The bounds of meta-analytics and an alternative method.

OBJECTIVES: Meta-analysis is a statistical appraisal of the data analytic implications of published articles (Y), estimating parameters including the odds ratio and relative risk. This information is helpful for evaluating the significance of the findings. The Higgins I2 index is often used to measure heterogeneity among studies. The objectives of this article are to amend the Higgins I2 index score in a novel and innovative way and to make it more useful in practice. METHODS: Heterogeneity among study populations can be affected by many sources, including the sample size and study design. They influence the Cochran Q score and, thus, the Higgins I2 score. In this regard, the I2 score is not an absolute indicator of heterogeneity. Q changes by bound as Y increases unboundedly. An innovative methodology is devised to show the conditional and unconditional probability structures. RESULTS: Various properties are derived, including showing that a zero correlation between Q and Y does not necessarily mean that they are independent. A new alternative statistic, S2, is derived and applied to mild cognitive impairment and coronavirus disease 2019 vaccination for meta-analysis. CONCLUSIONS: A hidden shortcoming of the Higgins I2 index is overcome in this article by amending the Higgins I2 score. The usefulness of the proposed methodology is illustrated using 2 examples. The findings have potential health policy implications.

Regenerative Signatures in Bronchioalveolar Lavage of Acute Respiratory Distress Syndrome.

Background: In patients with severe acute respiratory distress syndrome (ARDS) associated with sepsis, lung recovery is considerably delayed, and mortality is much high. More insight into the process of lung regeneration in ARDS patients is needed. Exosomes are important cargos for intercellular communication by serving as autocrine and/or paracrine. Cutting-edge exomics (exosomal proteomics) makes it possible to study the mechanisms of re-alveolarization in ARDS lungs. Aims: This study aimed to identify potential regenerative niches by characterizing differentially expressed proteins in the exosomes of bronchioalveolar lavage (BAL) in ARDS patients. Methods: We purified exosomes from BAL samples collected from ARDS patients by NIH-supported ALTA and SPIROMICS trials. The abundance of exosomal proteins/peptides was quantified using liquid chromatography-mass spectrometry (LC-MS). Differentially expressed exosomal proteins between healthy controls and ARDS patients were profiled for functional annotations, cell origins, signaling pathways, networks, and clinical correlations. Results: Our results show that more exosomal proteins were identified in the lungs of late-stage ARDS patients. Immune cells and lung epithelial stem cells were major contributors to BAL exosomes in addition to those from other organs. We enriched a wide range of functions, stem cell signals, growth factors, and immune niches in both mild and severe patients. The differentially expressed proteins that we identified were associated with key clinical variables. The severity-associated differences in protein-protein interaction, RNA crosstalk, and epigenetic network were observed between mild and severe groups. Moreover, alveolar type 2 epithelial cells could serve as both exosome donors and recipients via autocrine and paracrine mechanisms. Conclusions: This study identifies novel exosomal proteins associated with diverse functions, signaling pathways, and cell origins in ARDS lavage samples. These differentiated proteins may serve as regenerative niches for re-alveolarization in injured lungs.

The role of histological subtypes in the survival of patients diagnosed with cutaneous or mucosal melanoma in the United States of America.

BACKGROUND: Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. METHODS: A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. RESULTS: The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [95% CI: (7.58, 12.07)]. CONCLUSIONS: Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk.

An Analysis of COVID-19 Mortality During the Dominancy of Alpha, Delta, and Omicron in the USA.

