Pairwise Multiple Comparison Procedures Research Articles

The effect of carbodiimide on push-out bond strength of fiber posts and endogenous enzymatic activity

BackgroundTo investigate the effect of 0.3 M 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC) aqueous solution pretreatment on push-out bond strength (PBS) and matrix-metalloproteinases (MMPs) activity within radicular dentin when different post cementation strategies were employed.MethodsOne hundred and twenty monoradicular human teeth were endodontically treated and randomly divided into six groups, depending on the cementation strategy and root dentin pretreatment (n = 20): EAR: cementation with an etch-and-rinse adhesive (LuxaBond Total Etch, DMG) and resin cement (LuxaCore Z Dual, DMG); EAR/EDC: 1 min EDC pretreatment after etching + EAR; SE: cementation with a self-etch primer (Multilink Primer, Ivoclar Vivadent) and corresponding cement (Multilink Automix, Ivoclar Vivadent); SE/EDC: self-etch primer + EDC pretreatment + SE; SA: cementation with a universal self-adhesive cement (RelyX Universal, 3 M); SA/EDC: EDC pretreatment + SA. Slices were submitted to PBS test and interfacial nanoleakage evaluation 24 h after cementation or after thermocycling (40.000 cycles, 5–55 °C). To investigate the effect of EDC on MMPs activity, 4 additional first maxillary premolars per group were processed for in situ zymography analysis. Multivariate ANOVA and post hoc Tukey tests were used to analyze PBS values. The data from in situ zymography were analyzed with Kruskal-Wallis test and Dunn’s pairwise multiple comparison procedures (α = 0.05).ResultsThe variables “EDC pretreatment”, “root region” and “thermocycling” significantly influenced PBS (p < 0.05), while the variable “cementation strategy” had no influence (p > 0.05). Thermocycling significantly reduced PBS in SE and SA groups (p < 0.05). EDC was effective in preserving PBS after artificial aging. EDC pretreatment significantly reduced enzymatic activity at baseline in EAR and SE groups, and in SA group after thermocycling (p < 0.05).ConclusionsThe use of EDC prevents the reduction of bond-strength values after artificial aging and silences endogenous enzymatic activity within radicular dentin when different cementation strategies were employed.

Operator versus material influence on film thickness using adhesive resin cement or pre-heated resin composite.

There is a growing interest in using pre-heated composites instead of dual-cured cements when luting indirect restorations. This study evaluated the film thickness obtained from two pre-heated composites and two resin cements, by two different operators. The influence of the materials and the level of expertise of the operator were analyzed. Forty specimens of human dentin and composite discs were prepared and divided into four groups depending on the luting process. Each group was randomly equally divided to be handled by two operators with different levels of experience. Two of the initial four groups were luted using dual-cured cements and the two remaining groups using light-cured pre-heated composites. Specimen discs were cut after luting, and film thickness was measured using a Digital microscope. Data were analyzed using a 2-way ANOVA with the Holm-Sidak pairwise multiple comparison procedure (p < 0.05). Mean film thickness ranged from 156.16 ± 4.7 to 33.82 ± 0.7μm. Significant differences (p < 0.001) were noticed between expert and novice results with pre-heated composites. Within the limits of this study, using pre-heated composites as a luting cement requires a better level of expertise to achieve a clinically acceptable film thickness. Using pre-heated composites as luting agent for indirect restorations requires an experimented skill level to achieve a clinically recommended film thickness.

Omnibus Tests for Multiple Binomial Proportions via Doubly Sampled Framework with Under-Reported Data

Previously, Rahardja (2020) paper (in the first reference list) developed a (pairwise) multiple comparison procedure (MCP) to determine which (proportions) pairs of Multiple Binomial Proportions (with under-reported data), the significant differences came from. Generally, such an MCP test (developed by Rahardja, 2020) is the second part of a two-stage sequential test. In this paper, we derived two omnibus tests (i.e., the overall equality of multiple proportions test) as the first part of the above two-stage sequential test (with under-reported data), in general. Using two likelihood-based approaches, we acquire two Wald-type (Omnibus) tests to compare Multiple Binomial Proportions (in the presence of under-reported data). Our closed-form algorithm is easy to implement and not computationally burdensome. We applied our algorithm to a vehicle-accident data example.

