In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosis in sputum specimens: meta-analysis and meta-regression

BACKGROUND: More than 200 studies related to nucleic acid amplification (NAA) tests to detect Mycobacterium tuberculosis directly from clinical specimens have appeared in the world literature since this technology was first introduced. NAA tests come as either commercial kits or as tests designed by the reporting investigators themselves (in-house tests). In-house tests vary widely in their accuracy, and factors that contribute to heterogeneity in test accuracy are not well characterized. Here, we used meta-analytical methods, including meta-regression, to identify factors related to study design and assay protocols that affect test accuracy in order to identify those factors associated with high estimates of accuracy. RESULTS: By searching multiple databases and sources, we identified 2520 potentially relevant citations, and analyzed 84 separate studies from 65 publications that dealt with in-house NAA tests to detect M. tuberculosis in sputum samples. Sources of heterogeneity in test accuracy estimates were determined by subgroup and meta-regression analyses. Among 84 studies analyzed, the sensitivity and specificity estimates varied widely; sensitivity varied from 9.4% to 100%, and specificity estimates ranged from 5.6% to 100%. In the meta-regression analysis, the use of IS6110 as a target, and the use of nested PCR methods appeared to be significantly associated with higher diagnostic accuracy. CONCLUSION: Estimates of accuracy of in-house NAA tests for tuberculosis are highly heterogeneous. The use of IS6110 as an amplification target, and the use of nested PCR methods appeared to be associated with higher diagnostic accuracy. However, the substantial heterogeneity in both sensitivity and specificity of the in-house NAA tests rendered clinically useful estimates of test accuracy difficult. Future development of NAA-based tests to detect M. tuberculosis from sputum specimens should take into consideration these findings in improving accuracy of in-house NAA tests

Proposal for a low cost close air support aircraft for the year 2000: The Raptor

The Raptor is a proposed low cost Close Air Support (CAS) aircraft for the U.S. Military. The Raptor incorporates a 'cranked arrow' wing planform, and uses canards instead of a traditional horizontal tail. The Raptor is designed to be capable of responsive delivery of effective ordnance in close proximity to friendly ground forces during the day, night, and 'under the weather' conditions. Details are presented of the Raptor's mission, configuration, performance, stability and control, ground support, manufacturing, and overall cost to permit engineering evaluation of the proposed design. A description of the design process and analysis methods used is also provided

Characteristics of Some Fruiting Plant Species in Northwest Arkansas, and the Avian Assemblages that Feed on Them

Fruits continue to be recognized as an important food source for birds in temperate areas, particularly during the fall migration period. More than 20 species of plants producing fleshy fruits are found in the Arkansas Ozarks. However, only a few of these appear to be important resources for birds during the fall migration period (August - October). Among those are sassafras (Sassafras albidum), gray-backed grape (Vitis cinerea), black cherry (Prunus serotina), hercules club (Araliaspinosa) and pokeweed (Phytolacca americana). Over the past 4 years, we have documented the physical and nutritional characteristics of those fruits and taken observational data on the assemblages of birds eating them. It appears that avian species assemblages feeding on fruits are partially determined by the physical and nutritional contents of those fruits. Sassafras is extremely lipid-rich and higher in caloric content than the other species of fruits. It appears to be eaten almost exclusively by larger birds, perhaps be due to the large size of its fruits, which may exceed gape width of many smaller bird species. Prunus and Vitis are also eaten by a large number of avian species. Phytolacca was eaten only by a small number of primarily resident bird species and often persisted into the winter. Reasons for this pattern are not clear, as it was relatively similar to the other fruits inmost characteristics. Aralia was seen being eaten by only a few species of birds but is less common than the other species, and its small fruits may not be as attractive as those of the other species. Compared to other places in the east, there appear to be a relatively low number of migratory frugivorous birds in northwestern Arkansas. Overall, there were very few species noted at any fruiting plants, and a large proportion of the total assemblage of birds was comprised of resident species

Identification of Trypanocidal Activity for Known Clinical Compounds Using a New <i>Trypanosoma cruzi</i> Hit-Discovery Screening Cascade

<div><p>Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-<i>Trypanosoma cruzi</i> activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.</p></div

The impact of streetlights on an aquatic invasive species: artificial light at night alters signal crayfish behaviour