BACKGROUND: The objective of the study was to measure the risk of death due to COVID-19 in relation to individuals' characteristics, and severity of their disease during the dominant periods of Alpha, Delta, and Omicron variants have influenced mortality rates. METHODS: This study was conducted using COVID-19 Centers for Disease Control and Prevention (CDC) Case Surveillance Public Data Taskforce for 57 states, and United States territories between January 1, 2020 and March 20, 2022. Multivariable binary Hyperbolastic regression of type I was used to analyzes the data. RESULTS: Seniors and ICU-admitted patients had the highest risk of death. For each additional percent increase in fully vaccinated individuals, the odds of death deceased by 1%. The odds of death prior to vaccine availability, compared to post vaccine availability, was 1.27. When comparing the time periods each variant was dominant, the odds of death was 3.45-fold higher during Delta compared to Alpha. All predictor variables had P-values ≤.001. CONCLUSION: There was a noticeable difference in the odds of death among subcategories of age, race/ethnicity, sex, PMCs, hospitalization, ICU, vaccine availability, variant, and percent of fully vaccinated individuals.

Trends in Traumatic Brain Injury Among U.S. Service Members Deployed in Iraq and Afghanistan, 2002-2016.

INTRODUCTION: Traumatic brain injury (TBI) is a major health issue for service members deployed and is more common in recent conflicts; however, a thorough understanding of risk factors and trends is not well described. This study aims to characterize the epidemiology of TBI in U.S. service members and the potential impacts of changes in policy, care, equipment, and tactics over the 15 years studied. METHODS: Retrospective analysis of U.S. Department of Defense Trauma Registry data (2002-2016) was performed on service members treated for TBI at Role 3 medical treatment facilities in Iraq and Afghanistan. Risk factors and trends in TBI were examined in 2021 using Joinpoint regression and logistic regression. RESULTS: Nearly one third of 29,735 injured service members (32.4%) reaching Role 3 medical treatment facilities had TBI. The majority sustained mild (75.8%), followed by moderate (11.6%) and severe (10.6%) TBI. TBI proportion was higher in males than in females (32.6% vs 25.3%; p<0.001), in Afghanistan than in Iraq (43.8% vs 25.5%; p<0.001), and in battle than in nonbattle (38.6% vs 21.9%; p<0.001). Patients with moderate or severe TBI were more likely to have polytrauma (p<0.001). TBI proportion increased over time, primarily in mild TBI (p=0.02), slightly in moderate TBI (p=0.04), and most rapidly between 2005 and 2011, with a 2.48% annual increase. CONCLUSIONS: One third of injured service members at Role 3 medical treatment facilities experienced TBI. Findings suggest that additional preventive measures may decrease TBI frequency and severity. Clinical guidelines for field management of mild TBI may reduce the burden on evacuation and hospital systems. Additional capabilities may be needed for military field hospitals.

The Effect of Naloxone Access Laws on Fatal Synthetic Opioid Overdose Fatality Rates.

BACKGROUND: Increases in fatal synthetic opioid overdoses over the past 8 years have left states scrambling for effective means to curtail these deaths. Many states have implemented policies and increased service capacity to address this rise. To better understand the effectiveness of policy level interventions we estimated the impact of the presence of naloxone access laws (NALs) on synthetic opioid fatalities at the state level. METHODS: A multivariable longitudinal linear mixed model with a random intercept was used to determine the relationship between the presence of NALs and synthetic opioid overdose death rates, while controlling for, Good Samaritan laws, opioid prescription rate, and capacity for medication for opioid use disorder (MOUD), utilizing a quadratic time trajectory. Data for the study was collected from the National Vital Statistics System using multiple cause-of-death mortality files linked to drug overdose deaths. RESULTS: The presence of an NAL had a significant (univariate P-value = .013; multivariable p-value = .010) negative relationship to fentanyl overdose death rates. Other significant controlling variables were quadratic time (univariate and multivariable P-value < .001), MOUD (univariate P-value < .001; multivariable P-value = .009), and Good Samaritan Law (univariate P-value = .033; multivariable P-value = .018). CONCLUSION: Naloxone standing orders are strongly related to fatal synthetic opioid overdose reduction. The effect of NALs, MOUD treatment capacity, and Good Samaritan laws all significantly influenced the synthetic opioid overdose death rate. The use of naloxone should be a central part of any state strategy to reduce overdose death rate.

A Novel Rabbit Model of Retained Hemothorax with Pleural Organization.