Comparative evaluation of the force required to fracture coronal segments reattached using different methods.

Anterior teeth are prone to traumatic injuries. Their management is necessary in order to maintain the pulp and esthetics. Various methods have been reported for fragment reattachment of fractured teeth but there is no consensus on which is the best technique. The aim of this study was to compare the force required to fracture reattached fragments using polyethylene fibers in vertical grooves on the external surface of teeth, fiber-reinforced composite post and circumferential chamfer. Forty-eight extracted maxillary central incisors were sectioned using a disk and randomly divided into 4groups (n=12): Group 1: control group, Group 2: reattachment followed by placement of two external vertical grooves on the labial surface and restored with polyethylene fibers and hybrid composite, Group 3: reattachment followed by two external vertical grooves and filled with fiber posts and composite, and Group 4: reattachment followed by circumferential chamfer at the fracture line and restored with composite. The forces required to fracture the reattached fragments were measured using a Universal testing machine. Data were analyzed using the Kruskal-Wallis test. Pairwise multiple comparison procedure was done using the Student-Newman-Keuls Method. The highest values for force required to fracture were observed in the fiber post group and the lowest in the Ribbond group (p<.05). The fiber post group had significantly different results compared to the Ribbond and Chamfer preparation groups (p<.05). However, the difference of rank between the fiber post and control groups was not significantly different (p>.05). The force required to fracture the fiber post group was closest to that of intact teeth followed by the chamfer and Ribbond groups, respectively.

Beyond exposure-response: A tutorial on statistical considerations in dose-ranging studies.

Dose‐ranging studies are a crucial part of the phase II drug development process. They complement the understanding gained from exposure‐response analyses. However, the statistical design issues related to dose‐ranging studies are not always keenly understood and a poorly designed study can be costly for later development. In this tutorial, we review five key statistical principles in designing such a study. We also describe some popular statistical approaches, including pairwise comparison, modeling, and Multiple Comparison Procedure modeling in the context of principles.

Multiple Comparison Procedures for the Differences of Proportion Parameters in Over-Reported Multiple-Sample Binomial Data

In sequential tests, typically a (pairwise) multiple comparison procedure (MCP) is performed after an omnibus test (an overall equality test). In general, when an omnibus test (e.g., overall equality of multiple proportions test) is rejected, then we further conduct a (pairwise) multiple comparisons or MCPs to determine which (e.g., proportions) pairs the significant differences came from. In this article, via likelihood-based approaches, we acquire three confidence intervals (CIs) for comparing each pairwise proportion difference in the presence of over-reported binomial data. Our closed-form algorithm is easy to implement. As a result, for multiple-sample proportions differences, we can easily apply MCP adjustment methods (e.g., Bonferroni, Šidák, and Dunn) to address the multiplicity issue, unlike previous literatures. We illustrate our procedures to a real data example.

C5aR1 regulates migration of suppressive myeloid cells required for costimulatory blockade-induced murine allograft survival.

Costimulatory blockade-induced murine cardiac allograft survival requires intragraft accumulation of CD11b+ Ly6Clo Ly6G- regulatory myeloid cells (Mregs) that expand regulatory T cells (Tregs) and suppress effector T cells (Teffs). We previously showed that C5a receptor (C5aR1) signaling on T cells activates Teffs and inhibits Tregs, but whether and/or how C5aR1 affects Mregs required for transplant survival is unknown. Although BALB/c hearts survived >60days in anti-CD154 (MR1)-treated or cytotoxic T-lymphocyte associated protein 4 (CTLA4)-Ig-treated wild-type (WT) recipients, they were rejected at ~30days in MR1-treated or CTLA4-Ig-treated recipients selectively deficient in C5aR1 restricted to myeloid cells (C5ar1fl/fl xLysM-Cre). This accelerated rejection was associated with ~2-fold more donor-reactive T cells and ~40% less expansion of donor-reactive Tregs. Analysis of graft-infiltrating mononuclear cells on posttransplant day 6 revealed fewer Ly6Clo monocytes in C5ar1fl/fl xLysM-Cre recipients. Expression profiling of intragraft Ly6Clo monocytes showed that C5aR1 deficiency downregulated genes related to migration/locomotion without changes in genes associated with suppressive function. Cotransfer of C5ar1fl/fl and C5ar1fl/fl xLysM-Cre myeloid cells into MR1-treated allograft recipients resulted in less accumulation of C5ar1-/- cells within the allografts, and in vitro assays confirmed that Ly6Chi myeloid cells migrate to C5a/C5aR1-initiated signals. Together, our results newly link myeloid cell-expressed C5aR1 to intragraft accumulation of myeloid cells required for prolongation of heart transplant survival induced by costimulatory blockade.

