Browsing by Subject "Research Design and Methods"
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Item Automated Analysis of Electroglottographic Signal in Adductor Spasmodic Dysphonia(2013-01-22) Somanath, Keerthan; Mau, TedINTRODUCTION: The human voice can be evaluated by a variety of methods. Electroglottographic (EGG) signal is produced when vocal fold vibrations produce cyclic fluctuation in the electrical impedance across the larynx. The EGG signal thus reflects the degree of contact between the vocal folds during voice production and provides a measure of voice quality based on phonatory physiology. However, the utility of EGG has been limited because existing methods of EGG signal analysis focus on the evaluation of 2-3 parameters in a segment of sustained vowel production, which does not reflect pathologies more apparent in conversational speech. We hypothesize that the EGG signal can capture perceptually relevant information from continuous speech in adductor spasmodic dysphonia (ADSD), an enigmatic speech disorder. OBJECTIVES: 1. To develop an automated computer algorithm to analyze the EGG signal in continuous dysphonic speech. 2. To identify EGG waveform features that correlate with the perceived quality of vocal strain in ADSD. METHODS: A computer program was created and refined in MATLAB to display and analyze EGG data via a graphical user interface (GUI). An automated peak-detection algorithm was developed using the differentiated EGG signal and used to perform simultaneous multi-parameter analysis on the EGG signal from normal speech and speech in patients with ADSD. Between-group comparisons were made using two-tailed Student's t test. Also, intrasubject comparison was made between strained and less-strained syllables in ADSD speech. RESULTS: A program was successfully written to allow the display and automated analysis of EGG data from samples of continuous dysphonic speech. The program was found to generate data with good internal consistency. Application to normal and ADSD subjects showed that the open quotient parameter was able to distinguish between strained and less-strained syllables with statistical significance (p=0.04). DISCUSSION/CONCLUSION: We have developed a method to analyze EGG signal from samples of continuous dysphonic speech. The numerical and graphical data obtained support the utility of EGG as an objective means to clinically highlight the speech differences between normal subjects and subjects with ADSD. Further testing to establish normative values for the analyzed EGG parameters and their subsequent comparison with patient EGG data is required to affirm their utility for routine clinical voice assessment.Item Comparison of Pre-Transplant Criteria and Outcomes for Living Donor Kidney Transplant Programs in India and the United States(2015-01-26) Bansal, Sukriti; Raja, Hari; Rajora, Nilum; Kher, VijayBACKGROUND: One of the greatest obstacles to treatment of end stage renal disease globally is organ donor shortage. While some nations (i.e. the US), have primarily cadaveric organ donors, developing nations rely heavily on living donors. This project is a comparison of two kidney transplants programs -- one in the US & one in India -- looking at the pre-transplant criteria of each & assessing the patient outcomes. METHODS: This is a cohort study of living donor kidney transplant patients from St. Paul University Hospital in Dallas, TX & kidney transplant patients from Medanta the Medicity in Gurgaon, India. Data for India was collected from a database of all patients who underwent a kidney transplant at Medanta, selected for patients who fit the following criteria: one cohort of patients had been transplanted the previous month (N=29), one cohort had been transplanted one year prior the date of the study (N=29), & one cohort had been transplanted 3 years prior (N=13). Information from the database was used to calculate patient & graft survival rates for the relevant time periods. Data for St. Paul was obtained from the Scientific Registry of Transplant Recipients, which already had the calculated 1 month, 1 year, & 3 year patient and graft survival rates. Information on pre-transplant criteria was obtained from the transplant teams at each respective institution. RESULTS: The majority of medical pre-operative criteria between the two programs are identical. One significant difference is ABO-incompatible transplants are performed at Medanta, while at St. Paul ABO-incompatible donor/recipient pairs are referred for paired donation. Medanta requires all living donors to be related, while St. Paul will accept unrelated donors. The patient survival rates for St. Paul are 100% (1 mo, N=32), 95.23% (1 yr, N=32) and 85.71 % (3 yr, N=21). Graft survival rates are 100% (1 mo, N=32), 95.24% (1 yr, N=32), and 81.82% (3 yr, N=22). The patient survival rates for Medanta are 100% (1 mo., N=29), 100% (1 yr, N=29), and 100% (3 yr, N=13). Graft survival rates are 100% (1 mo. N=29), 100% (1 yr, N=29), and 100% (3 yr, N=13). For all patients transplanted at Medanta, the overall patient survival rate was 98.40% (N=874) and the overall graft survival rate was 98.51% (N=874). Corresponding data wasn't available for St. Paul. CONCLUSION: While it appears that the 3 year survival rates are better for Medanta than for St. Paul, there is a limitation on making conclusions because this data does not encompass the entire program at Medanta. Further