An Update to Returning Genetic Research Results to Individuals: Perspectives of the Industry Pharmacogenomics Working Group

The ease with which genotyping technologies generate tremendous amounts of data on research participants has been well chronicled, a feat that continues to become both faster and cheaper to perform. In parallel to these advances come additional ethical considerations and debates, one of which centers on providing individual research results and incidental findings back to research participants taking part in genetic research efforts. In 2006 the Industry Pharmacogenomics Working Group (I‐PWG) offered some ‘Points‐to‐Consider’ on this topic within the context of the drug development process from those who are affiliated to pharmaceutical companies. Today many of these points remain applicable to the discussion but will be expanded upon in this updated viewpoint from the I‐PWG. The exploratory nature of pharmacogenomic work in the pharmaceutical industry is discussed to provide context for why these results typically are not best suited for return. Operational challenges unique to this industry which cause barriers to returning this information are also explained.     

Results from the first computerised Italian surveillance of human Salmonella isolates. The Italian SALM-NET Working Group

We report all the first computerised data collected in Italy for the surveillance of Salmonella isolates. Primarily, within the wide framework of the European Community Human Salmonella Surveillance Project (SALM-NET), we report data on the most commonly isolated serotypes in Italy from January 1994 to December 1996. In addition, we report all computerised data historically collected by some Italian regions regarding the period 1980-1993. Total data included in the Italian SALM-NET data base account for 59,336 Salmonella isolates. In the list of the most frequent isolates starting from 1989, S. Enteritidis always ranked first, followed by S. Typhimurium.     

Pesticides of Potential Ecological Concern in Sediment from South Florida Canals: An Ecological Risk Prioritization for Aquatic Arthropods

A two-tier ecological risk assessment was conducted for pesticides monitored in sediment at 36 sampling sites in south Florida freshwater canals from 1990–2002. For tier 1, we identified the chemicals of potential ecological concern (COPECs) as DDT, DDD, DDE, chlordane and endosulfan based on their exceedence of sediment quality standards at 20 sites. For 12 sites with data on the fraction of organic carbon in sediments, whole sediment concentrations of COPECs were converted to pore water concentrations based on equilibrium partitioning. In tier 2, a probabilistic risk assessment compared distributions of pore water exposure concentrations of COPECs with effects distributions of freshwater arthropod response data from laboratory toxicity tests. Arthropod effects distributions included benthic and non-benthic arthropod species for chlordane (n = 9), DDD (n = 12), DDE (n = 5), DDT (n = 48), and endosulfan (n = 26). The overlap of predicted pore water concentrations and arthropod effects distributions was used as a measure of risk. DDE was the most frequently detected COPEC in sediment at the 12 sites. Chlordane was present at only one site. The mean 90th centile concentration for pore water exposure was highest for endosulfan and lowest for DDT. The estimated acute 10th centile concentration for effects was highest for chlordane and lowest for DDD. The probability of pore water exposures of COPECs exceeding the estimated 10th centile concentrations for species sensitivity distributions of arthropod acute toxicity data was between 0 and 1%. The estimated NOEC 10th centile concentration from arthropod chronic toxicity distributions was exceeded by the estimated 90th centile concentration for pore water distributions at three sites. Endosulfan had the highest potential chronic risk at S-178 in the C-111 canal system, based on the probability of pore water exposure concentrations exceeding the arthropod estimated chronic NOEC 10th centile at 41%. The COPEC with the next highest probability of exceeding the chronic NOEC 10th centile was DDD at 17.7% and 19.8% in the Everglades Agricultural Area (at S-2 and S-6). DDT had minimal potential chronic risk. Uncertainties in exposure and effects analysis and risk characterization are discussed.     