Evaluation of the Efficacy of Bupivacaine (0.5%) alone or with Clonidine (1μg/kg) Versus Control in a Single Level Paravertebral Blockin Patients Undergoing PCNL Procedure.

Percutaneous Nephrolithotomy (PCNL) is a widely used procedure to remove complex upper tract renal calculi by means of a nephroscope. Although less invasive, PCNL is associated with significant pain owing to soft tissue injury. Most of these patients have mild to moderately compromised renal function. An anaesthesia plan that reduces intraoperative requirement of anaesthetics, analgesics, muscle relaxants and postoperative requirement of systemic analgesics is essential. Paravertebral Block (PVB) in combination with general anaesthesia may be an ideal technique for achieving all the goals. To evaluate the efficacy of Bupivacaine (0.5%) alone or with Clonidine (1ug/kg) versus control in a single level paravertebral block for intra-operative and postoperative analgesia in patients undergoing PCNL procedure. In this prospective, randomized, observer blind study we evaluated the intraoperative as well as postoperative analgesic effects of paravertebrally administered Bupivacaine (0.5%) alone or Bupivacaine±Clonidine (1μg/kg) versus Control (Conventional analgesia with IV Paracetamol). We also evaluated requirement of propofol, haemodynamic parameters, need for rescue analgesics & incidence of adverse effects. Collected data was analysed with SPSS statistical software. One way ANOVA test was applied. All pair wise multiple comparison procedures were analysed by Tukey's Method if equal sample size and by Dunnett's Method if unequal sample size in all groups. It was observed that paravertebral block is an effective method for providing intra and postoperative analgesia for PCNL surgery. It reduced the requirement of intraoperative propofol, maintained stable intra and postoperative haemodynamics without any adverse effects or complications. Addition of Clonidine as an adjuvant to Bupivacaine enhanced the quality of paravertebral block with better haemodynamic stability, greater reduction in the intraoperative propofol requirement and provided significantly longer postoperative analgesia without any incident of bradycardia, hypotension, sedation or respiratory compromise. In conclusion, 0.5% Bupivacaine±1μg/kg Clonidine in a single level paravertebral block is useful, effective and safe for providing intra as well as postoperative analgesia during PCNL surgeries.

Robust pairwise multiple comparisons under short-tailed symmetric distributions

In one-way ANOVA, most of the pairwise multiple comparison procedures depend on normality assumption of errors. In practice, errors have non-normal distributions so frequently. Therefore, it is very important to develop robust estimators of location and the associated variance under non-normality. In this paper, we consider the estimation of one-way ANOVA model parameters to make pairwise multiple comparisons under short-tailed symmetric (STS) distribution. The classical least squares method is neither efficient nor robust and maximum likelihood estimation technique is problematic in this situation. Modified maximum likelihood (MML) estimation technique gives the opportunity to estimate model parameters in closed forms under non-normal distributions. Hence, the use of MML estimators in the test statistic is proposed for pairwise multiple comparisons under STS distribution. The efficiency and power comparisons of the test statistic based on sample mean, trimmed mean, wave and MML estimators are given and the robustness of the test obtained using these estimators under plausible alternatives and inlier model are examined. It is demonstrated that the test statistic based on MML estimators is efficient and robust and the corresponding test is more powerful and having smallest Type I error.

