were identified. Participants expressed dissatisfaction with the devices' effectiveness, acceptability and usability. While performance on clinical tests was better when using the devices, performance on most real-world ADLs was equal to or worse than baseline. No single device improved performance on all tasks, and performance on any one task was not improved with all the devices. The overall dissatisfaction with the devices paralleled the lack of objective improvement in the performance of real-world tasks.

Microhabitat characterization in the home range of the Mule deer (Odocoileus hemionus) in arid zones

Knowing the home range of a species helps to identify the resources it needs to survive and reproduce and how this behavior is expressed spatially. Within home ranges, core areas are the sites where the main resources are abundant. The microhabitat is a spatial area composed of variables that can affect individual behavior. In this sense, the characterization of this inner part of the home range can contribute significantly to understanding the elements that these areas offer compared to the rest of the habitat of a population. This work characterized the home range and areas outside it, as well as the core areas of female mule deer on a microhabitat scale in the Chihuahuan Desert, México. The structure and composition of the vegetation were characterized according to three habitat use hierarchies: interior of the core areas and zones within and outside the home ranges of seven female mule deer. A Principal Component Analysis (PCA) was performed, and a hierarchical clustering was used to relate the variables. The variation in structure and composition in each hierarchy was evaluated by performing multivariate permutation tests. Twenty-five plant species were recorded in the transects. The PCA showed the most similar use hierarchies are the core and home range inner areas. The core area presents higher density and cover-dominance values, and the zone outside the home range showed high values of distance to the individual closest to the central point and greater variation in this parameter. The MANOVA indicated a significant variation in vegetation structure and composition in relation to use hierarchies. Significant differences in vegetation structure and composition were found at the microhabitat level between the core area of activity and the zones within and outside the home range. The core area has a greater structural complexity of vegetation, with greater plant coverage-abundance and density; this suggests that the core area is located in a more competitive and saturated environment. Outside the home range, the microhabitat has greater spatial heterogeneity of vegetation, with greater distance and variation of plant cover. Future research could address the spatial (micro-macro) and temporal scales to better understand the ecological dynamics of the species in different habitat use hierarchies.

Habitat structure shapes temperate reef assemblages across regional environmental gradients

Intertidal artificial habitats are proliferating, but are generally simpler in structure and host lower biodiversity than natural rocky reefs. Eco-engineering aims to enhance the biodiversity of coastal infrastructure, often through physical structural modifications that mimic topographic properties of natural shores. Relationships between biotic assemblages and structural properties of natural and artificial reefs have been extensively studied at sampling scales of up to 1 m2. But evidence that quantified local structural variation has an appreciable influence on biotic assemblages, at a shore-wide scale across regional environmental gradients, is lacking. Here we addressed this knowledge gap with an observational study at 32 natural and artificial intertidal reef sites in Wales, UK. We used multivariate community analysis and permutation tests to examine associations between local physical structure, regional environmental variables and sessile biotic assemblages. A potential influence of local habitat structure on assemblage composition was evident across regional-scale environmental gradients. Compared to natural sites, artificial reefs had lower taxonomic richness, distinct and more variable assemblage composition, and different physical structure. After removing the effect of habitat (natural or artificial), canonical correspondence analysis showed that environmental variables (wave exposure, sea surface temperature and salinity variation), along with two metrics of physical structure (standard deviation in log-transformed detrended roughness and skewness of surface verticality, both at 0.5 m scale), explained 40 % of the variation in assemblage composition among sites. The two structural metrics independently explained 14.5 % of the variation. Associations identified between individual taxa and environmental variables indicated that sites with a higher proportion of horizontal surfaces hosted more canopy macroalgae, which in turn support other algae and invertebrates. Our findings provide evidence to inform scaling-up of structural eco-engineering interventions from experimental contexts to enhance the biodiversity of coastal infrastructure across regional extents.

