COMPOSITE NONPARAMETRIC TESTS IN HIGH DIMENSION

This dissertation focuses on the problem of making high-dimensional inference for two or more groups. High-dimensional means both the sample size (n) and dimension (p) tend to infinity, possibly at different rates. Classical approaches for group comparisons fail in the high-dimensional situation, in the sense that they have incorrect sizes and low powers. Much has been done in recent years to overcome these problems. However, these recent works make restrictive assumptions in terms of the number of treatments to be compared and/or the distribution of the data. This research aims to (1) propose and investigate refined small-sample approaches for high-dimension data in the multi-group setting (2) propose and study a fully-nonparametric approach, and (3) conduct an extensive comparison of the proposed methods with some existing ones in a simulation. When treatment effects can meaningfully be formulated in terms of means, a semiparametric approach under equal and unequal covariance assumptions is investigated. Composites of F-type statistics are used to construct two tests. One test is a moderate-p version – the test statistic is centered by asymptotic mean – and the other test is a large-p version asymptotic-expansion based finite-sample correction for the mean of the test statistic. These tests do not make any distributional assumptions and, therefore, they are nonparametric in a way. The theory for the tests only requires mild assumptions to regulate the dependence. Simulation results show that, for moderately small samples, the large-p version yields substantial gain in the size with a small power tradeoff. In some situations mean-based inference is not appropriate, for example, for data that is in ordinal scale or heavy tailed. For these situations, a high-dimensional fully-nonparametric test is proposed. In the two-sample situation, a composite of a Wilcoxon-Mann-Whitney type test is investigated. Assumptions needed are weaker than those in the semiparametric approach. Numerical comparisons with the moderate-p version of the semiparametric approach show that the nonparametric test has very similar size but achieves superior power, especially for skewed data with some amount of dependence between variables. Finally, we conduct an extensive simulation to compare our proposed methods with other nonparametric test and rank transformation methods. A wide spectrum of simulation settings is considered. These simulation settings include a variety of heavy tailed and skewed data distributions, homoscedastic and heteroscedastic covariance structures, various amounts of dependence and choices of tuning (smoothing window) parameter for the asymptotic variance estimators. The fully-nonparametric and the rank transformation methods behave similarly in terms of type I and type II errors. However, the two approaches fundamentally differ in their hypotheses. Although there are no formal mathematical proofs for the rank transformations, they have a tendency to provide immunity against effects of outliers. From a theoretical standpoint, our nonparametric method essentially uses variable-by-variable ranking which naturally arises from estimating the nonparametric effect of interest. As a result of this, our method is invariant against application of any monotone marginal transformations. For a more practical comparison, real-data from an Encephalogram (EEG) experiment is analyzed

Periodic Catatonia Marked by Hypercortisolemia and Exacerbated by the Menses: A Case Report and Literature Review

Kahlbaum first described catatonia; later Kraepelin, Gjessing, and Leonhard each defined periodic catatonia differently. A 48-year-old female with catatonia, whose grandmother probably died from it, was prospectively followed for \u3e4 years in a US psychiatric state hospital. Through 4 catatonic episodes (one lasting 17 months) there were menstrual exacerbations of catatonia and increases in 4 biological variables: (1) creatine kinase (CK) up to 4,920 U/L, (2) lactate dehydrogenase (LDH) up to 424 U/L, (3) late afternoon cortisol levels up to 28.0 mcg/dL, and (4) white blood cell (WBC) counts up to 24,200/mm3 with neutrophilia without infections. Records from 17 prior admissions documented elevations of WBC and LDH and included an abnormal dexamethasone suppression test (DST) which normalized with electroconvulsive therapy. Two later admissions showed CK and WBC elevations. We propose that these abnormalities reflect different aspects of catatonic biology: (1) the serum CK, the severity of muscle damage probably exacerbated by the menses; (2) the hypercortisolemia, the associated fear; (3) the leukocytosis with neutrophilia, the hypercortisolemia; and (4) the LDH elevations, which appear to be influenced by other biological abnormalities. Twentieth-century literature was reviewed for (1) menstrual exacerbations of catatonia, (2) biological abnormalities related to periodic catatonia, and (3) familial periodic catatonia