The Ability of Von Willebrand Factor (VWF) to Bind Factor VIII (FVIII) Can Decrease during Pregnancy

Background: The coagulation protein von Willebrand Factor (VWF) and its circulating partner protein, Factor VIII, are known to be elevated in pregnancy. However, the nature of changes in VWF which occur during pregnancy are not well understood. We previously presented results from a study of 46 healthy pregnancies in which we measured VWF antigen (VWF:Ag) and Factor VIII (FVIII determined both by activity and antigen measurements). We found that VWF:Ag and FVIII increased during pregnancy, consistent with less FVIII relative to VWF. We have also observed that VWF multimer size can decrease during pregnancy. We hypothesized that pregnancy can induced molecular changes in VWF, and that such changes could impact the interaction of VWF with its ligands, specifically FVIII.Methods: We adapted a Type 2N von Willebrand Disease (VWD) assay to test the ability of plasma VWF to bind recombinant FVIII. In brief, serial dilutions of plasma VWF were captured using a polyclonal anti-VWF antibody (DAKO), endogenous FVIII was stripped using a CaCl2 wash, recombinant FVIII (Recombinate) was applied, and bound FVIII was detected using an anti-FVIII antibody (Cedarlane). In parallel, a VWF:Ag ELISA was performed using the same anti-VWF capture antibody. The VWF-FVIII binding ratio (VWF-FVIIIb) was then determined by dividing the quantity of rFVIII detected by the amount of VWF:Ag immobilized on the plate. The range, reproducibility, and variance of the assay was first determined in a healthy blood donor repository. We then tested VWF-FVIIIb in healthy pregnancies for which 3rd trimester and non-pregnant baseline samples were available. Additional time points during pregnancy were also studied, when available. VWF-FVIIIb results for each trimester and the non-pregnant baseline were analyzed by one-way ANOVA (All Pairwise Multiple Comparison Procedures, Holm-Sidak method).Results: Forty-six healthy pregnancies with non-pregnant baseline samples were studied. Samples tested were drawn in the first (n=6), second (n=38), and third (n=43) trimesters, at 38 weeks gestational age (n=13), and at a non-pregnant time point (baseline). In non-pregnant samples, the VWF-FVIIIb was close to 1.0 (0.988 +/- 0.084), similar to a normal blood donor repository. We identified a significant decrease in VWF-FVIIIb in the second trimester (0.931 +/- 0.82; p = 0.013), which became more pronounced in the third trimester (0.899 +/- 0.75; p < 0.001) and at 38 weeks gestational age (0.88 +/- 0.072; p < 0.001). The means, quartiles, and standard deviations for each pregnancy time point are shown in Figure 1.Conclusions: These data support the hypothesis that VWF can acquire a decreased ability to interact with FVIII during pregnancy. A decreased capacity to carry FVIII could contribute to the increased VWF:FVIII ratio we and others have observed during pregnancy, although other factors, such as increased VWF production relative to FVIII, could also play a role. This work provides further evidence for a new model of acquired VWF changes in the setting of pregnancy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Resins-based denture soft lining materials modified by chlorhexidine salt incorporation: An in vitro analysis of antifungal activity, drug release and hardness

ObjectivesTo evaluate the in vitro growth inhibition of Candida albicans, the rate of chlorhexidine release and shore A hardness from resins-based denture soft lining materials modified by chlorhexidine diacetate (CDA) or chlorhexidine hydrochloride (CHC) incorporation. MethodsResin discs were prepared from soft denture liners based on poly (methyl methacrylate) (PMMA) or poly (ethyl methacrylate) (PEMA) containing 0.5, 1.0 and 2.0wt.% of CDA or CHC. For antifungal activity resin discs were placed on agar plates inoculated with C. albicans, after 48h at 37°C the diameters of inhibition zones were measured. For the chlorhexidine release, discs were immersed into distilled water at 37°C, and spectral measurements were made after 48h. Shore A hardness was evaluated at the baseline, 2 and 7 days, using 6mm thick rectangular specimens also immersed into distilled water at 37°C. Data were statistically processed by SigmaStat software using ANOVA and all pairwise multiple comparison procedures was done using the Holm–Sidak method, with α=0.05 (p<0.001). ResultsCDA added to PMMA soft liner and PEMA soft liner had a dose-related inhibitory effect on C. albicans and on chlorhexidine release rate (p<0.001). The PMMA and PEMA hardness increased statistically by time but not for the different CDA concentrations. CHC had no inhibitory effect on C. albicans. SignificanceChlorhexidine diacetate released from resins-based soft lining materials can be convenient to reduce the biofilm development on the material surface and treat denture stomatitis, without depending on patient compliance.

