109 research outputs found
Evaluation of the tuberculosis-molecular bacterial load assay for tuberculosis diagnosis and monitoring response to standard anti-tuberculosis therapy
No full textTuberculosis (TB) is a difficult disease to treat, requiring a minimum of six months on a combination of four antibiotics. This thesis reports the first systematic evaluation of the St Andrews' developed RNA-based tuberculosis-Molecular Bacterial Load Assay (TB-MBLA) for its accuracy to diagnose tuberculosis and measure treatment response in comparison to current standard-of-care tests. Presumptive TB patients were enrolled in Uganda and assessed for TB using TB-MBLA versus Xpert MTB/RIF Ultra (Xpert-Ultra) and stained smear fluorescent microscopy (SSM-FM) using sputum MGIT culture as the gold standard and reference test. Out of the 210 presumptive cases, 129 (61.4%) participants tested TB positive on the Xpert-Ultra in the sputum cohort and they were enrolled into the treatment arm and consequently monitored for six months. At baseline, 6/210 (2.9%) sputum MGIT culture results were indeterminate due to contamination, and they were excluded from the calculation of the sensitivity, specificity, and predictive values.
Sensitivity for TB-MBLA and Xpert-Ultra (95%CI) was 99%(95-100) which was higher compared to 76%(65-83) for SSM-FM. TB-MBLA specificity at 90%(83-96) was higher than the 76%(68-86) for Xpert-Ultra but less than 98%(93-100) for SSM-FM. In the treatment follow-up arm, TB positivity rates reduced for all tests. TB-MBLA positivity reduction was consistent with that of the MGIT culture but different from that of Xpert-Ultra which occurred remarkably slower. Consequently, 31 participants were still Xpert-Ultra positive at the end treatment course. Three-month post treatment follow-up of the 31 Xpert-Ultra positive cases revealed no TB both clinically and on TB-MBLA and MGIT tests. In the stool cohort, TB-MBLA detected TB in 57/100 participants including 49 who were confirmed positive for pTB on sputum MGIT culture. Fifty-seven percent (57%) of the indeterminate stool culture were positive on TB-MBLA. The findings prove that TB-MBLA's potential utility as both a diagnostic and treatment monitoring tool of TB in research and routine healthcare."This Ph.D. was funded on the European and Developing Countries Clinical trials Partnership (EDCTP-2) PanACEA II (Grant number: TR1A2015-1102), Makerere University Research and innovation Fund (MakRIF), the University of St Andrews, St Leonards Scholarship; the Infectious Diseases Institute through the Health and Innovation Impact project, the Lung MicroCHIP (Grant number: U01 HL098964), K24 (Grant number: K24 HL087713), and the Scottish Funding Council (SCF)-Global Challenges Research Fund (GCRF). Practical execution of this work would not have been possible without the financial support from the mentioned sponsors, to whom I am incredibly grateful."--Fundin
Conditional inference
No full textDeposited with permission of the author. © 1984 Dr. John Musisi Senyonyi-MubiruConditional inference is a branch of statistical inference in which observed data is reduced using either sufficient or ancillary statistics. This often simplifies inference about the parameters. In comparison to full likelihood methods, conditional inference theory’s performance still needs validating in many areas. Some of these are the concern of this thesis.
While the definition of an ancillary statistic in single parameter models is unequivocal, the presence of accessory (or nuisance) parameters in a model presents problems in defining an ancillary statistic. Statistical literature abounds with definitions of ancillarity in this case. Some of the commonest and most useful of these are discussed and shown to be interrelated. This facilitates the choice of the strongest eligible ancillary in a problem, i.e. that which offers the biggest reduction of the sample space.
The Pitman-Morgan test for variance ratios in bivariate normal populations with unknown correlation coefficient is shown to be a conditional test. We condition on sufficient statistics for the accessory parameters to eliminate them. The test statistic is then derived as an ancillary statistic for the accessory parameters.
When a probability model depends on a number of accessory parameters which increases with the sample size, estimation methods based on the full likelihood will often be inconsistent. Using a partial likelihood instead has been suggested. Local maximum partial likelihood estimators are shown to exist, and to be consistent and asymptotically normal under mild conditions. These results also cover conditional and marginal likelihoods, thus considerably strengthening earlier results in this area.
