Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study

BACKGROUND: Inflammatory response following initial improvement with anti-tuberculosis (TB) treatment has been termed a paradoxical reaction (PR). HIV co-infection is a recognised risk, yet little is known about other predictors of PR, although some biochemical markers have appeared predictive. We report our findings in an ethnically diverse population of HIV-infected and uninfected adults. METHODS: Prospective and retrospective clinical and laboratory data were collected on TB patients seen between January 1999-December 2008 at four UK centres selected to represent a wide ethnic and socio-economic mix of TB patients. Data on ethnicity and HIV status were obtained for all individuals. The associations between other potential risk factors and PR were assessed in a nested case-control study. All PR cases were matched two-to-one to controls by calendar time and centre. RESULTS: Of 1817 TB patients, 82 (4.5 %, 95 % CI 3.6-5.5 %) were identified as having a PR event. The frequency of PR was 14.4 % (18/125; 95 % CI 8.2-20.6 %) and 3.8 % (64/1692; 2.9-4.7) for HIV-positive and HIV-negative individuals respectively. There were no differences observed in PR frequency according to ethnicity, although the site was more likely to be pulmonary in those of black and white ethnicity, and lymph node disease in those of Asian ethnicity. In multivariate analysis of the case-control cohort, HIV-positive patients had five times the odds of developing PR (aOR = 5.05; 95 % CI 1.28-19.85, p = 0.028), whilst other immunosuppression e.g. diabetes, significantly reduced the odds of PR (aOR = 0.01; 0.00-0.27, p = 0.002). Patients with positive TB culture had higher odds of developing PR (aOR = 6.87; 1.31-36.04, p = 0.045) compared to those with a negative culture or those in whom no material was sent for culture. Peripheral lymph node disease increased the odds of a PR over 60-fold 4(9.60-431.25, p < 0.001). CONCLUSION: HIV was strongly associated with PR. The increased potential for PR in people with culture positive TB suggests that host mycobacterial burden might be relevant. The increased risk with TB lymphadenitis may in part arise from the visibility of clinical signs at this site. Non-HIV immunosuppression may have a protective effect. This study highlights the difficulties in predicting PR using routinely available demographic details, clinical symptoms or biochemical markers

Potential for non-destructive astrochemistry using the ExoMars PanCam

We investigate the utility of adding a 365 nm ultraviolet (UV) light source to the ExoMars panoramic camera (PanCam) scheduled for launch in 2013. The modification makes it feasible to monitor rover drill cuttings for aromatic organic molecules and provide constraints on polycyclic aromatic hydrocarbons (PAH) as a function of depth to the 2-meter limit of the ExoMars drill. This non-destructive triage allows prioritized deployment of organic detection experiments requiring sample destruction and/or expenditure of non-replaceable resources. Utilizing the Beagle 2 PanCam backup filter wheel fitted with original blue (440 nm), green ( 530 nm), and red ( 670 nm) filters we captured fluorescent images following 365 nm excitation of 3-, 4- and 5-ring PAH species doped on Mars analog peridotite grains. We demonstrate a detection limit for pyrene of 1.5 mu g in granular peridotite doped at pyrene levels of 50 +/- 5 ppm for camera-to-target distance of 1 meter

Engineering Art Galleries

The Art Gallery Problem is one of the most well-known problems in Computational Geometry, with a rich history in the study of algorithms, complexity, and variants. Recently there has been a surge in experimental work on the problem. In this survey, we describe this work, show the chronology of developments, and compare current algorithms, including two unpublished versions, in an exhaustive experiment. Furthermore, we show what core algorithmic ingredients have led to recent successes

Field-induced quantum fluctuations in the heavy fermion superconductor CeCu2Ge2

Quantum-mechanical fluctuations in strongly correlated electron systems cause unconventional phenomena such as non-Fermi liquid behavior, and arguably high temperature superconductivity. Here we report the discovery of a field-tuned quantum critical phenomenon in stoichiometric CeCu2Ge2, a spin density wave ordered heavy fermion metal that exhibits unconventional superconductivity under ~ 10 GPa of applied pressure. Our finding of the associated quantum critical spin fluctuations of the antiferromagnetic spin density wave order, dominating the local fluctuations due to single-site Kondo effect, provide new information about the underlying mechanism that can be important in understanding superconductivity in this novel compound.Comment: Heavy Fermion, Quantum Critical Phenomeno

Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report

The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis

The effects of the Islamic revolution and the gulf war on Iran's economy

The Islamic revolution, followed by the eight-year Gulf war, has caused severe disruption and extensive changes in the structure of the Iranian economy. This thesis is concerned with an analytical study of Iran’s economy In the period from the Shah's western-style modernisation to the Islamic revolution and the war with Iraq. Thus, the thesis provides first, an overview of the economic development and industrialisation activity under the Shah, which glides a yardstick for understanding the post-revolutionary economy. Secondly, the thesis examines the concept of Islamic economics as articulated by the prominent contemporary Shi'i figures that continue to influence the post-revolutionary economic policies. Thirdly, the major part of the thesis devotes considerable attention to the study and evaluation of the post-revolutionary economy, focusing on agriculture, industry, foreign and domestic trade. Islamic balancing, public finance, the oil sector and the oil war. The latter was a determining factor in the continuation of the Gulf war. The appraisal and the overall picture of the post-revolutionary economy makes bleak reading. The negative Impact of the revolution and the war has left Iran with a shattered infrastructure and a moribund industrial base. Unprecedented destruction of wealth, both in human and non-human terms, has further exacerbated the pre-revolutionary economic problems. The politico-religious government has not been able to address the country's economic Ills effectively, partly owing to self -imposed constraints. A lack of active and structured economic policies has adversely affected all sectors of the economy, in particular, agriculture. While facing the daunting task of post-war reconstruction, Iran, more than ever before, is dependent on trading oil in exchange for basic commodities and consumer goods

Trends in utilization and costs of BRCA testing among women aged 18–64 years in the United States, 2003–2014

Purpose We examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors. Methods We estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18–64 years using private claims data and publicly reported revenues from the primary BRCA testing provider. Results The percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013–2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013–2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity. Conclusion The observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae. Modifications to an in vitro chromatin assembly assay are described that allowed a brute force screen of temperature sensitive (ts) yeast strains in order to identify chromatin assembly defective extracts. This screen yielded mutations in genes encoding two ubiquitin protein ligases (E3s): RSP5, and a subunit of the Anaphase Promoting Complex (APC), APC5. Additional modifications are described that allow for a rapid analysis and an in vivo characterization of yeast chromatin assembly mutants, as well as any other mutant of interest. Our analysis suggests that the in vitro and in vivo chromatin assembly assays are responsive to different cellular signals, including cell cycle cues that involve different molecular networks

Reproductive Outcomes Following Ectopic Pregnancy: Register-Based Retrospective Cohort Study

Using Scottish national registry data, Sohinee Bhattacharya and colleagues investigate pregnancy outcomes following ectopic pregnancy in comparison to livebirth, miscarriage, or termination in a first pregnancy