Testing exchangeability of multivariate distributions

Although there have been a number of available tests of bivariate exchangeability, i.e. bivariate symmetry for bivariate distributions, the literature is void of tests whether a multivariate distribution with more than two dimensions is exchangeable or not. In this paper, multivariate permutation tests of exchangeability of multivariate distributions are proposed, which are based on the non-parametric combination methodology, i.e. on combining non-parametric bivariate exchangeability tests. Numerical experiments on real as well as simulated multivariate data with more than two dimensions are presented here. The multivariate permutation test turns out to be typically more powerful than a bivariate exchangeability test performed only over a single pair of variables, and also more suitable compared to tests exploiting the approaches of Benjamini–Yekutieli or Bonferroni.

Burnout Toll on Empathy Would Mediate the Missing Professional Support in the COVID-19 Outbreak.

PurposeThe year 2020 was marked by the COVID-19 pandemic, massively disruptive at the general population level and for healthcare systems. We aimed to evaluate the psychological distress associated with work-related experiences among medical professionals and supporting staff during the pandemic outbreak.Patients and MethodsA cross-sectional survey was conducted between April and May 2020, employing a self-administered on-line questionnaire that included the collection of socio-demographic and professional status information, Hamilton Anxiety Rating Scale, nine-item Patient Health Questionnaire (PHQ-9), Maslach Burnout Inventory - General Survey, Connor-Davidson Resilience Scale, and a subscale of the International Personality Item Pool (IPIP) for empathy. A total of 364 professionals of the county-coordinated area responded. Descriptive statistics summarized the findings and a mediation model was analyzed, applying the causal step strategy. The specific direct and causal mediation effects were estimated with the bias-corrected and accelerated bootstrap sampling method.ResultsAnxiety, burnout, stress, resilience, and empathy proved to be significantly associated with both the professional category (ie, consultant, specialty doctor, trainee doctor, senior nurse, trainee nurse or other) and the perceived professional support (the nonparametric multivariate permutation test resulted in p=0.048 and p<0.001, respectively). When controlling for the marital and professional status, the female gender had an OR=2.26, 95% CI (1.21; 4.22) toward a high level of empathy compared to males. The causal mediation effect of the perceived lack of professional support on empathy through burnout-depersonalization was highly significant (p<0.001) with an average of 0.0599, 95% CI (0.0238; 0.10), while the direct effect was non-significant (p=0.536) with an average of 0.0295, 95% CI (−0.0774; 0.15).ConclusionWe highlighted the impact of the lack of professional support on healthcare workers’ empathy through burnout-depersonalization in a context of a high workload, time pressure, job stress beyond previous training, and inherently limited organizational support, which are potentially modifiable factors in the mid-term.

Arithmetic processing in children with dyscalculia: an event-related potential study.

IntroductionDyscalculia is a specific learning disorder affecting the ability to learn certain math processes, such as arithmetic data recovery. The group of children with dyscalculia is very heterogeneous, in part due to variability in their working memory (WM) deficits. To assess the brain response to arithmetic data recovery, we applied an arithmetic verification task during an event-related potential (ERP) recording. Two effects have been reported: the N400 effect (higher negative amplitude for incongruent than for congruent condition), associated with arithmetic incongruency and caused by the arithmetic priming effect, and the LPC effect (higher positive amplitude for the incongruent compared to the congruent condition), associated with a reevaluation process and modulated by the plausibility of the presented condition. This study aimed to (a) compare arithmetic processing between children with dyscalculia and children with good academic performance (GAP) using ERPs during an addition verification task and (b) explore, among children with dyscalculia, the relationship between WM and ERP effects.Materials and MethodsEEGs of 22 children with dyscalculia (DYS group) and 22 children with GAP (GAP group) were recorded during the performance of an addition verification task. ERPs synchronized with the probe stimulus were computed separately for the congruent and incongruent probes, and included only epochs with correct answers. Mixed 2-way ANOVAs for response times and correct answers were conducted. Comparisons between groups and correlation analyses using ERP amplitude data were carried out through multivariate nonparametric permutation tests.ResultsThe GAP group obtained more correct answers than the DYS group. An arithmetic N400 effect was observed in the GAP group but not in the DYS group. Both groups displayed an LPC effect. The larger the LPC amplitude was, the higher the WM index. Two subgroups were found within the DYS group: one with an average WM index and the other with a lower than average WM index. These subgroups displayed different ERPs patterns.DiscussionThe results indicated that the group of children with dyscalculia was very heterogeneous and therefore failed to show a robust LPC effect. Some of these children had WM deficits. When WM deficits were considered together with dyscalculia, an atypical ERP pattern that reflected their processing difficulties emerged. Their lack of the arithmetic N400 effect suggested that the processing in this step was not useful enough to produce an answer; thus, it was necessary to reevaluate the arithmetic-calculation process (LPC) in order to deliver a correct answer.ConclusionGiven that dyscalculia is a very heterogeneous deficit, studies examining dyscalculia should consider exploring deficits in WM because the whole group of children with dyscalculia seems to contain at least two subpopulations that differ in their calculation process.

