Research Articles (Statistics and Actuarial Science)
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- ItemComparison of zero replacement strategies for compositional data with large numbers of zeros(Elsevier B.V., 2021-03) Lubbe, Sugnet; Filzmoser, Peter; Templ, MatthiasModern applications in chemometrics and bioinformatics result in compositional data sets with a high proportion of zeros. An example are microbiome data, where zeros refer to measurements below the detection limit of one count. When building statistical models, it is important that zeros are replaced by sensible values. Different replacement techniques from compositional data analysis are considered and compared by a simulation study and examples. The comparison also includes a recently proposed method (Templ, 2020) [1] based on deep learning. Detailed insights into the appropriateness of the methods for a problem at hand are provided, and differences in the outcomes of statistical results are discussed.
- ItemPathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis(2023-05) Johannes, Clint; Moremi, Kelebogile E.; Kemp, Merlisa C.; Whati, Lindiwe; Engel- Hills, Penelope; Kidd, Martin; van Toorn, Ronald; Jaftha, Mariaan; Janse van Rensburg, Susan; Kotze, Maritha J.ABSTRACT: Background: Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Methods: Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology- supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise were investigated. Results: PwMS-ON had significantly lower (p < 0.01) disability (Expanded Disability Status Scale) than pwMS not on the program (1.91 ± 0.75 vs 3.87 ± 2.32). A genetic variant in the lipid transporter FABP2 gene (rs1799883; 2445G>A, A54T) was significantly associated (p < 0.01) with disability in pwMS not on the program, but not in pwMS-ON (p = 0.88). Vascular blood flow velocities were lower in the presence of the A-allele. Conclusion: Pathology-supported genetic testing may provide guidance for lifestyle interventions with a significant impact on improved disability in pwMS. Plain Language Summary This study investigated the role of a genetic variant that increases saturated fat absorption and may make people with multiple sclerosis (MS) more susceptible to disability progression. Of 51 people with MS, 19 had followed a program which includes normalization of blood test results and daily intake of unsaturated fatty acids for more than 10 years, while the others had not. The latter group had significantly greater disability than the people who had followed the program, suggesting that the unsaturated fatty acids modulated the effect of the genetic variant. Six MS cases are presented as examples, including a marathon athlete (Case 1) and a patient who showed a dramatic decrease in disability from being wheelchair-bound for 15 years to walking freely (Case 2). Executive Summary: • In order to investigate the conundrum of why some people with multiple sclerosis (pwMS) become disabled while others do not, a cross-sectional interdisciplinary study was initiated from 1996 to the present at Stellenbosch University, to record data into a database regarding genetic variations, blood biochemistry, diet and exercise. Pathology-supported genetic testing (PSGT), a practical method to apply personalized medicine, was implemented to elucidate potential modulation of genetic variations through lifestyle interventions toward prevention of disability in pwMS. • The Gknowmix.org database is used to translate information obtained from a comprehensive study into personalized reports containing guidelines for treatment of pwMS by clinicians and supporting healthcare professionals, which enables P4 medicine: participatory (patient), personalized (scientist), predictive (clinician) and preventive (dietitian). • In the present case–control sub-study, 51 pwMS and 25 controls volunteered for an ultrasound and MRI study. Of these pwMS, 19 had followed the PSGT lifestyle program for more than 10 years, which included normalization of blood biochemistry, dietary intervention and exercise, as well as daily intake of specific supplements (the Rapha Regimen) [3], including unsaturated fatty acids (omega-3 and evening primrose oil). • The 19 pwMS who had followed the program had significantly less disability (p < 0.01), as assessed with the Expanded disability status scale (EDSS), than those who had not followed the program (1.91 ± 0.75 vs 3.87 ± 2.32). Furthermore, in the pwMS who had not followed the program, a genetic variant of a lipid transporter which favors increased absorption of saturated fatty acids, FABP2 rs1799883 (2445G>A, A54T), was associated significantly (p < 0.01) with the EDSS, while in the pwMS who had followed the program there was no association (p = 0.88). There was no difference in allele frequency between pwMS and controls. • Ultrasound assessments showed that higher blood flow velocities in the right common carotid arteries and vertebral arteries were significantly associated with improved EDSS, while the FABP2 rs1799883 variant was associated with decreased blood flow. • In the pwMS, homocysteine was significantly inversely associated with folate intake (p < 0.01). In the controls, saturated/trans fat intake was significantly associated with BMI (p < 0.01). • Six MS cases selected randomly are presented to demonstrate how data integration was instrumental in elucidating how dietary unsaturated fat intake may modulate the effect of FABP2 rs1799883 toward prevention of disability in pwMS who followed the PSGT protocol over more than 10 years. Of these, Case 1 is a marathon athlete, and Case 2 showed a dramatic decrease in EDSS from 7.5 to 2.0 over more than 10 years.