In planning statistical inferences, it is useful to choose a sampling scheme which provides only the essential data to our inferences. Jagers’ lemma proposes very general conditions under which maximum likelihood estimation from a subset of the data is identical with that from the full data. However, the lemma is incorrect as given. We show that an additional sufficiency condition repairs the lemma. It is further shown that this lemma cannot be extended to general exponential families
In Vitro Studies on Theileria-Infected Lymphoblastoid Cell Lines
No full textA review of literature of the history of the development of Theileria-cell culture and studies on Theileria-infected lymphoblasts was carried out. A need for a systematic study of characteristics that might help identification of Theileria cell-lines as well as the relationship between Theileria and the host-cell in vitro was noted. As a result, a study of the characteristics of Theileria- infected cell-lines and the relationship between Theileria and the host lymphoblast cell was undertaken. Five celllines isolated by the author in Kenya (one infected with T. lawrencei in buffalo cells; three infected with T. lawrencei and one with T. parva in cattle cells) together with four cell-lines (one with T. narva and three with T. annulata in cattle cells) previously isolated by workers in East Africa and Iran were used in the study. Electron microscopic studies on the relationship of T. annulata, T. parva and T. lawrencei with the host-cell revealed a close association of the parasite with the hostcell in that the host-cell treated the parasite in a way similar to its own nucleus by forming nucleopore-1 ike structures with the parasite membrane, and during host-cell division the parasite was aligned along the mitotic spindle fibrils very much in the same way as the host-cell chromosomes were. A very active Golgi apparatus was observed in all Theileria-infected lymphoblasts. No ultrastructural differentiating features between T. parva, T. lawrencei and T. annulata parasites could be found in the Theilerla- infected lymphoblasts maintained in vitro. Studies on isoenzyme variants between the various Theileria-infected cell-lines revealed only two enzymes that could be distinguished on a Theileria-species basis. These were glucose phosphate isomerase and glyceraldehyde phosphate dehydrogenase. The importance of the isoenzyme results is discussed. There were no significant differences between all cattle Theileria-infected cell-lines with regard to percentages of cells parasitized, cells in mitosis and multinucleate cells or the mean schizont nuclear number. There were, however, significant differences between cattle Theileria-infected cells and buffalo Theileria-infected cells. The significance of these findings in relation to characterization of cell-lines is discussed
REDUCED PSYCHEDELIC EFFECTS OF KETAMINE INFUSION AFTER ELECTROCONVULSIVE THERAPY: A REPORT ON THREE CASES.
No full textPsychedelic side effects of ketamine limit its use for the treatment of suicide ideations. Psychedelic effects after ketamine infusion were assessed in two patients received prior electroconvulsive therapy (ECT) and one who had not. Patients who received ECT prior to the infusion had lower mean scores on all domains of the hallucinogen rating scale compared to the patient who did not receive prior ECT. Confirming and understanding this association is needed through more rigorous research methods
Biografi Ngartini Huang Sebagai Musisi Guzheng di Kota Medan
No full textThis research is entitled "Nartini Huang's Biography as a Guzheng Musician in Medan
City". This paper discusses Ngartini Huang's biography of playing Guzheng until he is
proficient and his process of preserving Guzheng. The method used is a qualitative
method which is a description of the data that has been collected. For this reason, in
collecting data the authors carried out field work which included several aspects
including: interviews, visual documentation, and video recording. Then the author uses
the theory of Biographical Anthology of Biographical Authors (A. Baskara, 1999:34),
and the theory of musicians The Anthropology Of Music by Alan P. Merriam, (1964:123-
125). The results showed that Ngartini Huang was initially attracted to Guzheng through
watching films and then studied with Guzheng's teachers and professors and with
Guzheng's senior practitioners and participated in various Guzheng performances in
Indonesia and China. To preserve Guzheng, Ngartini Huang besides actively playing
Guzheng in various places, also established a Jade Music School in Medan City which
specifically teaches Guzheng and Pipa.106 HalamanSkripsi Sarjan
Biografi Ngartini Huang Sebagai Musisi Guzheng di Kota Medan
No full textThis research is entitled "Nartini Huang's Biography as a Guzheng Musician in Medan
City". This paper discusses Ngartini Huang's biography of playing Guzheng until he is
proficient and his process of preserving Guzheng. The method used is a qualitative
method which is a description of the data that has been collected. For this reason, in
collecting data the authors carried out field work which included several aspects
including: interviews, visual documentation, and video recording. Then the author uses
the theory of Biographical Anthology of Biographical Authors (A. Baskara, 1999:34),
and the theory of musicians The Anthropology Of Music by Alan P. Merriam, (1964:123-
125). The results showed that Ngartini Huang was initially attracted to Guzheng through
watching films and then studied with Guzheng's teachers and professors and with
Guzheng's senior practitioners and participated in various Guzheng performances in
Indonesia and China. To preserve Guzheng, Ngartini Huang besides actively playing
Guzheng in various places, also established a Jade Music School in Medan City which
specifically teaches Guzheng and Pipa.106 HalamanSkripsi Sarjan
Recommended from our members
Reproducibility of the ribosomal RNA synthesis ratio in sputum and association with markers of mycobacterium tuberculosis burden
