Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far?

This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench. [Authors]

Synthesis of Nondestructive Testing Technologies for Geomaterial Applications, May 2005

Current monitoring techniques for determination of compaction of earthwork and asphalt generally involve destructive testing of the materials following placement. Advances in sensor technologies show significant promise for obtaining necessary information through nondestructive and remote techniques. To develop a better understanding of suitable and potential technologies, this study was undertaken to conduct a synthesis review of nondestructive testing technologies and perform preliminary evaluations of selected technologies to better understand their application to testing of geomaterials (soil fill, aggregate base, asphalt, etc.). This research resulted in a synthesis of potential technologies for compaction monitoring with a strong emphasis on moisture sensing. Techniques were reviewed and selectively evaluated for their potential to improve field quality control operations. Activities included an extensive review of commercially available moisture sensors, literature review, and evaluation of selected technologies. The technologies investigated in this study were dielectric, nuclear, near infrared spectroscopy, seismic, electromagnetic induction, and thermal. The primary disadvantage of all the methods is the small sample volume measured. In addition, all the methods possessed some sensitivity to non-moisture factors that affected the accuracy of the results. As the measurement volume increases, local variances are averaged out providing better accuracy. Most dielectric methods with the exception of ground penetrating radar have a very small measurement volume and are highly sensitive to variations in density, porosity, etc.

Splitting statistical potentials into meaningful scoring functions: testing the prediction of near-native structures from decoy conformations

Background: Recent advances on high-throughput technologies have produced a vast amount of protein sequences, while the number of high-resolution structures has seen a limited increase. This has impelled the production of many strategies to built protein structures from its sequence, generating a considerable amount of alternative models. The selection of the closest model to the native conformation has thus become crucial for structure prediction. Several methods have been developed to score protein models by energies, knowledge-based potentials and combination of both.Results: Here, we present and demonstrate a theory to split the knowledge-based potentials in scoring terms biologically meaningful and to combine them in new scores to predict near-native structures. Our strategy allows circumventing the problem of defining the reference state. In this approach we give the proof for a simple and linear application that can be further improved by optimizing the combination of Zscores. Using the simplest composite score () we obtained predictions similar to state-of-the-art methods. Besides, our approach has the advantage of identifying the most relevant terms involved in the stability of the protein structure. Finally, we also use the composite Zscores to assess the conformation of models and to detect local errors.Conclusion: We have introduced a method to split knowledge-based potentials and to solve the problem of defining a reference state. The new scores have detected near-native structures as accurately as state-of-art methods and have been successful to identify wrongly modeled regions of many near-native conformations.

Feeding and the Equilibrium Feeder Animal Price-Weight Schedule, June 2005

The feeder animal price is a derivative in the sense that its value depends upon the price of animals for the consumption market. It also depends upon the biological growth technology and feed costs. Daily maintenance costs are of particular interest to the husbander because they can be avoided through accelerated feeding. In this paper, the optimal feeding path under equilibrium feeder animal prices is established. This analysis is used to gain a better understanding of feeding decisions, regulation in feedstuff markets, and the consequences of genetic innovations. It is shown that days on feed can increase or decrease with a genetic innovation or other improvement in feed conversion efficiency. The structure of comparative prices for feeder animals at different weights, the early slaughter decision, and equilibrium in feeder animal markets are also developed. Feeder animal prices can increase over a weight interval if biological feed efficiency parameters are low over the interval.

A multicenter study to validate the reproducibility of MSI testing with a panel of 5 quasimonomorphic mononucleotide repeats.

Microsatellite instability (MSI) testing in clinics is becoming increasingly widespread; therefore, there is an urgent need for methodology standardization and the availability of quality control. This study is aimed to assess the interlaboratory reproducibility of MSI testing in archive samples by using a panel of 5 recently introduced, mononucleotide repeats (MNR). The quality control involved 8 European institutions. Participants were supplied with DNA extracted from 15 archive colon carcinoma samples and from the corresponding normal tissues. Every group was asked to assess the MSI status of the samples by using the BAT25, BAT26, NR21, NR24, and NR27 mononucleotide markers. Four institutions repeated the analysis using the NCI reference panel to confirm the results obtained with the MNR markers. The overall concordance among institutions for MSI analyses at single locus level was 97.7% when using the MNR panel and 95.0% with the NCI one. The laboratories obtained a full agreement in scoring the MSI status of each patient sample, both using the mononucleotide and the NCI marker sets. With the NCI marker set, however, concordance was lowered to 85.7% when considering the MSI-Low phenotype. Concordance between the 2 panels in scoring the MSI status of each sample was complete if no discrimination was made between MSI-Stable and MSI-L, whereas it dropped to 76.7% if MSI-L was considered. In conclusion, the use of the MNR panel seems to be a robust approach that yields a very high level of reproducibility. The results obtained with the 5 MNR are diagnostically consistent with those obtained by the use of the NCI markers, except for the MSI-Low phenotype.

