Novel statistical approaches for censored immunological data

For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects.I aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, I assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confoundin

Novel statistical approaches for censored immunological data

For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects.I aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, I assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confoundin

Do subjects with acute/subacute temporomandibular disorder have associated cervical impairments: A cross-sectional study

Background There is preliminary evidence of cervical musculoskeletal impairment in some temporomandibular disorder (TMD) pain states. Objectives To determine whether people with TMD, classified as either mild or moderate/severe TMD, have more cervical signs of dysfunction than healthy subjects. Design Cross-sectional survey. Method Based on the Conti Amnestic Questionnaire and examination of the temporomandibular joint (Axis I classification of the Research Diagnostic Criteria for TMD), of 144 people examined 59 were classified to a mild TMD group, 40 to a moderate/severe TMD group and 45 to an asymptomatic control group without TMD. Subjects were evaluated for signs of cervical musculoskeletal impairment and disability including the Neck Disability Index, active cervical range of motion, the Flexion-Rotation Test, mechanical pain threshold of the upper trapezius and obliquus capitis inferior muscles, Cranio-Cervical Flexion test and passive accessory movements of the upper 3 cervical vertebrae. Results According to cervical musculoskeletal dysfunction, the control group without TMD were consistently the least impaired and the group with moderate/severe TMD were the most impaired. These results suggest, that the more dysfunction and pain is identified in the temporomandibular region, the greater levels of dysfunction is observable on a number of cervical musculoskeletal function tests. The pattern of cervical musculoskeletal dysfunction is distinct to other cervical referred pain phenomenon such as cervicogenic headache. Conclusion These findings provide evidence that TMD in an acute/subacute pain state is strongly related with certain cervical spine musculoskeletal impairments which suggests the cervical spine should be examined in patients with TMD as a potential contributing factor

The potential relevance of altered muscle activity and fatigue in the development of performance-related musculoskeletal injuries in high string musicians

Background: Muscle fatigue has been reported as a risk factor for the development of performance-related musculoskeletal disorders (PRMD) in musicians. However, little research exists to support this claim. The aim of this study was to investigate whether changes occur in muscle activity patterns during high string performance over a prolonged playing period, and whether this is influenced by PRMD. Methods: High string musicians were divided into a PRMD and a non-PRMD group. They played a chromatic scale pre and post and a self-chosen “hard” (Borg scale 16-17) piece of music for one hour. Electromyography data recorded from arm, shoulder and trunk muscles was analyzed: the amplitude to measure muscle activity characteristics and the lower frequency to measure muscle fatigue. Differences between and within groups and the frequency spectrum were analyzed using linear mixed models. Results: Fifteen musicians participated (7 PRMD: 22.8 years, 2 male/5 female and 8 non-PRMD: 34.3 years, 2 male/6 female). Changes in muscle activation patterns were observed between and within both groups, however changes varied significantly depending on group affiliation. Significant low frequency spectrum changes between groups were observed in overall muscles of the right arm (p=0.04) and left forearm flexors (p=0.05) following one hour of playing. Conclusions: Muscle activity and frequency spectrum shifts differ in high string musicians with and without PRMD, suggesting possible differential muscle fatigue effects between the groups

A Physiotherapeutic Approach to Musicians' Health – Data From 614 Patients From a Physiotherapy Clinic for Musicians (INAP/O)

Currently, the treatment of musicians is an interprofessional approach. Playing-related health complaints may impact the performance of a musician. In Germany, a medical consulting hour for musicians exists, but those for athletes in sports medicine are not so common. The diagnosing and treatment procedure within the physiotherapy consultation for musicians follows a specific concept-b and requires knowledge of instruments and musician-specific complaints. Based on the consulting hour in a clinic in Osnabrueck, 614 case reports were part of this sample, of which 558 data sets were complete. The focus of the analysis is the instrument and the primary complaint. Also, the type of therapy is characterized, and the amount is calculated. Primary complaints of musicians, in general, are found most frequently in the spine and upper extremity. Musician complaints are different between instruments. Instrumentalists have a significantly higher chance to suffer from a primary complaint in the area of the upper extremity. Furthermore, the groups without an instrument (e.g., singing or dancing) are developing complaints in the anatomical area which they primarily use. Therefore, these types of therapy were used: physiotherapy, manual therapy, and osteopathy with an average of 5.9 treatment units. This study underpinned the importance of musician-specific physiotherapy as a profession to treat musicians. Also, an interdisciplinary approach is necessary to treat all aspects of complaints

Prospectus, February 4, 1987

https://spark.parkland.edu/prospectus_1987/1003/thumbnail.jp

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

Prospectus, December 10, 1986

https://spark.parkland.edu/prospectus_1986/1033/thumbnail.jp

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

BACKGROUND: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. RESULTS: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. CONCLUSION: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes

A three-marker protein biosignature distinguishes tuberculosis from other respiratory diseases in Gambian children

BACKGROUND: Our study aimed to identify a host cytokine biosignature that could distinguish childhood tuberculosis (TB) from other respiratory diseases (OD). METHODS: Cytokine responses in prospectively recruited children with symptoms suggestive of TB were measured in whole blood assay supernatants, harvested after overnight incubation, using a Luminex platform. We used logistic regression models with Least Absolute Shrinkage and Selection Operator (LASSO) penalty to identify the optimal biosignature associated with confirmed TB disease in the training set. We subsequently assessed its performance in the test set. FINDINGS: Of the 431 children included in the study, 44 had bacteriologically confirmed TB, 60 had clinically diagnosed TB while 327 had OD. All children were HIV-negative. Application of LASSO regression models to the training set (n = 260) resulted in the combination of IL-1ra, IL-7 and IP-10 from unstimulated samples as the optimally discriminant cytokine biosignature associated with bacteriologically confirmed TB. In the test set (n = 171), this biosignature distinguished children diagnosed with TB disease, irrespective of microbiological confirmation, from OD with area under the receiver operator characteristic curve (AUC) of 0•74 (95% CI: 0•67, 0•81), and demonstrated sensitivity and specificity of 72•2% (95% CI: 60•4, 82•1%) and 75•0% (95% CI: 64•9, 83•4%) respectively, with its performance independent of their age group and their age- and sex-adjusted nutritional status. INTERPRETATION: This novel biosignature of childhood TB derived from unstimulated supernatants is promising. Independent validation with further optimisation will improve its performance and translational potential. FUNDING: Steinberg Fellowship (McGill University); Grand Challenges Canada; MRC Program Grant