StaTips Part VI: Bivariate correlation

A very common situation in medical research, including orthodontics, is when a researcher has to verify the association between 2variables, best referred to as bivariate correlation. Bivariate correlation is an analysis that measures the strength of relationship between twovariables through the calculation of different correlation coefficients. The most common correlation coefficients are: Pearson (r), Kendall(rho), Spearman (rho) and the point-biserial (rpb). The choice of the correct coefficient is based on the type of data to be analysed and, forsome of them, the existence of assumptions for using parametrical tests. Indications on how to choose the correct coefficient and abouttheir interpretation are provided

StaTips Part IV: Selection, interpretation and reporting of the intraclass correlation coefficient

The intraclass correlation coefficient (ICC) is an index or repeatability that reflects both the degree of correlation and agreement between measurements. The ICC is widely used in orthodontic research for any continuous data set that satisfies assumptions for using the parametric methods. However, the ICC comprises a total of ten different variants not always recognized by researchers, which may give different outcomes. Here, a practical guide to choose the corrected variant of the ICC based on study design, and three different aspects (referred to as ‘model’, ‘type’ and ‘definition’) is provided. Finally, a full example of correct data interpretation and reporting is included

StaTips Part I: Choosing statistical test when dealing with differences

When dealing with statistical test hypothesis, one of the most common problems to deal with relates to the difference between or among groups, treatments or time points. Herein, a short guide is provided to chose the proper statistical test according to the nature of the data and study design

Regulation of cytotoxic lymphocyte effector functions

Studies of patients with inborn errors of immunity provide an important opportunity to understand the human immune system in a natural context. The articles in this thesis are a compilation of such investigations. With our work, we aimed to identify the cause of primary hemophagocytic lymphohistiocytosis (HLH) in an unexplained pediatric patient (paper I), explore the modulation of SAMD9 and SAMD9L gain-of-function (GOF) mutants (paper II), and understand natural killer (NK) cell biology in the context of DEF6 deficiency (paper III). In paper I, we uncovered biallelic loss-of-function variants in RHOG in a 4-monthold patient presenting with HLH and displaying defective lymphocyte exocytosis. Deletion of RHOG in a human NK cell line abrogated exocytosis that could be rescued by constructs expressing wild type RHOG protein. Moreover, we found that MUNC13-4, associated with autosomal recessive familial HLH type 3, required RHOG interactions for recruitment to the plasma membrane during cytotoxic granule exocytosis. Thus, we demonstrated that RHOG is essential in cytotoxic granule exocytosis by human T and NK cells and proposed that biallelic loss-offunction mutations in RHOG are a novel cause for familial HLH. In paper II, we examined a variety of pathogenic SAMD9 and SAMD9L GOF variants associated with syndromes encompassing bone marrow failure, autoinflammation or selective loss of NK cells, B cells, and monocytes. We sought to understand whether viral host range factors, which are known to antagonize wild-type SAMD9 and SAMD9L proteins, could counteract the anti-proliferative and anti-translational activities of these pathogenic variants. SAMD9 or SAMD9L variants and viral factors were overexpressed in a cell line, followed by biochemical and functional analyses. Vaccinia virus K1 exhibited the highest inhibitory capacity but could not antagonize a truncated variant of SAMD9L that lacked the K1 binding site. The other factors (M062, C7 and KI) could interact with all the SAMD9 and SAMD9L mutants but displayed low capacity in antagonizing the anti-translational and anti-proliferative action of SAMD9/9L mutants. This study provided some novel insights into the structure and the regulation of SAMD9/9L proteins. Additionally, it showed that targeting pathogenic GOF SAMD9/L mutants via viral host range factors or, more broadly speaking, by protein-protein interaction is possible. Autosomal recessive mutations in DEF6 are associated with autoimmunity and severe herpes virus infections. While the latter is a hallmark of NK cell deficiencies, this cell type has not been thoroughly studied in DEF6-deficient patients. In paper III, we surveyed the role of DEF6 in NK cell development and function. We analyzed NK cell phenotypes in DEF6-deficient patients from two unrelated families and found a reduction in canonical CD56dimPLZF+ NK cells concomitant with the expansion of CMV-induced adaptive CD56dimPLZF– NK cells. Deletion of DEF6 in induced pluripotent stem cells gave rise to mature NK cells in an in vitro culture system. In primary human NK cells, deletion of DEF6 reduced cell viability, degranulation and IFN-γ production. We therefore postulate that impaired canonical NK cell survival and function may contribute to the viral susceptibility of DEF6 deficient individuals. To conclude, these studies have shed light on several cellular and molecular mechanisms behind IEI. These mechanisms enlarge our understanding of cytotoxic lymphocytes and of the immune system in general. Moreover, they have inspired us to pursue new directions and experimental approaches in our research