study is needed to truly assess if there is a significant difference. The overall conclusion is that transplant programs in both settings have successful outcomes.Item Decreased microRNA-122 Levels with HCV Clearance in HIV-HCV Co-Infections(2013-01-22) Dubin, Perry H.; Yuan, Hejun; Devine, Robert K.; Jain, Mamta K.; Hynan, Kinda S.; Lee, William M.BACKGROUND AND AIMS: Micro RNA-122 (miR-122) is under investigation as a target for direct antiviral agents against the hepatitis C virus (HCV), and as a biomarker for both cancer and acute liver injury. Previous data suggest HCV mono-infection is associated with increased serum miR-122 levels. This study sought to determine outcomes in regard to miR-122 levels following clearance of HCV in human immunodeficiency virus (HIV) co-infected patients. METHODS: Nine HCV-HIV co-infected patients undergoing antiviral therapy were treated with interferon and ribavirin for 48 weeks between January 2009 and March 2011, and had serial miR-122 levels measured in triplicate from serum with mirVanaTM PARISTM kit according to the instructions from the manufacturer (Ambion, AM1556). Values were measured at baseline, 1 week, 4 weeks, end of treatment (EOT; 48 weeks), and at 24 weeks after treatment completion (SVR24). SAS V9.3 was used to analyze these data. Change from baseline (copies/μL) was calculated as Log10 (Baseline)-Log 10(time), where time was 1 week, 4weeks, EOT, and SVR24; a repeated measures ANOVA was used to compare the results over time for the patients. If the ANOVA was found significant, post hoc, pairwise comparisons were used to examine change from baseline across the four time points. RESULTS: Six of nine achieved SVR24, 1 was undetectable at EOT but relapsed, and 2 patients were non-responders. Among the 6 patients achieving SVR, all showed a decrease in miR-122 levels between 0.16 and 1.46 logs, between baseline and SVR24. The ANOVA confirmed a significant decrease in miR-122 levels from 1 week to SVR24 (p=0.0225). Significant pairwise comparisons for change from baseline were found at 1 week versus SVR24 (p=0.0063), 4 weeks versus SVR24 (p=0.0086), and EOT versus SVR24 (p=0.0458). CONCLUSION: Clearance of chronic HCV is associated with decreased miR-122 levels in HIV co-infected patients and was not improved in patients with continued infection who failed to respond to treatment.Item The Impact of Portable Electronic Devices on Attending Rounding Behaviors of Inpatient Internal Medicine Teams at an Academic Medical Center(2014-02-04) Locke, Cameron; Suss, Adina; Barker, Blake; Moran, Brett; Wagner, JamesINTRODUCTION: The advancement of mobile technologies is changing the way medicine is practiced. Portable devices give health care professionals access to electronic resources and patient health records without restricting them to stationary computers. However, little exists in the literature on how these devices impact the rounding behavior of health care teams at academic medical centers. There is general concern that the EHR will compel caregivers to spend less time with their patients; there is significant evidence in a prior unpublished study to support this unintended consequence. In this study the authors sought to identify whether the availability of tablet computers to inpatient internal medicine teams would combine the best of both previous rounding behaviors. METHODS: Research was conducted over a period of 28 days, consisting of observation of internal medicine teams randomized into intervention, who were provided with tablet computers, and control groups. Two observers recorded behaviors on a standardized checklist, which included domains of patient care, EHR use, and distractions. RESULTS: 323 patient encounters were recorded in the context of eighteen health care teams, fourteen control (160 encounters) and four intervention (163 encounters). General characteristics of each arm of the study are summarized below: Variable Control Intervention p-value Tablet Used (y/n) 18.13% 50.31% < 0.0001 Tablet Use Count 0.29 1.18 < 0.0001 Total Tech Use Count 2.01 2.00 0.3637 Tablet Distraction Count 0 0.26 < 0.0001 Total Distraction Count 1.84 2.60 0.0045 % Rounds on Wards 34.38% 71.17% < 0.0001 Time per Patient (minutes) 12.37 10.62 0.0118 Time at Bedside (minutes) 3.28 3.71 0.6358 DISCUSSION: Tablet possession is associated with increased ward rounding with the same level of access to EHR as would be offered by room rounding, shorter time spent discussing each patient, but increased time spent at the patient's bedside. This constellation of findings may suggest increased efficiency. Intervention teams experienced more distractions than control teams, as is expected due to the increased amount of ward rounding. However, the tablets themselves contributed to the number of distractions. These results can shed light on the role that tablet computers will play as we enter the electronic age of medicine.Item Masqueraders for Appendicitis(2015-01-26) Farzal, Zehra; Khan, N.; Cope-Yokoyama, S.; Fischer, A.C.INTRODUCTION: Patients with cystic fibrosis (CF) are often subject to pulmonary infections treated with antibiotics such as aminoglycosides which have the side effect of sensorineural hearing loss (SNHL). Since children with CF are often on prolonged courses and/or higher doses, they are particularly at risk. OBJECTIVE: To review the role of routine hearing screening for SNHL in children with CF who have