Determination and Evaluation of Alternative Methods for Managing and Controlling Highway-Related Dust Phase II—Demonstration Project, June 2005

The State of Iowa currently has approximately 69,000 miles of unpaved secondary roads. Due to the low traffic count on these unpaved o nts as ng e two dust ed d roads, paving with asphalt or Portland cement concrete is not economical. Therefore to reduce dust production, the use of dust suppressants has been utilized for decades. This study was conducted to evaluate the effectiveness of several widely used dust suppressants through quantitative field testing on two of Iowa’s most widely used secondary road surface treatments: crushed limestone rock and alluvial sand/gravel. These commercially available dust suppressants included: lignin sulfonate, calcium chloride, and soybean oil soapstock. These suppressants were applied to 1000 ft test sections on four unpaved roads in Story County, Iowa. Tduplicate field conditions, the suppressants were applied as a surface spray once in early June and again in late August or early September. The four unpaved roads included two with crushed limestone rock and two with alluvial sand/gravel surface treatmewell as high and low traffic counts. The effectiveness of the dust suppressants was evaluated by comparing the dust produced on treated and untreated test sections. Dust collection was scheduled for 1, 2, 4, 6, and 8 weeks after each application, for a total testiperiod of 16 weeks. Results of a cost analysis between annual dust suppressant application and biennial aggregate replacement indicated that the cost of the dust suppressant, its transportation, and application were relatively high when compared to that of thaggregate types. Therefore, the biennial aggregate replacement is considered more economical than annual dust suppressant application, although the application of annual dust suppressant reduced the cost of road maintenance by 75 %. Results of thecollection indicated that the lignin sulfonate suppressant outperformed calcium chloride and soybean oil soapstock on all four unpavroads, the effect of the suppressants on the alluvial sand/gravel surface treatment was less than that on the crushed limestone rock, the residual effects of all the products seem reasonably well after blading, and the combination of alluvial sand/gravel surface treatment anhigh traffic count caused dust reduction to decrease dramatically.

Correlations between imatinib pharmacokinetics, pharmacodynamics, adherence, and clinical response in advanced metastatic gastrointestinal stromal tumor (GIST): An emerging role for drug blood level testing?

Imatinib is the standard of care for patients with advanced metastatic gastrointestinal stromal tumors (GIST), and is also approved for adjuvant treatment in patients at substantial risk of relapse. Studies have shown that maximizing benefit from imatinib depends on long-term administration at recommended doses. Pharmacokinetic (PK) and pharmacodynamic factors, adherence, and drug-drug interactions can affect exposure to imatinib and impact clinical outcomes. This article reviews the relevance of these factors to imatinib's clinical activity and response in the context of what has been demonstrated in chronic myelogenous leukemia (CML), and in light of new data correlating imatinib exposure to response in patients with GIST. Because of the wide inter-patient variability in drug exposure with imatinib in both CML and GIST, blood level testing (BLT) may play a role in investigating instances of suboptimal response, unusually severe toxicities, drug-drug interactions, and suspected non-adherence. Published clinical data in CML and in GIST were considered, including data from a PK substudy of the B2222 trial correlating imatinib blood levels with clinical responses in patients with GIST. Imatinib trough plasma levels <1100ng/mL were associated with lower rates of objective response and faster development of progressive disease in patients with GIST. These findings have been supported by other analyses correlating free imatinib (unbound) levels with response. These results suggest a future application for imatinib BLT in predicting and optimizing therapeutic response. Nevertheless, early estimates of threshold imatinib blood levels must be confirmed prospectively in future studies and elaborated for different patient subgroups.

Pédiatrie. 3. Le score de McIsaac: une aide à l'indication des tests de diagnostic rapide dans tes angines à streptocoques A [Pediatrics. Using the McIsaac score for the indication of rapid diagnostic testing in children with streptococcal pharyngitis].

The McIsaac scoring system is a tool designed to predict the probability of streptococcal pharyngitis in children aged 3 to 17 years with a sore throat. Although it does not allow the physician to make the diagnosis of streptococcal pharyngitis, it enables to identify those children with a sore throat in whom rapid antigen detection tests have a good predictive value.

Testing for local adaptation in brown trout using reciprocal transplants.