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma.

Simple SummaryHodgkin lymphoma (HL) is a common type of cancer that is characterized by rare, malignant cells among an inflammatory microenvironment. Specific systemic, inflammatory plasma proteins have demonstrated prognostic significance in adult HL; however, systemic inflammation has not been well-characterized in childhood HL. The aim of our study was to better define the inflammatory pre-therapy plasma proteome and identify plasma proteins associated with clinical features of childhood HL. We measured plasma concentrations of 135 proteins in 56 pediatric subjects with newly diagnosed HL and 47 healthy pediatric controls. We found that the plasma protein profile was distinct from controls, and unique proteins were associated with high-risk disease (IL-10, TNF-α, IFN-γ, IL-8), slow early therapy response (CCL13, IFN-λ1, IL-8), and relapse (TNFSF10). These proteins could be used to improve risk stratification, and thus optimize outcomes and minimize unnecessary toxic exposures for those with childhood HL.Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed–Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL. Pre-therapy plasma samples were obtained from pediatric subjects with newly diagnosed HL and healthy pediatric controls. Plasma concentrations of 135 cytokines/chemokines were measured with the Luminex platform. Associations between protein concentration and disease characteristics were determined using multivariate permutation tests with false discovery control. Fifty-six subjects with HL (mean age: 13 years, range 3–18) and 47 controls were analyzed. The cytokine/chemokine profiles of subjects with HL were distinct from controls, and unique cytokines/chemokines were associated with high-risk disease (IL-10, TNF-α, IFN-γ, IL-8) and slow early response (CCL13, IFN-λ1, IL-8). TNFSF10 was significantly elevated among those who ultimately relapsed and was significantly associated with worse event-free survival. These biomarkers could be incorporated into biologically based risk stratification to optimize outcomes and minimize toxicities in pediatric HL.

Accuracy of Edentulous Computer-Aided Implant Surgery as Compared to Virtual Planning: A Retrospective Multicenter Study.

Purpose: To evaluate the accuracy of computer-aided dental implant positions obtained with mucosal-supported templates as compared to Three-Dimensional (3D) planning. Materials and methods: One-hundred implants were inserted into 14 edentulous patients using the All-on-4/6 protocol after surgical virtual planning with RealGUIDE, 3DIEMME, and Geomagic software. After 6 months, three-dimensional neck (V) and apex (S) spatial coordinates of implants and angle inclination displacements as compared to virtual plans were evaluated. Results: The S maxilla coordinates revealed a significant discrepancy between clinical and virtual implant positions (p-value = 0.091). The V coordinates showed no significant differences (p-value = 0.71). The S (p-value = 0.017) and V (p-value = 0.038) mandible coordinates showed significant discrepancies between the clinical and virtual positions of the screws. Implant evaluation showed a 1-mm in average of the horizontal deviation in the V point and a 1.6-mm deviation in the S point. A mean 5° angular global deviation was detected. The multivariate permutation test of the S (p-value = 0.02) confirmed the difference. Greater errors in the mandible were detected as compared to the maxilla, and a higher S discrepancy was found in the posterior jaw compared to the anterior section of both the mandible and maxilla. Conclusions: Computer-aided surgery with mucosal-supported templates is a predictable procedure for implant placement. Data showed a discrepancy between the actual dental implant position as compared to the virtual plan, but this was not statistically significant. However, the horizontal and angle deviations detected indicated that flap surgery should be used to prevent implant positioning errors due to poor sensitivity and accuracy in cases of severe jaw atrophy.

