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Empirical Evidence for Synchrony in the Evolution of TB Cases and HIV+ Contacts among the San Francisco Homeless
Mojdeh Mohtashemi,L. Masae Kawamura
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0008851
Abstract: The re-emergence of tuberculosis (TB) in the mid-1980s in many parts of the world, including the United States, is often attributed to the emergence and rapid spread of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Although it is well established that TB transmission is particularly amplified in populations with high HIV prevalence, the epidemiology of interaction between TB and HIV is not well understood. This is partly due to the scarcity of HIV-related data, a consequence of the voluntary nature of HIV status reporting and testing, and partly due to current practices of screening high risk populations through separate surveillance programs for HIV and TB. The San Francisco Department of Public Health, TB Control Program, has been conducting active surveillance among the San Francisco high-risk populations since the early 1990s. We present extensive TB surveillance data on HIV and TB infection among the San Francisco homeless to investigate the association between the TB cases and their HIV+ contacts. We applied wavelet coherence and phase analyses to the TB surveillance data from January 1993 through December 2005, to establish and quantify statistical association and synchrony in the highly non-stationary and ostensibly non-periodic waves of TB cases and their HIV+ contacts in San Francisco. When stratified by homelessness, we found that the evolution of TB cases and their HIV+ contacts is highly coherent over time and locked in phase at a specific periodic scale among the San Francisco homeless, but no significant association was observed for the non-homeless. This study confirms the hypothesis that the dynamics of HIV and TB are significantly intertwined and that HIV is likely a key factor in the sustenance of TB transmission among the San Francisco homeless. The findings of this study underscore the importance of contact tracing in detection of HIV+ individuals that may otherwise remain undetected, and thus highlights the ever-increasing need for HIV-related data and an integrative approach to monitoring high-risk populations with respect to HIV and TB transmission.
Early Detection of Tuberculosis Outbreaks among the San Francisco Homeless: Trade-Offs Between Spatial Resolution and Temporal Scale
Brandon W. Higgs, Mojdeh Mohtashemi, Jennifer Grinsdale, L. Masae Kawamura
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0001284
Abstract: Background San Francisco has the highest rate of tuberculosis (TB) in the U.S. with recurrent outbreaks among the homeless and marginally housed. It has been shown for syndromic data that when exact geographic coordinates of individual patients are used as the spatial base for outbreak detection, higher detection rates and accuracy are achieved compared to when data are aggregated into administrative regions such as zip codes and census tracts. We examine the effect of varying the spatial resolution in the TB data within the San Francisco homeless population on detection sensitivity, timeliness, and the amount of historical data needed to achieve better performance measures. Methods and Findings We apply a variation of space-time permutation scan statistic to the TB data in which a patient's location is either represented by its exact coordinates or by the centroid of its census tract. We show that the detection sensitivity and timeliness of the method generally improve when exact locations are used to identify real TB outbreaks. When outbreaks are simulated, while the detection timeliness is consistently improved when exact coordinates are used, the detection sensitivity varies depending on the size of the spatial scanning window and the number of tracts in which cases are simulated. Finally, we show that when exact locations are used, smaller amount of historical data is required for training the model. Conclusion Systematic characterization of the spatio-temporal distribution of TB cases can widely benefit real time surveillance and guide public health investigations of TB outbreaks as to what level of spatial resolution results in improved detection sensitivity and timeliness. Trading higher spatial resolution for better performance is ultimately a tradeoff between maintaining patient confidentiality and improving public health when sharing data. Understanding such tradeoffs is critical to managing the complex interplay between public policy and public health. This study is a step forward in this direction.
Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay
Puneet Dewan, Jennifer Grinsdale, Sally Liska, Ernest Wong, Robert Fallstad, L Masae Kawamura
BMC Infectious Diseases , 2006, DOI: 10.1186/1471-2334-6-47
Abstract: Patients seen at six community clinics serving homeless, immigrant, or injection-drug user (IDU) populations were routinely offered IGRA (Quantiferon-TB). Per guidelines, we excluded patients who were <17 years old, HIV-infected, immunocompromised, or pregnant. We reviewed medical records for IGRA results and completion of medical evaluation for TB, and at two clinics reviewed TB screening logs for instances of IGRA refusal or phlebotomy failure.Between November 1, 2003 and February 28, 2005, 4143 persons were evaluated by IGRA. 225(5%) specimens were not tested, and 89 (2%) were IGRA-indeterminate. Positive or negative IGRA results were available for 3829 (92%). Of 819 patients with positive IGRA results, 524 (64%) completed diagnostic evaluation within 30 days of their IGRA test date. Among 503 patients eligible for IGRA testing at two clinics, phlebotomy was refused by 33 (7%) and failed in 40 (8%). Including phlebotomy, laboratory, and personnel costs, IGRA use cost $33.67 per patient tested.IGRA implementation in a routine TB control program setting was feasible and acceptable among homeless, IDU, and immigrant patients in San Francisco, with results more frequently available than the historically described performance of TST. Laboratory-based diagnosis and surveillance for M. tuberculosis infection is now possible.Providers in the United States and Europe have for many years relied on the tuberculin skin test (TST) to detect infection with Mycobacterium tuberculosis in patients. The limitations of the TST are well documented, including placement variability, inter-reader variability, boosting, and difficulty in interpreting results in patients previously vaccinated with bacille Calmette Guerin (BCG) or with non-tuberculosis mycobacterial (NTM) infection. [1,2] Patients may find the test inconvenient because they must return in 48–72 hours for result reading and interpretation. TST use poses operational challenges, such as the training and retraining of numerou
Impact of Isoniazid Resistance-Conferring Mutations on the Clinical Presentation of Isoniazid Monoresistant Tuberculosis
Raymund Dantes, John Metcalfe, Elizabeth Kim, Midori Kato-Maeda, Philip C. Hopewell, Masae Kawamura, Payam Nahid, Adithya Cattamanchi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037956
Abstract: Background Specific isoniazid (INH) resistance conferring mutations have been shown to impact the likelihood of tuberculosis (TB) transmission. However, their role in the clinical presentation and outcomes of TB has not been evaluated. Methods We included all cases of culture-confirmed, INH monoresistant tuberculosis reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005. For cases with stored culture isolates, we used polymerase chain reaction (PCR) testing and gene sequencing to identify INH resistance-conferring mutations, and compared genotypic and phenotypic characteristics. Results Among 101 consecutive cases of INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%) had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with other mutations. The katG S315T mutation was independently associated with high-level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07–2.27), and the inhA-15;c-t promoter mutation was inversely associated with high-level INH resistance (RR 0.43, 95% CI 0.21–0.89). However, specific INH resistance-conferring mutations were not associated with the clinical severity or outcomes of INH monoresistant TB cases. Conclusion These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.
Polyanionic Hexagons: X6n– (X = Si, Ge)
Masae Takahashi
Symmetry , 2010, DOI: 10.3390/sym2041745
Abstract: The paper reviews the polyanionic hexagons of silicon and germanium, focusing on aromaticity. The chair-like structures of hexasila- and hexagermabenzene are similar to a nonaromatic cyclohexane (CH2)6 and dissimilar to aromatic D6h-symmetric benzene (CH)6, although silicon and germanium are in the same group of the periodic table as carbon. Recently, six-membered silicon and germanium rings with extra electrons instead of conventional substituents, such as alkyl, aryl, etc., were calculated by us to have D6h symmetry and to be aromatic. We summarize here our main findings and the background needed to reach them, and propose a synthetically accessible molecule.