- ItemDoes money "buy" tolerance toward damage-causing wildlife?(Wiley, 2020-07-26) Kansky, Ruth; Kidd, Martin; Fischer, JoernThe Kavango-Zambezi Transfrontier Conservation Area supports large-scale migrations of wildlife that occur in a mixed agri-conservation landscape in five Southern African countries. Human–Wildlife Conflict is a key challenge and understanding the drivers of communities' willingness to coexist with wildlife is thus critical. Community based natural resource management (CBNRM) is a widely used economic approach to foster human-wildlife coexistence with the assumption that monetary benefits can “buy” tolerance by offsetting the disservices of living with wildlife. We tested this assumption and hypothesized that Namibians would be more tolerant towards wildlife than Zambians because they received higher monetary benefits from wildlife. We used the Wildlife Tolerance Model (WTM) as the framework to define tolerance and identify tolerance drivers. We found Namibians tolerance was higher for lion, elephant and hyena but not for kudu and baboon. After controlling for confounding variables of the WTM that could potentially explain differences in tolerance, contrary to expectation, the monetary benefits did not account for higher Namibian tolerance. Instead, only nonmonetary benefits explained the higher tolerance. We used crowding theory to explain this finding, proposing that CBNRM in Namibia and the monetary benefits from the program “crowd in” intrinsic motivation to appreciate and tolerate wildlife.
- ItemVariable contribution identification and visualization in multivariate statistical process monitoring(Elsevier, 2020-01) Rossouw, R. F.; Coetzer, R. L. J.; Le Roux, N. J.Multivariate statistical process monitoring (MSPM) has received book-length treatments and wide spread application in industry. In MSPM, multivariate data analysis techniques such as principal component analysis (PCA) are commonly employed to project the (possibly many) process variables onto a lower dimensional space where they are jointly monitored given a historical or specified reference set that is within statistical control. In this paper, PCA and biplots are employed together in an innovative way to develop an efficient multivariate process monitoring methodology for variable contribution identification and visualization. The methodology is applied to a commercial coal gasification production facility with multiple parallel production processes. More specifically, it is shown how the methodology is used to specify the optimal principal component combinations and biplot axes for visualization and interpretation of process performance, and for the identification of the critical variables responsible for performance deviations, which yielded direct benefits for the commercial production facility.
- ItemInvolvement of the spinal cord in primary mitochondrial disorders : a neuroimaging mimicker of inflammation and ischemia in children(American Journal of Neuroradiology, 2021-02) Alves, C. A. P. F.; Goldstein, A.; Teixeira, S. R.; Martin-Saavedra, J. S.; De Barcelos, I. P.; Fadda, G.; Caschera, L.; Kidd, M.; Gonçalves, F. G.; McCormick, E. M.; Falk, M. J.; Zolkipli-Cunningham, Z.; Vossough, A.; Zuccoli, G.Background and purpose: Little is known about imaging features of spinal cord lesions in mitochondrial disorders. The aim of this research was to assess the frequency, imaging features, and pathogenic variants causing primary mitochondrial disease in children with spinal cord lesions. Materials and methods: This retrospective analysis included patients seen at Children's Hospital of Philadelphia between 2000 and 2019 who had a confirmed diagnosis of a primary (genetic-based) mitochondrial disease and available MR imaging of the spine. The MR imaging included at least both sagittal and axial fast spin-echo T2-weighted images. Spine images were independently reviewed by 2 neuroradiologists. Location and imaging features of spinal cord lesions were correlated and tested using the Fisher exact test. Results: Of 119 children with primary mitochondrial disease in whom MR imaging was available, only 33 of 119 (28%) had available spine imaging for reanalysis. Nineteen of these 33 individuals (58%) had evidence of spinal cord lesions. Two main patterns of spinal cord lesions were identified: group A (12/19; 63%) had white ± gray matter involvement, and group B (7/19; 37%) had isolated gray matter involvement. Group A spinal cord lesions were similar to those seen in patients with neuromyelitis optica spectrum disorder, multiple sclerosis, anti-myelin oligodendrocyte glycoprotein-IgG antibody disease, and leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Group B patients had spinal cord findings similar to those that occur with ischemia and viral infections. Significant associations were seen between the pattern of lesions (group A versus group B) and the location of lesions in cervical versus thoracolumbar segments, respectively (P < .01). Conclusions: Spinal cord lesions are frequently observed in children with primary mitochondrial disease and may mimic more common causes such as demyelination and ischemia.