ABSTRACT: BACKGROUND: Local adaptation can drive the divergence of populations but identification of the traits under selection remains a major challenge in evolutionary biology. Reciprocal transplant experiments are ideal tests of local adaptation, yet rarely used for higher vertebrates because of the mobility and potential invasiveness of non-native organisms. Here, we reciprocally transplanted 2500 brown trout (Salmo trutta) embryos from five populations to investigate local adaptation in early life history traits. Embryos were bred in a full-factorial design and raised in natural riverbeds until emergence. Customized egg capsules were used to simulate the natural redd environment and allowed tracking the fate of every individual until retrieval. We predicted that 1) within sites, native populations would outperform non-natives, and 2) across sites, populations would show higher performance at 'home' compared to 'away' sites. RESULTS: There was no evidence for local adaptation but we found large differences in survival and hatching rates between sites, indicative of considerable variation in habitat quality. Survival was generally high across all populations (55% +/- 3%), but ranged from 4% to 89% between sites. Average hatching rate was 25% +/- 3% across populations ranging from 0% to 62% between sites. CONCLUSION: This study provides rare empirical data on variation in early life history traits in a population network of a salmonid, and large-scale breeding and transplantation experiments like ours provide powerful tests for local adaptation. Despite the recently reported genetic and morphological differences between the populations in our study area, local adaptation at the embryo level is small, non-existent, or confined to ecological conditions that our experiment could not capture.

Gonadotrophin replacement for induction of fertility in hypogonadal men.

Congenital hypogonadotrophic hypogonadism (CHH) is a rare form of infertility caused by deficient secretion or action of gonadotrophin-releasing hormone. There is no consensus regarding the optimal approach to fertility treatment in CHH men. In most cases, appropriate hormonal treatment with human chorionic gonadotrophin with or without follicle stimulating hormone will induce testicular development, spermatogenesis and fertility. Recent studies have examined sequential treatment with FSH pre-treatment to optimize fertility outcomes in severely affected CHH patients. This paper reviews historical and recent literature to summarize the current evidence on therapeutic approaches for CHH men seeking fertility.

Tigecycline in combination with other antimicrobials: a review of in vitro, animal and case report studies.

Tigecycline has been investigated in combination with other antibacterials against a wide range of susceptible and multiresistant Gram-positive and Gram-negative bacteria. Combinations have been analysed in vitro, in animal models and in human case reports. In vitro, tigecycline combined with other antimicrobials produces primarily an indifferent response (neither synergy nor antagonism). Nevertheless, synergy occurred when tigecycline was combined with rifampicin against 64-100% of Enterococcus spp., Streptococcus pneumoniae, Enterobacter spp. and Brucella melitensis isolates. Combinations of tigecycline with amikacin also showed synergy for 40-100% of Enterobacter spp., Klebsiella pneumoniae, Proteus spp. and Stenotrophomonas maltophilia isolates. Moreover, bactericidal synergisms occurred with tigecycline plus amikacin against problematic Acinetobacter baumannii and Proteus vulgaris, and with colistin against K. pneumoniae. Data from animal experiments and case reports, although limited, displayed consistent beneficial activity of tigecycline in combination with other antibacterials against multiresistant organisms, including vancomycin against penicillin-resistant S. pneumoniae in experimental meningitis, gentamicin against Pseudomonas aeruginosa in experimental pneumonia, daptomycin against Enterococcus faecium endocarditis, and colistin against K. pneumoniae bacteraemia and P. aeruginosa osteomyelitis. Antagonism was extremely rare in vitro and was not reported in vivo. Thus, tigecycline may be combined with a second antimicrobial as part of a combination regimen.

Opportunistic testing for urogenital infection with Chlamydia trachomatis in south-western Switzerland, 2012 : a feasibility study

The feasibility of opportunistic screening of urogenital infections with Chlamydia trachomatis was assessed in a cross-sectional study in 2012, in two cantons of south-western Switzerland: Vaud and Valais. Sexually active persons younger than 30 years, not tested for C. trachomatis in the last three months, were invited for free C. trachomatis testing by PCR in urine or self-applied vaginal swabs. Of 2,461 consenting participants, 1,899 (77%) were women and all but six (0.3%) submitted a sample. Forty-seven per cent of female and 25% of male participants were younger than 20 years. Overall, 134 (5.5%) of 2,455 tested participants had a positive result and were followed up. Seven per cent of all candidates for screening were not invited, 10% of invited candidates were not eligible, 15% of the eligible candidates declined participation, 5% of tested participants testing positive were not treated, 29% of those treated were not retested after six months and 9% of those retested were positive for C. trachomatis. Opportunistic C. trachomatis testing proved technically feasible and acceptable, at least if free of charge. Men and peripheral rural regions were more difficult to reach. Efforts to increase testing and decrease dropout at all stages of the screening procedure are necessary.

Biosecurity and Infectious Animal Disease, November 2005

The spatial dimension of agricultural production is important when a communicable disease enters a region. This paper considers two sorts of biosecurity risk that producers can seek to protect against. One concerns the risk of spread: that neighboring producers do not take due care in protecting against being infected by a disease already in the region. In this case, producer efforts substitute with those of near neighbors. For representative spatial production structures, we characterize Nash equilibrium protection levels and show how spatial production structure matters. The other sort of risk concerns entry: that producers do not take due care in preventing the disease from entering the region. In this case, producer heterogeneity has subtle effects on welfare loss due to strategic behavior. Efforts by producers complement, suggesting that interfarm communication will help to redress the problem.