Tumor Vascular Interaction in Melanomas and Neurogenesis: A Review

Background: Melanomas arise from multipotent neural crest derivative, the melanocytes. At the tumor-stroma interphase, melanoma cells show organized neural differentiation forming tumor-vascular complexes. The present study explores the sequence of neurogenesis from aurophilic radial glial like cells in relation to angiogenesis, utilizing the tumor-vascular-complex (TVC) as a 3D model. Methods: Serial frozen and paraffin sections stained with HE, reticulin-gold impregnation for aurophilia; dopa oxidase; immunopositivity for: neural differentiation (nestin, Glial Fibrillary Acidic Protein (GFAP), Neural Fibrillary Protein (NFP), synaptophysin); indoleamines: (serotonin and melatonin), catecholamines (dopamine (DA), Noradrenalin (NA), pigment; Dopa Oxidase (DO)); hormones: ((PRL), Prolactin; (HGH), Human Growth Hormone;) and mitosis. The pattern of neural differentiation in tumor-vascular-complexes (TVC) is assessed by positivity in layer1- layer 5 and cell counts in each layer of the perimantle zone (PMZ). Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. [t-test or Mann-Whitney U- test]. Results: A TVC is formed during angiogenic tumor-vascular interaction. Nes +ve angiogenic tubes enter the tumor margins. Periluminar cells show aurophilia, and extend dendritic arbors into the outer layers of the mantle zone. Cells and dendritic processes in layer 1/ layer 2 show Nes, Auro and GFAP positivity. NFP and Syn positivity is seen in layer 4/ layer 5 with a transition zone between layer 2/ layer 3. As two layers accrue, a wave of mitotic activity is seen and cells acquire PRL and HGH and indoleamine positivity. Catecholamine positivity is in layer 4/ layer 5 thus establishing a polarity. Dopamine is positive in layer 3/ layer 4 coinciding with dopa-oxidase which peaks in layer 4 with NA, ACTH positivity in the outer layers is in association with pigmentation in layer 4/ layer 5. Discussion: Thus during tumor-vascular interaction, melanoma cells differentiate into aurophilic radial glial like cells, as during embryonic neurogenesis, Nes, a marker of multi-lineage progenitor cells, identifies them as MASC, which differentiate into neuronal cells. The angiogenic vessel confers polarity and an embryonal microenvironment in the perivascular mantle zone of the TVC, inducing aggressive melanoma cells to function as neuronal stem cells recapitulating neurogenesis of bio-aminergic cells. The cell cycle is orchestrated by the three pituitary hormones, PRL, HGH and ACTH. The expression of PRL and HGH is related to mitotic activity while ACTH and pigment indicate differentiated function.

Exploring the efficacy of cyclic vs static aspiration in a cerebral thrombectomy model: an initial proof of concept study

Background and purposeCurrent technology for endovascular thrombectomy in ischemic stroke utilizes static loading and is successful in approximately 85% of cases. Existing technology uses either static suction (applied via a...

Fracture resistance of endodontically treated teeth restored with glass fiber posts of different lengths