Retained hemothorax (RH) is a commonly encountered and potentially severe complication of intrapleural bleeding that can organize with lung restriction. Early surgical intervention and intrapleural fibrinolytic therapy have been advocated. However, the lack of a reliable, cost-effective model amenable to interventional testing has hampered our understanding of the role of pharmacological interventions in RH management. Here, we report the development of a new RH model in rabbits. RH was induced by sequential administration of up to three doses of recalcified citrated homologous rabbit donor blood plus thrombin via a chest tube. RH at 4, 7, and 10 days post-induction (RH4, RH7, and RH10, respectively) was characterized by clot retention, intrapleural organization, and increased pleural rind, similar to that of clinical RH. Clinical imaging techniques such as ultrasonography and computed tomography (CT) revealed the dynamic formation and resorption of intrapleural clots over time and the resulting lung restriction. RH7 and RH10 were evaluated in young (3 mo) animals of both sexes. The RH7 recapitulated the most clinically relevant RH attributes; therefore, we used this model further to evaluate the effect of age on RH development. Sanguineous pleural fluids (PFs) in the model were generally small and variably detected among different models. The rabbit model PFs exhibited a proinflammatory response reminiscent of human hemothorax PFs. Overall, RH7 results in the consistent formation of durable intrapleural clots, pleural adhesions, pleural thickening, and lung restriction. Protracted chest tube placement over 7 d was achieved, enabling direct intrapleural access for sampling and treatment. The model, particularly RH7, is amenable to testing new intrapleural pharmacologic interventions, including iterations of currently used empirically dosed agents or new candidates designed to safely and more effectively clear RH.

Modality and terminology changes for behavioral health service delivery during the COVID-19 pandemic: a systematic review.

Introduction: The COVID-19 pandemic prompted healthcare professionals to implement service delivery adaptations to remain in compliance with safety regulations. Though many adaptations in service delivery were reported throughout the literature, a wide variety of terminology and definitions were used. Methods: To address this, we conducted a PRISMA review to identify service delivery adaptations across behavioral healthcare services in the United States from March 2020 to May 2022 and to identify variations in terminology used to describe these adaptations. We identified 445 initial articles for our review across eight databases using predetermined keywords. Using a two-round screening process, authors used a team approach to identify the most appropriate articles for this review. Results: Our results suggested that a total of 14 different terms were used to describe service modality changes, with the most frequent term being telehealth (63%). Each term found in our review and the frequency of use across identified articles is described in detail. Discussion: Implications of this review such as understanding modality changes during the COVID-19 pandemic and beyond are discussed. Our findings illustrate the importance of standardizing terminology to enhance communication and understanding among professionals.

Metabolites enhance innate resistance to human Mycobacterium tuberculosis infection.

To determine the mechanisms that mediate resistance to Mycobacterium tuberculosis (M. tuberculosis) infection in household contacts (HHCs) of patients with tuberculosis (TB), we followed 452 latent TB infection-negative (LTBI-) HHCs for 2 years. Those who remained LTBI- throughout the study were identified as nonconverters. At baseline, nonconverters had a higher percentage of CD14+ and CD3-CD56+CD27+CCR7+ memory-like natural killer (NK) cells. Using a whole-transcriptome and metabolomic approach, we identified deoxycorticosterone acetate as a metabolite with elevated concentrations in the plasma of nonconverters, and further studies showed that this metabolite enhanced glycolytic ATP flux in macrophages and restricted M. tuberculosis growth by enhancing antimicrobial peptide production through the expression of the surface receptor sialic acid binding Ig-like lectin-14. Another metabolite, 4-hydroxypyridine, from the plasma of nonconverters significantly enhanced the expansion of memory-like NK cells. Our findings demonstrate that increased levels of specific metabolites can regulate innate resistance against M. tuberculosis infection in HHCs of patients with TB who never develop LTBI or active TB.

