Micrometeoroid and Lunar Secondary Ejecta Flux Measurements: Comparison of Three Acoustic Systems

This report examines the inherent capability of three large-area acoustic sensor systems and their applicability for micrometeoroids (MM) and lunar secondary ejecta (SE) detection and characterization for future lunar exploration activities. Discussion is limited to instruments that can be fabricated and deployed with low resource requirements. Previously deployed impact detection probes typically have instrumented capture areas less than 0.2 square meters. Since the particle flux decreases rapidly with increased particle size, such small-area sensors rarely encounter particles in the size range above 50 microns, and even their sampling the population above 10 microns is typically limited. Characterizing the sparse dust population in the size range above 50 microns requires a very large-area capture instrument. However it is also important that such an instrument simultaneously measures the population of the smaller particles, so as to provide a complete instantaneous snapshot of the population. For lunar or planetary surface studies, the system constraints are significant. The instrument must be as large as possible to sample the population of the largest MM. This is needed to reliably assess the particle impact risks and to develop cost-effective shielding designs for habitats, astronauts, and critical instrument. The instrument should also have very high sensitivity to measure the flux of small and slow SE particles. is the SE environment is currently poorly characterized, and possess a contamination risk to machinery and personnel involved in exploration. Deployment also requires that the instrument add very little additional mass to the spacecraft. Three acoustic systems are being explored for this application

Optical fibers with interferometric path length stability by controlled heating for transmission of optical signals and as components in frequency standards

We present a simple method to stabilize the optical path length of an optical fiber to an accuracy of about 1/100 of the laser wavelength. We study the dynamic response of the path length to modulation of an electrically conductive heater layer of the fiber. The path length is measured against the laser wavelength by use of the Pound-Drever-Hall method; negative feedback is applied via the heater. We apply the method in the context of a cryogenic resonator frequency standard.Comment: Expanded introduction and outlook. 9 pages, 5 figure

Fiber Acoustic Waveguide : A Sensor Candidate

Sensor development plays a key role in the field of nondestructive evaluation and process control. The annual fiber optic sensor market alone is a multimillion dollar business (1). Acoustic waves are about five orders of magnitude slower than optical waves and can also be guided in cladded glass fibers, similar to optical fibers, with low loss and low dispersion (2–7). Fiber acoustic waveguides are believed to be a very attractive and basic component for further sensor development (8). In this paper a brief theoretical description of a weakly guiding acoustic fiber (7) is given. The material selection criteria for the core and the cladding of the fiber guide, the properties of single-mode operation, and some sensing mechanisms for temperature and pressure variations are discussed. The acoustic waveguide with a liquid core is also considered

NCoR Repression of LXRs Restricts Macrophage Biosynthesis of Insulin-Sensitizing Omega 3 Fatty Acids

SummaryMacrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies

Outcome based subgroup analysis: a neglected concern

A subgroup of clinical trial subjects identified by baseline characteristics is a proper subgroup while a subgroup determined by post randomization events or measures is an improper subgroup. Both types of subgroups are often analyzed in clinical trial papers. Yet, the extensive scrutiny of subgroup analyses has almost exclusively attended to the former. The analysis of improper subgroups thereby not only flourishes in numerous disguised ways but also does so without a corresponding awareness of its pitfalls. Comparisons of the grade of angina in a heart disease trial, for example, usually include only the survivors. This paper highlights some of the distinct ways in which outcome based subgroup analysis occurs, describes the hazards associated with it, and proposes a simple alternative approach to counter its analytic bias. Data from six published trials show that outcome based subgroup analysis, like proper subgroup analysis, may be performed in a post-hoc fashion, overdone, selectively reported, and over interpreted. Six hypothetical trial scenarios illustrate the forms of hidden bias related to it. That bias can, however, be addressed by assigning clinically appropriate scores to the usually excluded subjects and performing an analysis that includes all the randomized subjects. A greater level of awareness about the practice and pitfalls of outcome based subgroup analysis is needed. When required, such an analysis should maintain the integrity of randomization. This issue needs greater practical and methodologic attention than has been accorded to it thus far

Estimating time-to-onset of adverse drug reactions from spontaneous reporting databases.

International audienceBACKGROUND: Analyzing time-to-onset of adverse drug reactions from treatment exposure contributes to meeting pharmacovigilance objectives, i.e. identification and prevention. Post-marketing data are available from reporting systems. Times-to-onset from such databases are right-truncated because some patients who were exposed to the drug and who will eventually develop the adverse drug reaction may do it after the time of analysis and thus are not included in the data. Acknowledgment of the developments adapted to right-truncated data is not widespread and these methods have never been used in pharmacovigilance. We assess the use of appropriate methods as well as the consequences of not taking right truncation into account (naïve approach) on parametric maximum likelihood estimation of time-to-onset distribution. METHODS: Both approaches, naïve or taking right truncation into account, were compared with a simulation study. We used twelve scenarios for the exponential distribution and twenty-four for the Weibull and log-logistic distributions. These scenarios are defined by a set of parameters: the parameters of the time-to-onset distribution, the probability of this distribution falling within an observable values interval and the sample size. An application to reported lymphoma after anti TNF-¿ treatment from the French pharmacovigilance is presented. RESULTS: The simulation study shows that the bias and the mean squared error might in some instances be unacceptably large when right truncation is not considered while the truncation-based estimator shows always better and often satisfactory performances and the gap may be large. For the real dataset, the estimated expected time-to-onset leads to a minimum difference of 58 weeks between both approaches, which is not negligible. This difference is obtained for the Weibull model, under which the estimated probability of this distribution falling within an observable values interval is not far from 1. CONCLUSIONS: It is necessary to take right truncation into account for estimating time-to-onset of adverse drug reactions from spontaneous reporting databases

Implementing microbicides in low-income countries.

The magnitude of the global human immunodeficiency virus (HIV) epidemic is determined by women from lower income countries, specifically sub-Saharan Africa. Microbicides offer women who are unable to negotiate safe sex practices a self-initiated HIV prevention method. Of note, is its potential to yield significant public health benefits even with relatively conservative efficacy, coverage and user adherence estimates, making microbicides an effective intervention to invest scarce healthcare resources. Existing healthcare delivery systems provide an excellent opportunity to identify women at highest risk for infection and to also provide an access point to initiate microbicide use. Innovative quality improvement approaches, which strengthen existing sexual reproductive health services and include HIV testing, and linkages to care and treatment services, provide an opportunity to lay the foundations for wide-scale provision of microbicides. The potential to enhance health outcomes in women and infants and potentially affect rates of new HIV infection may soon be realised

Targeting targeted agents: open issues for clinical trial design

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources

Variables with time-varying effects and the Cox model: Some statistical concepts illustrated with a prognostic factor study in breast cancer

International audienceBACKGROUND: The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups. METHODS: We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered. RESULTS: Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups. CONCLUSIONS: Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise

Characterization of cladded glass fibers using acoustic microscopy

Spatial distribution profiles of leaky surface acoustic wave velocity V(LSAW) and attenuation across the diameters of cladded glass fibers are presented. The profiles are obtained by using a novel V(x,z) analysis with a reflection scanning acoustic microscope operated at 775 MHz, and are compared with optical refractive index profiles. Optical fibers with different dopants and dopant concentrations have been investigated. The role of acoustic property profiles in the design of optical and acoustic fibers is outlined