Endodontically treated teeth are known to have reduced structural strength. Glass fiber posts may influence fracture resistance and should be evaluated. The purpose of this study was to evaluate the influence of glass fiber post length on the fracture resistance of endodontically treated teeth. Forty intact human maxillary canines were selected and divided into 4 groups, the control group consisting of teeth restored with a custom gold cast post and core, with a length of two-thirds of the root. Other groups received prefabricated glass fiber posts in different lengths: group 1/3, removal of one-third of the sealing material (5 mm); group 1/2, removal of one-half of the sealing material (7.5 mm); and group 2/3, removal of two-thirds of the sealing material (10 mm). All the posts were cemented with resin cement, and the specimens with glass fiber posts received a composite resin core. All the specimens were restored with a metal crown and submitted to a compressive load until failure occurred. The results were evaluated by 1-way ANOVA, and the all pairwise multiple comparison procedures (Tukey honestly significantly difference test) (α=.05). The ANOVA showed significant differences among the groups (P<.002). The Tukey test showed that the control group presented significantly higher resistance to static load than the other groups (control group, 634.94 N; group 1/3, 200.01 N; group 1/2, 212.17 N; and group 2/3, 236.08 N). Although teeth restored with a cast post and core supported a higher compressive load, all of them fractured in a catastrophic manner. For teeth restored with glass fiber posts, the failure occurred at the junction between the composite resin core and the root. The length of glass fiber posts did not influence fracture load, but cast post and cores that extended two-thirds of the root length had significantly greater fracture resistance than glass fiber posts.

Push-out bond strengths of different dental cements used to cement glass fiber posts

Since the introduction of glass fiber posts, irreversible vertical root fractures have become a rare occurrence; however, adhesive failure has become the primary failure mode. The purpose of this study was to evaluate the push-out bond strength of glass fiber posts cemented with different luting agents on 3 segments of the root. Eighty human maxillary canines with similar root lengths were randomly divided into 8 groups (n=10) according to the cement assessed (Rely X luting, Luting and Lining, Ketac Cem, Rely X ARC, Biscem, Duo-link, Rely X U100, and Variolink II). After standardized post space preparation, the root dentin was pretreated for dual-polymerizing resin cements and untreated for the other cements. The mixed luting cement paste was inserted into post spaces with a spiral file and applied to the post surface that was seated into the canal. After 7 days, the teeth were sectioned perpendicular to their long axis into 1-mm-thick sections. The push-out test was performed at a speed of 0.5 mm/min until extrusion of the post occurred. The results were evaluated by 2-way ANOVA and the all pairwise multiple comparison procedures (Tukey test) (α=.05). ANOVA showed that the type of interaction between cement and root location significantly influenced the push-out strength (P<.05). The highest push-out strength results with root location were obtained with Luting and Lining (S3) (19.5 ±4.9 MPa), Ketac Cem (S2) (18.6 ±5.5 MPa), and Luting and Lining (S1) (18.0 ±7.6 MPa). The lowest mean values were recorded with Variolink II (S1) (4.6 ±4.0 MPa), Variolink II (S2) (1.6 ±1.5 MPa), and Rely X ARC (S3) (0.9 ±1.1 MPa). Self-adhesive cements and glass ionomer cements showed significantly higher values compared to dual-polymerizing resin cements. In all root segments, dual-polymerizing resin cements provided significantly lower bond strength. Significant differences among root segments were found only for Duo-link cement.

Influence of technique and manipulation on self-adhesive resin cements used to cement intraradicular posts

Resin cements are widely used to cement intraradicular posts, but bond strength is significantly influenced by the technique and material used for cementation. The purpose of this study was to evaluate the bond strength of 3 self-adhesive cements used to cement intraradicular glass fiber posts. The cements all required different application and handling techniques. Forty-five human maxillary canines were selected and randomly divided into 3 groups n= 15 by drawing lots: Group BIS - Biscem, Group BRE - Breeze, and Group MAX - Maxcem. Each group was divided into 3 subgroups according to application and handling techniques: Sub-group A - Automix/Point tip applicator, Sub-group L - Handmix/Lentulo, and Sub-group C - Handmix/Centrix. Cementation of the posts was performed according to the manufacturers' instructions. The push-out test was performed with a crosshead speed of 0.5 mm/min, and bond strength was expressed in megapascals. The results were evaluated by 2-way ANOVA and the all pairwise multiple comparison procedures (Tukey test) (α=.05). Breeze cement showed the highest average for the subgroups A, L, and C when compared to the Biscem cement and Maxcem Elite (P<.05). Statistically significant differences among the subgroups were only observed for Biscem. This study shows that application and handling techniques may influence the bond strength of different self-adhesive cements when used for intraradicular post cementation.