Comprehensive Cell Specific Transcriptome Profiling of a Pediatric Hodgkin Lymphoma Cohort

Introduction: Pathogenic Hodgkin Reed-Sternberg (HRS) cells constitute approximately 1% of Hodgkin lymphoma (HL) tumor cells. Studies characterizing genomic lesions and gene expression of HRS gene cells have been limited due to technical challenges of studying these rare cells, and the majority of existing data has focused on adult HL. We therefore developed a multi-parameter flow sorting strategy to isolate viable cells from pediatric HL tumors and to define the transcriptomes of HRS cells and infiltrating lymphocytes in order to inform underlying mechanisms of HL pathogenesis and also create an opportunity to identify cell-specific biomarkers to predict disease risk and response to therapy. Methods : Flow cytometry was used to sort HRS cells, CD4+ T cells, CD8+ T cells, and CD20+/30+B cells from pediatric subjects' HL lesions and control tonsils. Purity was confirmed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Affymetrix GeneChip HTA 2.0 was used to assess the gene expression profiles (GEPs) for 16 HRS primary tumor cell samples, 14 HL CD4+ and CD8+ T cell samples, 6 control tonsillar CD20+, CD30+, CD4+, and CD8+ cell samples, and 6 HL cell lines. Unsupervised hierarchical clustering and principal component analysis (PCA) were used to determine relatedness, and Cibersort was performed to confirm the phenotype of the sorted cell types. GEPs of HRS, HL CD4+, and HL CD8+ cells were compared to respective controls using a univariate t-test. Significance was determined using a multivariate permutation test with the confidence level of FDR assessment at 80 percent and the maximum allowed proportion of false-positive proteins at 0.1. Gene set enrichment analysis (GSEA) and ingenuity pathway analysis (IPA) were performed to analyze DEGs. Results: Effectiveness of the sorting strategy of HRS cells was confirmed by quantitative RT-PCR and IHC that demonstrated significant enrichment of CD30expression and CD30+ cells in the sorted HRS cell fraction. GEP comparisons were performed for 13 HL samples with matched HRS/CD4+/CD8+ cells: HRS vs. control tonsil CD20+/CD30+ (1934 and 3846 DEGs, respectively), HL CD4+ vs. control CD4+ (635 DEGs), HL CD8+ vs. control CD8+ (2 DEGs). We carried out a transcriptomic analysis of HRS cells, and a set of multifunctional genes were more than 2-fold downregulated (P &lt; .001), involved in telomere maintenance and packaging (TERF2, RFC3, DNA2 and a group of HIST1) when compared to healthy lymph node CD30+ cells. A set of genes related to cytokine/chemokine dysregulation was also upregulated in HRS cells, including IL6, CCL18, and CXCL9. IPA and GSEA of specific HRS genes were also performed and demonstrated pathways associated with HL pathogenesis, including NFĸB activation and T cell exhaustion. Over-expression of genes associated with T cell pathways was demonstrated in HRS cells. While this may be a result of T cell rosetting and contamination, it may also reflect innate T cell signature within HRS cells, as HRS cells clustered separately from T cells in both unsupervised hierarchical clustering and PCA. Cibersort analysis of HRS cells revealed a heterogeneous phenotype that may reflect aberrant differentiation. In comparing clinical characteristics within HRS cells, TCEAL1 was elevated in slow vs. rapid early responders and 3 DEGs were identified when comparing EBV+/- samples. Within HL CD8 cells, KLF2 was elevated in EBV- samples. Conclusions: This study was the first to successfully isolate highly purified HRS cell populations from whole HL lesions in a pediatric HL cohort. Transcriptomic analysis of pediatric HRS cells identified mechanisms previously associated with HL pathogenesis, and also identified potential novel mechanisms, including telomere maintenance. Additional analyses demonstrated significant heterogeneity of HRS trasncriptomes across specimens that may reflect distinct differentiation pathways and differences in HRS-immune cell interactions. Finally, this study identified increased expression of some genes associated with EBV status and response to therapy. Future studies in an expanded cohort will validate these findings, compare pediatric and adult GEPs, and test these cell-specific biomarkers into the current risk stratification strategies of prospective clinical trials. Disclosures No relevant conflicts of interest to declare.