Artificial light at night (ALAN) can significantly alter the behaviour, communication and orientation of animals, and will potentially interact with other stressors to affect biodiversity. Invasive, non-native species are one of the largest threats to freshwater biodiversity; however, the impact of ALAN on such species is unknown. This study assessed the effects of ALAN at ecologically relevant levels on the behaviour of a globally widespread invasive species, the signal crayfish (Pacifastacus leniusculus). In experimental aquaria, crayfish were exposed to periods of daylight, control (<0.1 lx) and street-lit nights to test two hypotheses: (1) signal crayfish under natural conditions are nocturnal animals, spending more time in shelter during the day, whilst active and interacting during the night, and (2) ALAN reduces crayfish activity and intraspecific interactions, whilst increasing their propensity to use shelter. Our results confirm that signal crayfish are largely nocturnal, showing peak activity and interaction levels during control nights, whilst taking refuge during daylight hours. When exposed to short-term simulated light pollution from a streetlight at night however, activity and interactions with conspecifics were significantly reduced compared to control nights, whilst time spent in shelters increased. By altering crayfish behaviour, ALAN may change the ecosystem impacts of invasive crayfish in the wild. This study is the first to show an impact of ALAN on the behaviour of an invasive, non-native species, and provides information for the management of invasive crayfish in areas where ALAN is prevalent

Methicillin-resistant Staphylococcus aureus, Western Australia

Endemic MRSA persists in Western Australia despite control measures

Resistant starch wheat increases PYY and decreases GIP but has no effect on self-reported perceptions of satiety

Dietary fiber has numerous health benefits, such as increasing satiety, and is regularly included in healthy dietary recommendations. However, different types and sources of fiber vary in their chemical properties and biological effects. This double-blind, randomized, placebo-controlled, crossover study investigated the effects of resistant starch type 2 (RS2) from wheat on self-reported perceptions of satiety and associated gut hormones in 30 healthy adults ages 40-65 years of age. Participants consumed rolls made using either RS2-enriched wheat flour or a wild-type flour for one week before a test day during which they ate a mixed meal containing the same roll type. Both self-reported perceptions of satiety and plasma concentrations of gut hormones were measured following the meal to assess whether the RS2-enriched wheat enhanced satiety and suppressed hunger for a longer period than the control wheat. Exploratory analysis indicated that fasting and peak concentration of peptide YY3-36 (PYY3-36; qfast&nbsp;=&nbsp;0.02, qpeak&nbsp;=&nbsp;0.02) increased, while peak concentration and iAUC of glucose-dependent insulinotropic peptide (GIP; qpeak &lt; 0.001, qiAUC &lt; 0.001) decreased after ingesting RS2-enriched wheat. However, self-reported perceptions of hunger or fullness using visual analog scales (VAS) did not differ following the test meal

An Evaluation of the Diagnostic Accuracy of the Grade of Preoperative Biopsy Compared to Surgical Excision in Chondrosarcoma of the Long Bones

Chondrosarcoma is the second most common primary malignant bone tumour. Distinguishing between grades is not necessarily straightforward and may alter the disease management. We evaluated the correlation between histological grading of the preoperative image-guided needle biopsy and the resection specimen of 78 consecutive cases of chondrosarcoma of the femur, humerus, and tibia. In 11 instances, there was a discrepancy in histological grade between the biopsy and surgical specimen. Therefore, there was an 85.9% (67/78) accuracy rate for pre-operative histological grading of chondrosarcoma, based on needle biopsy. However, the accuracy of the diagnostic biopsy to distinguish low-grade from high-grade chondrosarcoma was 93.6% (73/78). We conclude that accurate image-guided biopsy is a very useful adjunct in determining histological grade of chondrosarcoma and the subsequent treatment plan. At present, a multidisciplinary approach, comprising experienced orthopaedic surgeons, radiologists, and pathologists, offers the most reliable means of accurately diagnosing and grading of chondrosarcoma of long bones

On the Normalization of the Neutrino-Deuteron Cross Section

As is well-known, comparison of the solar neutrino fluxes measured in SuperKamiokande (SK) by $\nu + e^- \to \nu + e^-$ and in the Sudbury Neutrino Observatory (SNO) by $\nu_e + d \to e^- + p + p$ can provide a ``smoking gun'' signature for neutrino oscillations as the solution to the solar neutrino puzzle. This occurs because SK has some sensitivity to all active neutrino flavors whereas SNO can isolate electron neutrinos. This comparison depends crucially on the normalization and uncertainty of the theoretical charged-current neutrino-deuteron cross section. We address a number of effects which are significant enough to change the interpretation of the SK--SNO comparison.Comment: 4 pages, 1 figure, submitted to PR