Biogenic amines and tumor-vascular interaction in melanomas

Background In nodular melanomas in vertical growth phase, tumor-vascular complexes (TVC), with perivascular mantle zone (PMZ) of 5 to 6 layers (L1-L5) of tumor cells are formed around angiogenic vessels at the tumor-stroma interphase, showing organized neural differentiaton. The present study explores the sequence of biogenic amines positivity in relation to angiogenesis, utilizing the TVC as a 3D model. Methods The sequence of positivity for Nestin (Nes), GFAP, indoleamines: serotonin (SER)/melatonin (MLT), catecholamines: dopamine (DA)/noradrenalin (NA), pigment (Pig); dopa oxidase (DO); and related mitosis in layers of the PMZ (L1-L5) was assessed in 897 developing TVCs using 5 µm serial paraffin and frozen sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures (Tukey Test). Results Nes, GFAP appear in L1/L2, next indoleamines (serotonin/melatonin) in L2/L3 associated with mitosis. DA is positive in L3/L4 coinciding with DO which peaks in L4 with NA, Pig appears in L4/L5. Mitosis in L2/L3 is associated with indoleamine positive cells which remain in L2/L3, with catecholamine positive cells moving into L4/L5 thus establishing a polarity. Conclusion Thus, the angiogenic vessel confers polarity and an embryonal microenvironment in the PMZ, the aggressive melanoma cells functioning as neuronal stem cells to resemble early neurogenesis of bio-aminergic cells.

Pairwise comparisons of means under realistic nonnormality, unequal variances, outliers and equal sample sizes

A Monte Carlo simulation evaluated six pairwise multiple comparison procedures for controlling Type I error rates, any-pair power, and all-pairs power. Realistic conditions of nonnormality were based on a previous survey, and the effects of outliers were investigated. Variance ratios varied from 1:1 to 8:1. Evaluated procedures included Tukey's honestly significant difference (HSD) preceded by an F-test, the Hayter–Fisher, the Games–Howell procedure tested at 0.9α, the Peritz with F-tests, the Peritz with Brown–Forsythe tests, and the Peritz with Alexander–Govern tests. Peritz with Brown–Forsythe procedure shows the greatest robustness in Type I error control. Any-pair power is generally best with the Hayter–Fisher, whereas all-pairs power is best with the Peritz F-test procedure. Even though the Hayter–Fisher shows only slightly lower all-pair power rates than the Peritz, it is still much easier to perform.

Choosing the best pairwise comparisons of means from non-normal populations, with unequal variances, but equal sample sizes

A Monte Carlo simulation evaluated five pairwise multiple comparison procedures for controlling Type I error rates, any-pair power, and all-pairs power. Realistic conditions of non-normality were based on a previous survey. Variance ratios were varied from 1:1 to 64:1. Procedures evaluated included Tukey's honestly significant difference (HSD) preceded by an F test, the Hayter–Fisher, the Games–Howell preceded by an F test, the Pertiz with F tests, and the Peritz with Alexander–Govern tests. Tukey's procedure shows the greatest robustness in Type I error control. Any-pair power is generally best with one of the Peritz procedures. All-pairs power is best with the Pertiz F test procedure. However, Tukey's HSD preceded by the Alexander–Govern F test may provide the best combination for controlling Type I and power rates in a variety of conditions of non-normality and variance heterogeneity.

Patterns of neural differentiation in melanomas

BackgroundMelanomas, highly malignant tumors arise from the melanocytes which originate as multipotent neural crest cells during neural tube genesis. The purpose of this study is to assess the pattern of neural differentiation in relation to angiogenesis in VGP melanomas using the tumor as a three dimensional system.MethodsTumor-vascular complexes [TVC] are formed at the tumor-stroma interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The pattern of neural differentiation is assessed by immunopositivity for HMB45, GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor-vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test].ResultsThe cells abutting on the basement membrane acquire GFAP positivity and extend processes. New layers of tumor cells show a transition between L2 to L3 followed by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the positivity in the outer layers.DiscussionFrom this study it is seen that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells [GFAP+ve] which further differentiate into neuronal positive cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during neurogenesis, to populate the tumor substance.