Volleyball Overhead Swing Volume and Injury Frequency over the Course of a Season

Background: Overuse injuries are common in volleyball; however, few studies exist that quantify the workload of a volleyball athlete in a season. The relationship between workload and shoulder injury has not been extensively studied in women\u27s collegiate volleyball athletes. Hypothesis/Purpose: This study aims to quantify shoulder workloads by counting overhead swings during practice and matches. The purpose of the current study is to provide a complete depiction of typical overhead swings, serves, and hits, which occur in both practices and matches. The primary hypothesis was that significantly more swings will occur in practices compared to matches. The secondary hypothesis was that greater swing volume and greater musculoskeletal injury frequency will occur in the pre-season than during the season. Study Design: Prospective cohort. Methods: Researchers observed practice and match videos and counted overhead serves and attacks of 19 women\u27s collegiate volleyball players for two seasons. Serves, overhead hits, and total swings (serves + hits) were the dependent variables; event (matches and practice) along with position (defensive specialists, setter, outside hitter, and middle blocker) were the independent variables. Musculoskeletal injury frequency and swing volume workload were compared across pre-season and competitive season time periods. Results: Across all positions except outside hitters twice as many total swings occurred in practices compared to matches (p = .002) resulting in an average of 19 (CI95 16.5, 21.5) more swings in practice than in matches. The average number of total swings during the pre-season 47.1 (CI95 44.1, 50.1) was significantly greater than average swings per session during the competitive season 37.7 (CI95 36.4, 38.9) (p \u3c 0.001) resulting in a mean difference of 9.4 (CI95 6.1, 12.7) swings. The number of athletes limited in participation or out due to a musculoskeletal injury during the pre-season (2.9%) was greater than during the season (1.1%) (p = 0.042). Conclusion: These findings support the primary hypothesis that women\u27s collegiate volleyball athletes swing more during practices than in matches. The higher average number of serves in the pre-season and the greater frequency of musculoskeletal injuries requiring participation restriction or removal from participation suggest that a concordant relationship may exist between workload and injury variables. Level of Evidence: 2

Opioid and Non-Opioid Prescribing Rates for Ankle Fractures in Emergency Departments across the United States between 2006 and 2015

This presentation describes the percentage of patients prescribed a controlled and non-controlled medication in an United States Emergency Department for a diagnosed ankle fracture

Timing and Amount of Physical Therapy Treatment are Associated with Length of Stay in the Cardiothoracic ICU

Significant variability exists in physical therapy early mobilization practice. The frequency of physical therapy or early mobilization of patients in the cardiothoracic intensive care unit and its effect on length of stay has not been investigated. The goal of our research was to examine variables that influence physical therapy evaluation and treatment in the intensive care unit using a retrospective chart review. Patients (n = 2568) were categorized and compared based on the most common diagnoses or surgical procedures. Multivariate semi-logarithmic regression analyses were used to determine correlations. Differences among patient subgroups for all independent variables other than age and for length of stay were found. The regression model determined that time to first physical therapy evaluation, Charlson Comorbidity Index score, mean days of physical therapy treatment and mechanical ventilation were associated with increased hospital length of stay. Time to first physical therapy evaluation in the intensive care unit and the hospital, and mean days of physical therapy treatment associated with hospital length of stay. Further prospective study is required to determine whether shortening time to physical therapy evaluation and treatment in a cardiothoracic intensive care unit could influence length of stay

Efficacy of Stem Cell Allograft in Maxillary Sinus Bone Regeneration: A Randomized Controlled Clinical and Blinded Histomorphometric Study