Trends in Traumatic Brain Injury Related to Consumer Products Among U.S. School-aged Children Between 2000 and 2019.

INTRODUCTION: Consumer product‒related traumatic brain injury in children is common, but long-term trends have not been well characterized. Understanding the long-term trends in consumer product‒related traumatic brain injury may inform prevention efforts. The study objective is to examine the trends in consumer product‒related traumatic brain injury in school-aged children. METHODS: Data were extracted from the National Electronic Injury Surveillance System-All Injury Program for initial emergency department visits for consumer product‒related traumatic brain injury (2000-2019) in school-aged children and analyzed in 2021. RESULTS: Approximately 6.2 million children presented to emergency department with consumer product‒related traumatic brain injury during 2000-2019. Consumer product‒related traumatic brain injury increased from 4.5% of overall consumer product‒emergency department visits in 2000 to 12.3% in 2019, and its incidence rate (cases per 100,000 population) was higher in males (681.2; 95% CI=611.2, 751.2) than in females (375.8; 95% CI=324.1, 427.6). The annual percentage change in consumer product‒related traumatic brain injury was 3.6% from 2000 to 2008, 13.3% from 2008 to 2012, and ‒2.0% through 2019. Average annual percentage change was higher in females (5.1%; 95% CI=3.4, 6.8) than in males (2.8%; 95% CI=1.6, 3.9). Consumer product‒related traumatic brain injury increased from 2000 to 2012 in females and then remained stable. In males, annual percentage change increased from 2008 to 2012 and then declined through 2019. CONCLUSIONS: Traumatic brain injury incidence rate in school-aged children increased from 2000 to 2019, peaked in 2012, and then declined in males but not in females. Percentage increases were highest in females. Prevention strategies should continue, with a specific focus on reducing consumer product‒related traumatic brain injury in female children.

Stochasticity among Victims of COVID-19 Pandemic.

This article provides a thorough explanation of methods and theoretical concepts to detect infectivity of COVID-19. The concept of heterogeneity is discussed and its impacts on COVID-19 pandemics are explored. Observable heterogeneity is distinguished from non-observable heterogeneity. The data support the concepts of heterogeneity and the methods to extract and interpret the data evidence for the conclusions in this paper. Heterogeneity among the vulnerable to COVID-19 is a significant factor in the contagion of COVID-19, as demonstrated with incidence rates using data of a Diamond Princess cruise ship. Given the nature of the pandemic, its heterogeneity with different social norms, pre- and post-voyage quick testing procedures ought to become the new standard for cruise ship passengers and crew. With quick testing, identification of those infected and thus, not allowing to embark on a cruise or quarantine those disembarking, and other mitigation strategies, the popular cruise adventure could become norm for safe voyage. The novel method used in this article adds valuable insight in the modeling of disease and specifically, the COVID-19 virus.

Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells.

Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, how these transformed mesothelial cells contribute to lung fibrosis remains unclear. Here, we investigated the mechanism of contractile myofibroblast differentiation of PMCs. Transforming growth factor-ß (TGF-ß) induced marked upregulation of calponin 1 expression, which was correlated with notable cytoskeletal rearrangement in human PMCs (HPMCs) to produce stress fibers. Downregulation of calponin 1 expression reduced stress fiber formation. Interestingly, induced stress fibers predominantly contain α-smooth muscle actin (αSMA) associated with calponin 1 but not ß-actin. Calponin 1-associated stress fibers also contained myosin II and α-actinin. Furthermore, focal adhesions were aligned with the produced stress fibers. These results suggest that calponin 1 facilitates formation of stress fibers that resemble contractile myofibrils. Supporting this notion, TGF-ß significantly increased the contractile activity of HPMCs, an effect that was abolished by downregulation of calponin 1 expression. We infer that differentiation of HPMCs to contractile myofibroblasts facilitates stiffness of scar tissue in pleura to promote pleural fibrosis (PF) and that upregulation of calponin 1 plays a central role in this process.