StaTips Part VIII: Confidence interval for the sample mean

When conducting research on a given type of patients, it is impossible to examine all the existing subjects of that type (population) to derive the true mean of the parameter of interest. More realistically, by the investigation of a small group of subjects (sample) from the whole population, researchers can estimate an interval into which the true mean of the population lies. In statistics, such interval is referred to as confidence interval (CI). The calculation of the CI from a sample mean is simple and gives important information, not only regarding the true mean of the population, but also on the statistical significance of the difference between groups being compared. For these reasons, the reporting of the CIs is preferred over the p value alone

StaTips Part II: Assessment of the repeatability of measurements for continuous data

Primary research requests the recording of data through measurements, such as linear and angular parameters in cephalometric, strength of adhesion, skeletal maturation stages and so on. In all of these cases, an analysis of the method error, i.e. repeatability of the measurements, is a fundamental part of the study. In this paper, the case of the continuous data set will be taken into consideration

Hiperparatiroidismo primario, secundario y terciario : actualización

Fil: Perinetti, H. A.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Medicina Quirúrgic

Gingival crevicular fluid alkaline phosphatase activity as a non-invasive biomarker of skeletal maturation

To cite this article: Perinetti G, Baccetti T, Contardo L, Di Lenarda R: Gingival crevicular fluid alkaline phosphatase activity as a non-invasive biomarker of skeletal maturation Orthod Craniofac Res 2011; 14 :44–50Perinetti G, Baccetti T, Contardo L, Di Lenarda RTo evaluate the gingival crevicular fluid (GCF) alkaline phosphatase (ALP) activity in growing subjects in relation to the stages of individual skeletal maturation.The Department of Biomedicine, University of Trieste. Seventy-two healthy growing subjects (45 women and 27 men; range, 7.8–17.7 years).Double-blind, prospective, cross-sectional design. Samples of GCF were collected from each subject at the mesial and distal sites of both of the central incisors, in the maxilla and mandible. Skeletal maturation phase was assessed through the cervical vertebral maturation (CVM) method. Enzymatic activity was determined spectrophotometrically.The relationship between GCF ALP activity and CVM stages was significant. In particular, a twofold peak in enzyme activity was seen at the CS3 and CS4 pubertal stages, compared to the pre-pubertal stages (CS1 and CS2) and post-pubertal stages (CS5 and CS6), at both the maxillary and mandibular sites. No differences were seen between the maxillary and mandibular sites, or between the sexes.As an adjunct to standard methods based upon radiographic parameters, the GCF ALP may be a candidate as a non-invasive clinical biomarker for the identification of the pubertal growth spurt in periodontally healthy subjects scheduled for orthodontic treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79300/1/j.1601-6343.2010.01506.x.pd

Gingival crevicular fluid alkaline phosphatase activity in relation to pubertal growth spurt and dental maturation: A multiple regression study

Introduction: The identification of the onset of the pubertal growth spurt has major clinical implications when dealing with orthodontic treatment in growing subjects. Aim: Through multivariate methods, this study evaluated possible relationships between the gingival crevicular fluid (GCF) alkaline phosphatase (ALP) activity and pubertal growth spurt and dentition phase. Materials and methods: One hundred healthy growing subjects (62 females, 38 males; mean age, 11.5±2.4 years) were enrolled into this doubleblind, prospective, cross-sectional-design study. Phases of skeletal maturation (pre - pubertal, pubertal, post - pubertal) was assessed using the cervical vertebral maturation method. Samples of GCF for the ALP activity determination were collected at the mesial and distal sites of the mandibular central incisors. The phases of the dentition were recorded as intermediate mixed, late mixed, or permanent. A multinomial multiple logistic regression model was used to assess relationships of the enzymatic activity to growth phases and dentition phases. Results: The GCF ALP activity was greater in the pubertal growth phase as compared to the pre - pubertal and post - pubertal growth phases. Significant adjusted odds ratios for the GCF ALP activity for the pre - pubertal and post - pubertal subjects, in relation to the pubertal group, were 0.76 and 0.84, respectively. No significant correlations were seen for the dentition phase. Conclusions: The GCF ALP activity is a valid candidate as a non - invasive biomarker for the identification of the pubertal growth spurt irrespective of the dentition phase