Lipidomic Profiling of Plasma Samples in Patients with Newly Diagnosed Multiple Myeloma; A Biomarker Study for Predicting the Response and Toxicities of Melphalan, Prednisolone and Bortezomib (MPB) Regimen : An Ancillary Study of the JCOG1105 (JCOG1105A1)

Lipidomic Profiling of Plasma Samples in Patients with Newly Diagnosed Multiple Myeloma; A Biomarker Study for Predicting the Response and Toxicities of Melphalan, Prednisolone and Bortezomib (MPB) Regimen : An Ancillary Study of the JCOG1105 (JCOG1105A1)

Multivariate permutation tests for two sample testing in presence of nondetects with application to microarray data.

Very often, data collected in medical research are characterized by censored observations and/or data with mass on the value zero. This happens for example when some measurements fall below the detection limits of the specific instrument used. This type of left censored observations is called "nondetects". Such a situation of an excessive number of zeros in a data set is also referred to as zero-inflated data. In the present work, we aim at comparing different multivariate permutation procedures in two-sample testing for data with nondetects. The effect of censoring is investigated with regard to the different values that may be attributed to nondetected values, both under the null hypothesis and under alternative. We motivate the problem using data from allergy research.

Statistical nonparametric mapping: Multivariate permutation tests for location, correlation, and regression problems in neuroimaging

Nonparametric statistical inference via permutation testing is on the rise in neuroimaging research. This rise in popularity is likely in response to recent studies that have demonstrated limitations of parametric inference in certain situations. Nonparametric tests have the appeal of requiring fewer assumptions than their parametric counterparts, and are often touted as being more flexible and more useful for small samples. Furthermore, recent studies have demonstrated the robustness of nonparametric methods in situations when parametric inference fails. As a result, many nonstatistical neuroimaging researchers are likely to believe that nonparametric permutation tests are always a “safe choice” because the results do not depend on distributional assumptions and/or large sample approximations. Alas, this commonly held belief is not entirely accurate, given that nonparametric tests still do rely on assumptions and/or approximations for valid statistical inference. When these assumptions are met, nonparametric permutation tests have the potential to produce valid inferential results for the intended hypotheses. However, as I demonstrate, when these assumptions are violated, nonparametric permutation tests can produce invalid and/or misleading results, which have important implications for the use of such methods in neuroimaging research. All hope is not lost though, as recent theoretical developments in nonparametric statistics can improve current implementations of permutation tests in neuroimaging research.This article is categorized under: Statistical and Graphical Methods of Data Analysis &gt; Nonparametric Methods Statistical and Graphical Methods of Data Analysis &gt; Bootstrap and Resampling Data: Types and Structure &gt; Image and Spatial Data

The Impact of a Shared Decision-Making Training Program on Dementia Care Planning in Long-Term Care.