La liberté bergsonienne et la responsabilité
Masae Nagase
Meta : Research in Hermeneutics, Phenomenology and Practical Philosophy , 2011,
Abstract: In the Essay Bergson defines personal expression as free. A free act is the expression of the conception of life found in a person’s experience of life. Given that it is different for everyone, it cannot be expressed in language. That is why Bergson considers that the act which is the most free is one that is done without any reason. It can be said that Bergson himself felt the need to ground his conception of responsibility. In the Cours II he states two conditions of responsibility: freedom and discernment. The identity of a person which ensures that freedom is based in the conception of duration found in the Essay. In Matter and Memory Bergson tries to resolve the question of discernment with the help of his theory of memory. Bergson succeeded in solving the problems related to reason and to fanciful decision and solidly established the notion of responsibility while renewing the theory of freedom originally found in the Essay.
Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis
Payam Nahid, Leah G Jarlsberg, Irina Rudoy, Bouke C de Jong, Alon Unger, L Masae Kawamura, Dennis H Osmond, Philip C Hopewell, Charles L Daley
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-1
Abstract: Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.Tuberculosis is a leading cause of death worldwide. According to the World Health Organization (WHO) over 1.7 million people with tuberculosis died in 2008 [1]. Advanced age, male gender, delays in diagnosis and treatment, drug resistance, and co-morbid conditions including HIV co-infection, diabetes, renal disease and COPD, have been associated with increased risk of death in patients with active tuberculosis [2-8]. A substantial proportion of deaths occur during tuberculosis treatment despite patient
Local Particle-Ghost Symmetry  [PDF]
Yoshiharu Kawamura
Journal of Modern Physics (JMP) , 2015, DOI: 10.4236/jmp.2015.612174
Abstract: We study the quantization of systems with local particle-ghost symmetries. The systems contain ordinary particles including gauge bosons and their counterparts obeying different statistics. The particle-ghost symmetries are new type of fermionic symmetries between ordinary particles and their ghost partners, different from the space-time supersymmetry and the BRST symmetry. There is a possibility that they are useful to explain phenomena of elementary particles at a more fundamental level, by extension of our systems. We show that our systems are formulated consistently or subsidiary conditions on states guarantee the unitarity of systems, as the first step towards the construction of a realistic fundamental theory.
Use of Whole Genome Sequencing to Determine the Microevolution of Mycobacterium tuberculosis during an Outbreak
Midori Kato-Maeda, Christine Ho, Ben Passarelli, Niaz Banaei, Jennifer Grinsdale, Laura Flores, Jillian Anderson, Megan Murray, Graham Rose, L. Masae Kawamura, Nader Pourmand, Muhammad A. Tariq, Sebastien Gagneux, Philip C. Hopewell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058235
Abstract: Rationale Current tools available to study the molecular epidemiology of tuberculosis do not provide information about the directionality and sequence of transmission for tuberculosis cases occurring over a short period of time, such as during an outbreak. Recently, whole genome sequencing has been used to study molecular epidemiology of Mycobacterium tuberculosis over short time periods. Objective To describe the microevolution of M. tuberculosis during an outbreak caused by one drug-susceptible strain. Method and Measurements We included 9 patients with tuberculosis diagnosed during a period of 22 months, from a population-based study of the molecular epidemiology in San Francisco. Whole genome sequencing was performed using Illumina’s sequencing by synthesis technology. A custom program written in Python was used to determine single nucleotide polymorphisms which were confirmed by PCR product Sanger sequencing. Main results We obtained an average of 95.7% (94.1–96.9%) coverage for each isolate and an average fold read depth of 73 (1 to 250). We found 7 single nucleotide polymorphisms among the 9 isolates. The single nucleotide polymorphisms data confirmed all except one known epidemiological link. The outbreak strain resulted in 5 bacterial variants originating from the index case A1 with 0–2 mutations per transmission event that resulted in a secondary case. Conclusions Whole genome sequencing analysis from a recent outbreak of tuberculosis enabled us to identify microevolutionary events observable during transmission, to determine 0–2 single nucleotide polymorphisms per transmission event that resulted in a secondary case, and to identify new epidemiologic links in the chain of transmission.
Bacterial protein toxins
Elsa Masae Mamizuka
Revista Brasileira de Ciências Farmacêuticas , 2004, DOI: 10.1590/s1516-93322004000200023
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