Gastric Pneumatosis After Accidental Ingestion of Concentrated Hydrogen Peroxide: A Case Report.

INTRODUCTION: Hydrogen peroxide is a common oxidizing agent that if ingested may cause injury to the gastrointestinal tract or embolic events. Although therapy is primarily supportive, gastric perforation is a rare but serious complication of corrosive ingestion that may require surgical treatment. CASE REPORT: We report the case of a 77-year-old male who presented for nausea and vomiting after accidentally ingesting approximately 150 milliliters of 35% hydrogen peroxide. Computed tomography revealed gastric pneumatosis and extensive portal venous air. The patient was admitted for observation with plans for endoscopy; however, due to the limitations of our small community hospital, he was transferred to a tertiary care center due to concern for a potential gastric perforation. CONCLUSION: The presence of portal venous air as a result of peroxide ingestion may be treated conservatively depending on presenting symptoms; however, severe injury such as gastrointestinal perforation may necessitate surgical intervention.

Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk.

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the "0" time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α-dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Predicting COVID-19 cases with unknown homogeneous or heterogeneous resistance to infectivity.

We present a restricted infection rate inverse binomial-based approach to better predict COVID-19 cases after a family gathering. The traditional inverse binomial (IB) model is inappropriate to match the reality of COVID-19, because the collected data contradicts the model's requirement that variance should be larger than the expected value. Our version of an IB model is more appropriate, as it can accommodate all potential data scenarios in which the variance is smaller, equal, or larger than the mean. This is unlike the usual IB, which accommodates only the scenario in which the variance is more than the mean. Therefore, we propose a refined version of an IB model to be able to accommodate all potential data scenarios. The application of the approach is based on a restricted infectivity rate and methodology on COVID-19 data, which exhibit two clusters of infectivity. Cluster 1 has a smaller number of primary cases and exhibits larger variance than the expected cases with a negative correlation of 28%, implying that the number of secondary cases is lesser when the number of primary cases increases and vice versa. The traditional IB model is appropriate for Cluster 1. The probability of contracting COVID-19 is estimated to be 0.13 among the primary, but is 0.75 among the secondary in Cluster 1, with a wider gap. Cluster 2, with a larger number of primary cases, exhibits smaller variance than the expected cases with a correlation of 79%, implying that the number of primary and secondary cases do increase or decrease together. Cluster 2 disqualifies the traditional IB model and requires its refined version. The probability of contracting COVID-19 is estimated to be 0.74 among the primary, but is 0.72 among the secondary in Cluster 2, with a narrower gap. The advantages of the proposed approach include the model's ability to estimate the community's health system memory, as future policies might reduce COVID's spread. In our approach, the current hazard level to be infected with COVID-19 and the odds of not contracting COVID-19 among the primary in comparison to the secondary groups are estimable and interpretable.

Analysis of Nonbattle Deaths Among U.S. Service Members in the Deployed Environment.

OBJECTIVE: Describe etiologies and trends in non-battle deaths (NBD) among deployed U.S. service members to identify areas for prevention. BACKGROUND: Injuries in combat are categorized as battle (result of hostile action) or nonbattle related. Previous work found that one-third of injured US military personnel in Iraq and Afghanistan had nonbattle injuries and emphasized prevention. NBD have not yet been characterized. METHODS: U.S. military casualty data for Iraq and Afghanistan from 2001 to 2014 were obtained from the Defense Casualty Analysis System (DCAS) and the Department of Defense Trauma Registry (DoDTR). Two databases were used because DoDTR does not capture prehospital deaths, while DCAS does not contain clinical details. Nonbattle injuries and NBD were identified, etiologies classified, and NBD trends were assessed using a weighted moving average and time-series analysis with autoregressive integrated moving average. Future NBD rates were forecast. RESULTS: DCAS recorded 59,799 casualties; 21.0% (n = 1431) of all deaths (n = 6745) were NBD. DoDTR recorded 29,958 casualties; 11.5% (n = 206) of all deaths (n = 1788) were NBD. After early fluctuations, NBD rates for both Iraq and Afghanistan stabilized at approximately 21%. Leading causes of NBD were gunshot wounds and vehicle accidents, accounting for 66%. Approximately 25% was self-inflicted. A 24% NBD rate was forecasted from 2015 through 2025. CONCLUSIONS: Approximately 1 in 5 deaths were NBD. The majority were potentially preventable, including a significant proportion of self-inflicted injuries. A single comprehensive data repository would facilitate future mortality monitoring and performance improvement. These data may assist military leaders with implementing targeted safety strategies.