Shared decision-making (SDM) can be a way for staff to adopt international recommendations advocating the involvement of nursing home residents and their family members in care planning and the development of personalized care plans. The main aim was to analyze the effects of training nursing home staff in the implementation of SDM on agreement of residents' 'life-and-care plans' with the recommendations (primary outcome) and on family caregivers' quality of life and sense of competence, and staff's job satisfaction (secondary outcomes). In the intervention condition, staff attended a training program on the use of SDM with residents and family caregivers in the care planning process. In the control condition, care planning as usual took place. For the primary outcome, in-depth qualitative and quantitative analyses of the care plans were performed. Multivariate Permutation Tests were applied to assess the impact on secondary outcomes. Forty-nine residents and family caregivers and 34 professionals were involved. Overall, many of the care plans developed during the intervention showed a high level of agreement with the care planning recommendations. Both Italian and Dutch care plans showed improvement in the number of clear problem statements (p < 0.001). In Italy, significant improvements (p < 0.05) were also found regarding specific care objectives, documentation of objectives met, and of residents and families' involvement. No impact was found on secondary outcomes. The involvement of residents and family caregivers in care planning contributed to an improvement of the residents' care plans, but it did not have an effect on family caregivers and staff outcomes.

F168. An EEG fingerprint of early protein-energy malnutrition

Early childhood Protein Energy Malnutrition (PEM) is an increasing worldwide phenomenon with lifelong neurodevelopmental consequences. There is thus a need for inexpensive imaging technologies to objectively identify and follow up the neural impact of malnutrition—Electroencephalography being an obvious choice. But EEG studies of PEM are scarce, performed on subjects with multiple stressors, only in the acute phase. A unique opportunity to improve these enquiries is the still ongoing Barbados Nutrition Study (BNS) which enrolled (1967–72) children with PEM during their first year of life. Under the direction of Frank Ramsey and E. Roy John, 248 digital EEG recordings were obtained (children 5–11 years) at the time that the Brain Research Lab and the Cuban Neuroscience Centre were developing quantitative EEG (qEEG; John et al., 1977). Recently, a large subsample of these digital EEGs was recovered. A unique opportunity to identify a qEEG fingerprint of early PEM has thus arisen, and which we here report. The final sample comprised 46 PEM and 62 control recordings (1 min resting state, eyes-closed,19 electrodes 10/20 system, sampling 100 Hz). Qualitative EEG was evaluated using a Likert-type scale. Multivariate Item Response Theory identified a neurophysiological state (NS) as a single latent variable explaining 0.88 of sample variance. qEEG evaluation at the electrodes (topography) consisted in calculating the log-power spectrum both at the scalp electrodes and sources and computing the z transform with regard to the Cuban normative database. Quantitative tomographic EEG (qEEGt) was carried out with CNEURO’s VARETA source analysis procedure based upon an MNI probabilistic template—necessary since MRIs where not available at that time. Multivariate permutation tests (N = 1000) were applied to t-tests in order to assess differences between groups. Qualitative analysis revealed highly significant changes in the latent variable (NS) with the PEM group showing excessive slow-wave, paroxysmal and focal abnormality activity, with a statistically significant effect for groups (p < 0.00001). qEEG (topographic) revealed (PEM) an increment of slow activities (<5 Hz) in centro-parietal electrodes and a decrease of alpha in fronto-central electrodes around 8.98 Hz as well as a significant increase of fast activity >15.2 Hz. qEEGT analysis: the PEM group, showed a significant increment in source power at lower frequencies (<5 Hz) and a decrease of power in alpha (8.9 Hz) in frontal region. The consistent differences in qEEG and qEEGt values between PEM and controls suggest they may be affordable biomarkers for the long-term actual brain impact of early childhood PEM. Excess slow-waves activity and decreased alpha activity in PEM children, may be a qEEG fingerprint of early PEM predicting which is correlated with many types of neuropathology, learning and performance difficulties.

