The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function

The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Analysis of laser radiation using the Nonlinear Fourier transform

Modern high-power lasers exhibit a rich diversity of nonlinear dynamics, often featuring nontrivial co-existence of linear dispersive waves and coherent structures. While the classical Fourier method adequately describes extended dispersive waves, the analysis of time-localised and/or non-stationary signals call for more nuanced approaches. Yet, mathematical methods that can be used for simultaneous characterisation of localized and extended fields are not yet well developed. Here, we demonstrate how the Nonlinear Fourier transform (NFT) based on the Zakharov-Shabat spectral problem can be applied as a signal processing tool for representation and analysis of coherent structures embedded into dispersive radiation. We use full-field, real-time experimental measurements of mode-locked pulses to compute the nonlinear pulse spectra. For the classification of lasing regimes, we present the concept of eigenvalue probability distributions. We present two field normalisation approaches, and show the NFT can yield an effective model of the laser radiation under appropriate signal normalisation conditions

Real-time high-resolution heterodyne-based measurements of spectral dynamics in fibre lasers

Conventional tools for measurement of laser spectra (e.g. optical spectrum analysers) capture data averaged over a considerable time period. However, the generation spectrum of many laser types may involve spectral dynamics whose relatively fast time scale is determined by their cavity round trip period, calling for instrumentation featuring both high temporal and spectral resolution. Such real-time spectral characterisation becomes particularly challenging if the laser pulses are long, or they have continuous or quasi-continuous wave radiation components. Here we combine optical heterodyning with a technique of spatiooral intensity measurements that allows the characterisation of such complex sources. Fast, round-trip-resolved spectral dynamics of cavity-based systems in real-time are obtained, with temporal resolution of one cavity round trip and frequency resolution defined by its inverse (85 ns and 24 MHz respectively are demonstrated). We also show how under certain conditions for quasi-continuous wave sources, the spectral resolution could be further increased by a factor of 100 by direct extraction of phase information from the heterodyned dynamics or by using double time scales within the spectrogram approach

Real-time observation of dissipative soliton formation in nonlinear polarization rotation mode-locked fibre lasers

Formation of coherent structures and patterns from unstable uniform state or noise is a fundamental physical phenomenon that occurs in various areas of science ranging from biology to astrophysics. Understanding of the underlying mechanisms of such processes can both improve our general interdisciplinary knowledge about complex nonlinear systems and lead to new practical engineering techniques. Modern optics with its high precision measurements offers excellent test-beds for studying complex nonlinear dynamics, though capturing transient rapid formation of optical solitons is technically challenging. Here we unveil the build-up of dissipative soliton in mode-locked fibre lasers using dispersive Fourier transform to measure spectral dynamics and employing autocorrelation analysis to investigate temporal evolution. Numerical simulations corroborate experimental observations, and indicate an underlying universality in the pulse formation. Statistical analysis identifies correlations and dependencies during the build-up phase. Our study may open up possibilities for real-time observation of various nonlinear structures in photonic systems

Impact of Tai Chi exercise on multiple fracture-related risk factors in post-menopausal osteopenic women: a pilot pragmatic, randomized trial

Background: Tai Chi (TC) is a mind-body exercise that shows potential as an effective and safe intervention for preventing fall-related fractures in the elderly. Few randomized trials have simultaneously evaluated TC's potential to reduce bone loss and improve fall-predictive balance parameters in osteopenic women. Methods: In a pragmatic randomized trial, 86 post-menopausal osteopenic women, aged 45-70, were recruited from community clinics. Women were assigned to either nine months of TC training plus usual care (UC) vs. UC alone. Primary outcomes were changes between baseline and nine months of bone mineral density (BMD) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry) and serum markers of bone resorption and formation. Secondary outcomes included quality of life. In a subsample (n = 16), quiet standing fall-predictive sway parameters and clinical balance tests were also assessed. Both intent-to-treat and per-protocol analyses were employed. Results: For BMD, no intent-to-treat analyses were statistically significant; however, per protocol analyses (i.e., only including TC participants who completed $\geq$ 75% training requirements) of femoral neck BMD changes were significantly different between TC and UC (+0.04 vs. -0.98%; P = 0.05). Changes in bone formation markers and physical domains of quality of life were also more favorable in per protocol TC vs. UC (P = 0.05). Changes in sway parameters were significantly improved by TC vs. UC (average sway velocity, P = 0.027; anterior-posterior sway range, P = 0.014). Clinical measures of balance and function showed non-significant trends in favor of TC. Conclusions: TC training offered through existing community-based programs is a safe, feasible, and promising intervention for reducing multiple fracture risks. Our results affirm the value of a more definitive, longer-term trial of TC for osteopenic women, adequately powered to detect clinically relevant effects of TC on attenuation of BMD loss and reduction of fall risk in this population

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

A road map for designing and implementing a biological monitoring program

Designing and implementing natural resource monitoring is a challenging endeavor undertaken by many agencies, NGOs, and citizen groups worldwide. Yet many monitoring programs fail to deliver useful information for a variety of administrative (staffing, documentation, and funding) or technical (sampling design and data analysis) reasons. Programs risk failure if they lack a clear motivating problem or question, explicit objectives linked to this problem or question, and a comprehensive conceptual model of the system under study. Designers must consider what “success” looks like from a resource management perspective, how desired outcomes translate to appropriate attributes to monitor, and how they will be measured. All such efforts should be filtered through the question “Why is this important?” Failing to address these considerations will produce a program that fails to deliver the desired information. We addressed these issues through creation of a “road map” for designing and implementing a monitoring program, synthesizing multiple aspects of a monitoring program into a single, overarching framework. The road map emphasizes linkages among core decisions to ensure alignment of all components, from problem framing through technical details of data collection and analysis, to program administration. Following this framework will help avoid common pitfalls, keep projects on track and budgets realistic, and aid in program evaluations. The road map has proved useful for monitoring by individuals and teams, those planning new monitoring, and those reviewing existing monitoring and for staff with a wide range of technical and scientific skills