No full textThe MIND-IHOP study was funded by the IHOP grant (NIH R01 HL090335), Lung MicroCHIP grant (NIH U01 HL098964), and K24 grant (NIH K24 HL087713). These sources provided the funding to support participant enrollment and specimen collection. Emmanuel Musisi was supported by a scholarship from the Pulmonary Complications of AIDS Research Training Program (NIH D43 TW009607). N.D.W., R.M.S., J.L.D., and P.N. acknowledge funding from the U.S. National Institutes of Health (1R01AI127300-01A1). N.D.W. and M.I.V. acknowledge funding from the U.S. National Institutes of Health (1R21AI135652-01). N.D.W. acknowledges funding from Veterans Affairs (1IK2CX000914-01A1 and 1I01BX004527-01A1) and from the Doris Duke Charitable Foundation Clinical Scientist Development Award.There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. Importance This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.Peer reviewe
Recommended from our members
High Mycobacterium tuberculosis bacillary loads detected by tuberculosis molecular bacterial load assay in patient stool : a potential alternative for nonsputum diagnosis and treatment response monitoring of tuberculosis
No full textFunding: Emmanuel’s doctoral research is supported by European and Developing countries Clinical Trial Partnership (EDCTP)-funded PanACEA II studentship (TR1A2015-1102), and the University of St Andrews St Leonards scholarship. Funding from the Infectious Diseases Institute, Makerere University to Mr Emmanuel Musisi and Dr Abdul Sessolo through Health and Innovation Impact project supported collection of specimens. Enrolment was funded by the Lung MicroCHIP (NIH: U01 HL098964) and K24 (NIH: K24 HL087713) grants through Professor Laurence Huang. Funding from the Scottish Funding Council (SCF)-Global401 Challenges Research Fund (GCRF) supported the TB-MBLA processing of the samples.Not all patients produce sputum, yet most available TB tests use sputum. We investigated the utility of a novel RNA-based quantitative test, the tuberculosis molecular bacterial load assay (TB-MBLA), for the detection and quantification of Mycobacterium tuberculosis in stool. Stools from 100 adult individuals were treated with OMNIgene-sputum reagent and tested using Xpert MTB/RIF ultra (Xpert ultra), auramine O smear microscopy (smear), mycobacterial growth indicator tube (MGIT), and Lowenstein-Jensen (LJ) cultures. The remaining portions were frozen at −20°C and later tested by TB-MBLA. MGIT sputum culture was used as a TB confirmatory test and reference for stool tests. Sixty-one of 100 participants were already confirmed TB positive by MGIT sputum culture, 20 (33%) of whom were HIV coinfected. TB-MBLA detected M. tuberculosis in 57/100 stool samples, including 49 already confirmed for TB. The mean bacterial load measured by stool TB-MBLA was 5.67 ± 1.7 log10 estimated CFU (eCFU) per mL in HIV-coinfected participants, which was higher than the 4.83 ± 1.59 log10 eCFU per mL among the HIV-negative participants (P = 0.04). The sensitivities (95% confidence intervals [CI]) of stool assays were 80% (68 to 89) and 90% (79 to 98) for TB-MBLA and Xpert ultra, which were both higher than the 44% (32 to 58), 64% (51 to 76), and 62% (45 to 77) for smear, MGIT, and Lowenstein-Jensen (LJ) stool cultures, respectively. The specificity (95% CI) of stool assays was highest for smear, at 97% (87 to 100), followed by Xpert ultra at 91% (76 to 98), TB-MBLA at 79% (63 to 90), LJ at 80% (64 to 91), and MGIT at 62% (45 to 77). Twenty-six percent of MGIT and 21% of LJ stool cultures were indeterminate due to contamination. Detection and quantification of viable M. tuberculosis bacilli in stool raises its utility as an alternative to sputum as a sample type for TB diagnosis.Peer reviewe
Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy : a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda
No full textFunding: Emmanuel Musisi’s doctoral research was supported by the European and Developing Countries Clinical Trial Partnership (EDCTP)-funded PanACEA II studentship (grant number TR1A2015-1102) and the University of St Andrews St Leonards scholarship. Funding from Makerere University Research and Innovation Fund (MAKRIF) by the Government of Uganda to Emmanuel Musisi and Samuel Wamutu supported collection and processing of specimens. Enrolment was funded by NIH R01 HL128156 and NIH R01 HL143998 grants.BACKGROUND: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. METHODS: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. FINDINGS: Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27-44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95-100]) but the specificity was higher for TB-MBLA (90% [83-96]) than for Xpert-Ultra (78% [68-86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65-83]) but higher specificity (98% [93-100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80-100) and was 100% (95% CI 86-100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative. INTERPRETATION: TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. FUNDING: European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.Peer reviewe
Fashion Streetwear Sebagai Penunjang Musisi Indie di Kota Bandung (1990-2004)
No full textThis thesis is titled "Fashion streetwear as a support for indie musicians in the city of Bandung; 1990-2008". The Focus of the discussion is how fashion streetwear can be a support in the sustainbility of indie musicians in the city of Bandung. This research uses a historical method in which there are have several work steps such as field studies, literature studies, and interviews as supporting instruments. The historical method has four stages of work namely heuristics,criticism, interpretation, and historiography. The method the author uses as an analytical tool to dissect the problems discussed plus the help of other scientific concepts such as sociology, economics, and communication. The fact found is that, streetwear fashion began to develop in the City of Bandung in 1990's. The driving factors for the growth of this fashion trend include the development of indie music, and the incresing independent spirit in Bandung which eventually triggers the emergence of local fashion brands in Bandung, to become dominant culture for the city's young people and consistently supporting indie musicians in the Bandung City
- …