Functional traits reveal environmental constraints on amphibian community assembly in a subtropical dry forest

AbstractThe relationships between functional traits and environmental gradients are useful to identify different community assembly processes. In this work, we used an approach based on functional traits to analyse if changes in hydroperiod and tree covers of ponds are relevant for local amphibian community assembly processes. Ephemeral ponds with low vegetation cover are expected to impose constraints on different species with particular trait combinations and, therefore, to exhibit communities with lower functional diversity than more stable ponds with greater tree cover. Sampling was conducted in 39 temporary ponds located along vegetation and hydroperiod gradients in the most arid portion of the Chaco ecoregion. Seven functional traits were measured in each species present in the regional pool. Associations between these traits and environmental gradients were detected using multivariate ordination techniques and permutation test (RLQand fourth‐corner analyses respectively). Functional diversity indices were then calculated and related to variations in the environmental gradients. The results obtained allowed us to identify different sets of traits associated with hydroperiod and tree cover, suggesting that these environmental variables are relevant for structuring amphibian communities according to interspecific variations in functional traits from both, larval and adult stages. Contrary to our expectations, communities associated with more stable ponds and with greater tree cover exhibited lower functional diversity than expected by chance (and were the ponds with highest species richness). This result indicates that the reduction in relative importance of environmental restrictions imposed by a very short hydroperiod and the lack of tree cover, favours different species of the regional pool that are similar in several functional traits. Accordingly, communities associated with stable ponds with high tree cover exhibited high functional redundancy.

Iron therapy substantially restores qEEG maturational lag among iron-deficient anemic infants

Objective: To use quantitative electroencephalography (qEEG) to assess the impact of iron-deficiency anemia on central nervous system maturation in the first year of life.Method: Twenty-five infants (3–12 months old) presenting ferropenic anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the former, were studied in two stages. Electroencephalogram during spontaneous sleep was recorded from all participants; the fast Fourier transform was calculated to obtain absolute power (AP) and relative power (RP) qEEG measures. In the first stage, a qEEG comparison between CTL1 and IDA was performed. Second stage consisted in comparing qEEG of the IDA infants before and after supplementation with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another control age-matched group (CTL2). Non-parametric multivariate permutation tests (NPT) were applied to assess differences between CTL1 and IDA groups, as well as IDA vs. IDA-IS, and IDA-IS vs. CTL2.Results: More power in slow frequency bands and less power in fast frequency bands in 64% of IDA babies were observed. NPT evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP increased while theta AP and theta and delta RP decreased, reaching almost normal values.Discussion: This work reveals CNS developmental delay through the study of qEEG (less rapid and more slow frequencies) which recovered significantly with iron supplementation. It is concluded that IDA constitutes a high risk factor for a lag of CNS maturation.

Abstract 1467: A large set of miRNAs is deregulated since the earliest steps of human HCC

Abstract Introduction: Hepatocellular carcinoma (HCC) is the result of a stepwise process preceded by the development of premalignant lesions. To assess the involvement of microRNAs (miRNAs) in hepatocarcinogenesis it is critical to understand whether and which miRNAs are involved in the early stages of tumor development. To this end, changes in expression of miRNAs were investigated in low and high grade dysplastic nodules (LGDNs, HGDNs), early HCCs (eHCCs) and progressed HCCs (pHCCs). Materials and Methods: Small RNA sequencing (smallRNA-Seq) was applied to search for liver miRNAs and to profile their expression patterns in 14 cirrhotic nodules (CNs), 9 LGDNs, 6 HGDNs, 6 eHCCs and 20 pHCCs) from 17 patients with liver lesions of different etiology (HCV, HBV and alcohol). To investigate miRNAs differentially expressed in pHCCs towards their matched cirrhotic tissue, we applied the Random-Variance Model (F-test) and Multivariate Permutation Test (Fold Change, FC ≥ 2.0). QRT-PCR analysis was also performed on 14 additional patients with the same etiology of the first cohort for validation of the smallRNA-Seq results. Results: We identified a 62 miRNA expression signature that differentiates pHCCs from matched CNs. Notably, 52/62 miRNAs dysregulated in pHCCs were likewise altered in LGDN and HGDN, suggesting their possible role in HCC onset. Indeed, 28 miRNAs showed lower expression in CN that was significantly increased in LGDNs and remained high up to pHCCs. In contrast, 24 miRNAs displayed an opposite behavior, as their expression was very low or absent all throughout the tumorigenic process, compared to CNs. Interestingly, 2 miRNAs (let-7a-5p, miR-101-3p) showed a progressive decrease, suggesting that they are involved in later stages of the process. To further support the finding that dysregulation of miRNAs is a very early event in HCC development, we performed qRT-PCR in a series of LGDN, HGDN, eHCC and pHCCs from 14 additional patients. We selected for this analysis a handful of miRNAs found dysregulated by NGS analysis. The results demonstrate that all the 6 miRNAs examined (miR-429, miR-141-3p, miR-200a-3p and miR-200b-3p, miR-375 and miR-21-5p), were dysregulated at all stages of the tumorigenic process as compared to CNs. Conclusion: The results demonstrate that miRNAs deregulation may be a critical player in human hepatocarcinogenesis, from early stages to pHCC. They also suggest that some miRNAs might represent biomarkers useful for differential diagnosis of dysplastic and neoplastic liver lesions. Note: This abstract was not presented at the meeting. Citation Format: Francesca Rizzo, Luca Di Tommaso, Pia Sulas, Elena Coviello, Chiara Novello, Alessandro Weisz, Massimo Roncalli, Amedeo Columbano. A large set of miRNAs is deregulated since the earliest steps of human HCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1467. doi:10.1158/1538-7445.AM2017-1467