Structural Zero Data of COVID-19 Discovers Exodus Probabilities.

BACKGROUND: Challenges to manage, mitigate, or prevent the COVID-19's pandemics are felt by medical, healthcare professionals and governing agencies. Health researchers conduct survey among the citizens to capture their opinion on COVID-19. In such surveys like in Hanafiah and Wan (2020), structural-zero (different from sampling zero) category occurs as they question about perception, knowledge, and communication regarding COVID-19. MATERIALS: The data were collected in a survey conducted among Malaysians by Hanafiah and Wan regarding COVID-19. The survey focused on people's response about the public communication, knowledge, and perception. METHODS: One of the four question categories in the survey is mutually exclusive with the other three questions. Consequently, there will be no entry in that category. Such group is called structurally zero category in the literature. The literature never probed the migrative split to other categories of the unknown proportion belonging to the structural zero category. In this article, the probability-based new and innovative method configures what proportion in that mutually exclusive category and it is the essence of our method. RESULTS: The mutually exclusive nature of subquestions manufactured structural zero in their data. A careful analysis of the data has created so far unknown probability concepts in the literature, which we named as "Exodus probabilities" in this article. Its discovery and utility are illustrated and elaborated with application in COVID-19. This methodology is also useful in applications in engineering, epidemiology, marketing, communication networking, etc. CONCLUSION: What is quite novel about the discovery of the exodus probability in this article is the evolution of the concepts from the structural-zero category. In such situation, when a category is eliminated, the proportions of the sample might have uncommunicatively transited to other viable categories and our research question is all about configuring their proportions. This is an innovative approach.

An introduction to new robust linear and monotonic correlation coefficients.

BACKGROUND: The most common measure of association between two continuous variables is the Pearson correlation (Maronna et al. in Safari an OMC. Robust statistics, 2019. https://login.proxy.bib.uottawa.ca/login?url=https://learning.oreilly.com/library/view/-/9781119214687/?ar&orpq&email=^u). When outliers are present, Pearson does not accurately measure association and robust measures are needed. This article introduces three new robust measures of correlation: Taba (T), TabWil (TW), and TabWil rank (TWR). The correlation estimators T and TW measure a linear association between two continuous or ordinal variables; whereas TWR measures a monotonic association. The robustness of these proposed measures in comparison with Pearson (P), Spearman (S), Quadrant (Q), Median (M), and Minimum Covariance Determinant (MCD) are examined through simulation. Taba distance is used to analyze genes, and statistical tests were used to identify those genes most significantly associated with Williams Syndrome (WS). RESULTS: Based on the root mean square error (RMSE) and bias, the three proposed correlation measures are highly competitive when compared to classical measures such as P and S as well as robust measures such as Q, M, and MCD. Our findings indicate TBL2 was the most significant gene among patients diagnosed with WS and had the most significant reduction in gene expression level when compared with control (P value = 6.37E-05). CONCLUSIONS: Overall, when the distribution is bivariate Log-Normal or bivariate Weibull, TWR performs best in terms of bias and T performs best with respect to RMSE. Under the Normal distribution, MCD performs well with respect to bias and RMSE; but TW, TWR, T, S, and P correlations were in close proximity. The identification of TBL2 may serve as a diagnostic tool for WS patients. A Taba R package has been developed and is available for use to perform all necessary computations for the proposed methods.