Purpose: This study aimed to evaluate the quality and quantity of newly generated bone in the maxillary sinus grafted with stem cell-based allograft material. Methods: This study was a single site, prospective, blinded, randomized, and controlled clinical trial. Eleven subjects with 18 edentulous posterior maxillary sites requiring sinus augmentation for delayed implant placement using a lateral window approach were enrolled. At the time of sinus augmentation, test sinus was grafted with stem cell-based allograft (Osteocel Plus; NuVasive Therapeutics), while the control sinus was grafted with conventional cortico-cancellous allograft (alloOss; ACE Surgical). Cone beam computer tomography (CBCT) scan was taken before and 14 weeks post-sinus augmentation procedure, i.e., 2 weeks before implant placement. Thirty-six trephined core bone biopsies were harvested from the anterior and posterior grafted lateral-window osteotomy sites at the time of implant placement. Results: The results showed a statistically significant difference in the vital bone percentage between the test and the control groups at the posterior grafted sites (p = 0.03). There was no significant difference in the percentage of vital bone between the anterior and posterior grafted sites within the test and control groups (p \u3e .05). The CBCT analysis showed that the maxillary sinuses at the posterior grafted sites were statistically wider than those at the anterior grafted sites in both groups (p \u3c .05). Conclusions: Different allograft bone materials can be used in the maxillary sinus augmentation procedures. Stem cell allograft has more osteogenic potential with a better outcome in the wide posterior sinus

A Guide for Using NIH Image J for Single Slice Cross-Sectional Area and Composition Analysis of the Thigh from Computed Tomography

Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent contribution of each region to the total mid-thigh area. Inter-software correlation coefficients ranged from R2 = 0.92–0.99 for all specific area comparisons measured using the Image J method compared to SliceOmatic. We recommend reporting individual HU ranges for all areas measured. Although HU range 0–100 includes the majority of skeletal muscle area, HU range -29 to 150 appears to be the most inclusive for quantifying total thigh muscle. Reporting all HU ranges is necessary to determine the relative contribution of each, as they may be differentially affected by age, obesity, disease, and exercise. This standardized operating procedure will facilitate consistency among investigators reporting computed tomography characteristics of the thigh on single slice images. Trial Registration: ClinicalTrials.gov NCT02308228

Opioid and Non-Opioid Prescribing Rates for Ankle Fractures in Emergency Departments Across the United States Between 2006 and 2015

Context: An ankle fracture is a common injury observed in the Emergency Department (ED) and is often treated conservatively or surgically, depending on whether the fracture is stable. Opioids provide value for the management of acute musculoskeletal pain. However, prolong opioid use is associated with well-known consequences in the United States such as dependence, abuse and/or misuse. Considering these concerns and the effectiveness of non-pharmacological interventions for the treatment of acute pain, it is critical to identify the prescribing patterns for patients diagnosed with an ankle fracture in the ED. Objective: Describe the percentage of patients prescribed a scheduled and non-controlled medication in the ED. Methods: This was a secondary analysis of the publicly available data collected through the National Hospital Ambulatory Medical Care Survey from 2006-2015. Data analyzed using the sampled visit weight, yielding an unbiased national estimate of ED percentages. Due to the complex sample design, sampling errors were determined using SAS software. Results: From 2006-2015, 86.9% of patients presenting with an ankle fracture received medication during their ED visit. Among those prescribed a medication, 63.02% were prescribed a controlled substance and 34.29% were prescribed a non-controlled substance. The majority of the controlled substances were given to patients between the ages of 25-64. Conclusion: Approximately 2 out of 3 patients diagnosed with an ankle fracture in the ED received a controlled substance. The majority of these given to young-adults. Other effective non-pharmacological interventions should be explored to prevent the risk of the well-known consequences associated with opioid use. Word Count: 25

Metformin Blunts Muscle Hypertrophy in Response to Progressive Resistance Exercise Training in Older Adults: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial: The MASTERS Trial

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double-blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p \u3c .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228