Focusing on the Chinese health industry: an empirical enquiry on the TCM listed firms. Is large and private beautiful?

TCM is a key part of the Chinese healthcare system and TCM industries might play a growing role in the domestic and international markets. This work focuses on TCM listed companies in China. In particular, we study the effect of ownership and size on corporate performance. Multivariate permutation tests on the effects of ownership and size on corporate performance show that among the TCM listed companies, private companies perform better than state-owned ones, while big companies perform better than small ones. Moreover, the study shows that in TCM industry ownership has stronger effects than size on corporate performance.

Focusing on the Chinese health industry: an empirical enquiry on the TCM listed firms. Is large and private beautiful?

TCM is a key part of the Chinese healthcare system and TCM industries might play a growing role in the domestic and international markets. This work focuses on TCM listed companies in China. In particular, we study the effect of ownership and size on corporate performance. Multivariate permutation tests on the effects of ownership and size on corporate performance show that among the TCM listed companies, private companies perform better than state-owned ones, while big companies perform better than small ones. Moreover, the study shows that in TCM industry ownership has stronger effects than size on corporate performance.

Dependency and truncated forms of combinations in multivariate combination-based permutation tests and ordered categorical variables

ABSTRACTQuite an important problem usually occurs in several multi-dimensional hypotheses testing problems when variables are correlated. In this framework the non-parametric combination (NPC) of a finite number of dependent permutation tests is suitable to cover almost all real situations of practical interest since the dependence relations among partial tests are implicitly captured by the combining procedure itself without the need to specify them [Pesarin F, Salmaso L. Permutation tests for complex data: theory, applications and software. Chichester: Wiley; 2010a]. An open problem related to NPC-based tests is the impact of the dependency structure on combined tests, especially in the presence of categorical variables. This paper’s goal is firstly to investigate the impact of the dependency structure on the possible significance of combined tests in cases of ordered categorical responses using Monte Carlo simulations, then to propose some specific procedures aimed at improving the power of multivariate combination-based permutation tests. The results show that an increasing level of correlation/association among responses negatively affects the power of combination-based multivariate permutation tests. The application of special forms of combination functions based on the truncated product method [Zaykin DV, Zhivotovsky LA, Westfall PH, Weir BS. Truncated product method for combining p-values. Genet Epidemiol. 2002;22:170–185; Dudbridge F, Koeleman BPC. Rank truncated product of p-values, with application to genomewide association scans. Genet Epidemiol. 2003;25:360–366] or on Liptak combination allowed us, using Monte Carlo simulations, to demonstrate the possibility of mitigating the negative effect on power of combination-based multivariate permutation tests produced by an increasing level of correlation/association among responses.