been on aminoglycoside therapy. DATA SOURCES: PubMed, Cochrane, SCOPUS, and OVID databases REVIEW METHODS: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive PubMed MeSH search of the English language literature with human subjects only was performed to include all indexed years and the search strategy was adapted to the additional databases. Results: Twelve studies (1979-2014) were included in the review. Three of the 12 articles also studied adult CF patients. The study population included 762 children (age range, 5 months-20 years). Objective hearing screening measures included pure tone audiometry (PTA) at standard ± high frequency threshold (12/12), distortion product otoacoustic emissions (DPOAE) (4/12), transient-evoked otoacoustic emissions (1/12), and automated auditory brainstem response (AABR) (1/12). The overall prevalence of SNHL ranged from 0% to 29%. In a subset of children with high levels of exposure, up to 44% had SNHL. Eight studies recommended hearing screening in CF children on aminoglycosides of which 2 studies recommended screening regardless of aminoglycoside exposure. Four studies made no recommendations and in three of these, the children had a short course of aminoglycosides. HFPTA was the most commonly recommended screening measure followed by DPOAEs. CONCLUSION: Hearing screenings are quick and inexpensive measures leading to interventions that can prevent significant cognitive and linguistic developmental difficulties in children secondary to hearing loss. Routine hearing screening in children with CF exposed to aminoglycosides is supported by the current literature based on the high prevalence of SNHL in this population. Future studies should define the optimal timing for hearing screening during and after aminoglycoside therapy.Item One-Pot Measurement of the Kinetic Parameters KI, kinact, and Time-Dependent IC₅₀ for Analysis of Covalent Small Molecule Kinase Inhibitors(2016-01-19) Montalvo, Steven K.; Mondi, Anuja; Westover, Kenneth D.To address the need for the analysis of covalent kinase inhibitors in a high-throughput method, we established a protocol for the facile measurement of kinact and KI utilizing a proprietary off-chip mobility shift assay supplied by PerkinElmer. With this electrophoretic technique, these kinetic parameters, which describe covalent inhibitors better than IC50 measurements, are accurately and reproducibly measured. As a proof of concept measurement, an inhibitor of BMX, compound BMX-IN-1, was shown to have a kinact = 0.0298 ± 0.0024 min-1 and a KI = 0.134 ± 0.021 uM. The industry standard for reporting is kinact/KI and was calculated to be 0.222 ± 0.039 uM-1min-1. To direct medicinal chemists optimizing parameters of covalent inhibitors, simulations of the equations used to fit progress curves were performed in MatLab. These revealed the compelling argument to pursue improved KI before kinact and are discussed further. In addition, some limitations of our assay are presented.Item Searching for Genes of Host Defense(2013-01-22) SoRella, Jeffrey A.; Shi, He-Xin; Wang, Ying; Beutler, Bruce A.Through random mutation of the mouse genome and phenotypic screening of the mutated mice, genes can be identified that are associated with dysfunction in the innate immune system. The strategy proposed works under the knowledge that many genes are involved in the immune system and that random mutation could lead to a change in their genetic code. This mutation can present as a phenotypically abnormal immune system. Once a phenotype is identified, the genome can be analyzed in an attempt to trace the mutated gene responsible for the weakened immune system. One of the elegant aspects of this genetic method is that it does not rely on a hypothesis about how the immune response works. This leads to an unbiased approach where interpretation errors are rarely made. A forward genetic approach is used to create abnormal phenotypes of the innate immune system and then determine the genetic cause. The normal mutation rate is accelerated by the widely used germline mutagen N-ethyl-N-nitrosourea (ENU) to produce an average of 3,000 single nucleotide changes per host leading to an average of 60 coding changes. To produce homozygotes, males of the G1 generation are bred with normal mice of the same strain to yield the G2 generation. Recessive mutations can be found in the G3 generation by a backcross of G2 females with the G1 father. Screening 6 G3 progeny should capture 50% of the mutations in the homozygous form. Phenotypic screening was performed on peritoneal macrophages ex vivo by stimulation with the following toll-like receptor agonists: lipopolysaccharide (TLR4), double stranded RNA (TLR3), triacylated lipoprotein (TLR 1/2), diacylated lipoprotein (TLR 2/6), resiquimod (TLR 7), and unmethylated DNA (TLR 9). The inflammasome pathway was probed by lipopolysaccharide priming followed by stimulation with either nigericin (K+ efflux) or ATP. The secreted TNF-alpha (TLR screen) and IL-1beta (inflammasome screen) were measured by ELISA to determine phenovariance. This research can lead to a deeper understanding of how we combat infection. The study can lead to the development of mutations involved in both the innate and adaptive immune system so autoimmune diseases can also be studied. A long term goal is to identify genes that would render an individual resistant to infection and to study the interaction of these genes.