A New Design and some Preliminary Results for a Flight Intercept Trap to Sample Forest Canopy Arthropods

With increasing interest in describing the arthropod fauna of rainforest canopies, there is also a need for different trapping techniques which, in combination, will allow a greater proportion of the fauna to be sampled. We describe the design of a flight intercept trap which can be suspended in the rainforest canopy for long periods of time. the flying invertebrate fauna was sampled over 5 months at differing heights in rainforest of northern Queensland using this trap. Invertebrate abundance and higher taxon richness was greatest at the ground level compared to 5 and 10 m above the ground. Similar results were obtained for dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) which were sorted to species. These results contrast with those of other studies using light traps for which insect diversity and abundance was greatest in the rainforest canopy.     

Comparison of pesticide sensitivity by electrochemical test based on acetylcholinesterase biosensor

Based on the change in electrochemical behavior of enzymatic activity induced by pesticide, a novel electrochemical method has been devised for investigation of pesticide sensitivity using acetylcholinesterase (AChE) biosensor. Because of the excellent biocompatibility and good stability of chitosan matrix, it prevented leakage of the AChE from electrode. Multiwall carbon nanotube (MWNT) promoted electron transfer reaction at a lower potential and catalyzed the electro-oxidation of thiocholine, thus amplifying the sensitivity and amperometric response of the biosensor. Four pesticides of carbaryl, malathion, dimethoate and monocrotophos were selected to discuss their inhibition efficiencies to AChE. The inhibition curves were similar to Michealis-Menten and the Michealis-Menten constants (Km) were calculated to be 0.96 microM, 1.78 microM, 1.97 microM and 4.28 microM, respectively. Ninety-five percent reactivation of the inhibited AChE could be regenerated using pralidoxime iodide within 8 min. The proposed electrochemical pesticide sensitivity test exhibited high sensitivity, low cost and simplified procedures, which is a promising new tool for comparison of pesticide sensitivity and for selection of the most efficient enzyme inhibitors.     

Investigations for the development of a biochemical joint function test

The reversible and thus potentially curable, early stage of degenerative joint diseases, so consequential for both the individual and the economy, has so far not been diagnosable objectively. Intraarticular functional tests aim at detecting latent metabolic changes in the joint in order to find out early changes in risked persons. The present animal experiments on osteoarthrosis showed early changes of the glycogen metabolism and the swelling behaviour of the articular cartilage. Therefore, the diagnostic value of intraarticular injections of depot glucose was tested in the form of metabolizable hydroxyethyl starch and the non-metabolizable dextran, which were administered as non-buffered solutions. 35 ml of 0.5% solutions of hydroxyethyl starch or dextran in isotonic saline were injected intraarticularly to unselected patients before knee operations. By means of punctures of the joint 10 min, 1 h, 5 h, and 24 h after the injection, about 3 ml fluid samples were taken for biochemical, biophysical and cytological examinations. The examination produced, for the first time, evidence on the volume and composition of the synovia of osteoarthrosis patients from whom no synovial fluid can be obtained. The analysis of the punctates after loading permits of grouping the patients according to osteoarthrotic changes and various reaction patterns of the synovial marginal tissue with regard to disposition to exudation.     

Arthropods in epiphytes: a diversity component that is not effectively sampled by canopy fogging

Insecticide fogging is often used to document arthropod species richnessin forest canopies, but this technique may not effectively sample invertebratesthat are concealed within a variety of microhabitats. We quantified the effectsof fogging on invertebrates in canopy epiphyte mats of a Costa Rican cloudforest by extracting arthropods from 18 paired pre- and post-fogging samples.Mean abundance and morphospecies richness of living arthropods were respectivelyreduced by 33 and 30% in epiphyte material after fogging, but most organismssurvived the treatment. Relative abundances of major taxa were unaffected byfogging. Herbivores were less abundant after fogging than other trophic groups,and the median body length of non-mite arthropods present in epiphytes wassignificantly smaller after fogging. Examination of seven post-fogging samplesshowed that many arthropods killed by insecticide remained trapped within theepiphyte material. These results provide the first quantitative assessment of aspecific component of arboreal arthropod biodiversity that is missed by thefogging technique.     

Influenza Vaccination Uptake among the Working Age Population of Japan: Results from a National Cross-Sectional Survey

Background

Influenza vaccination rates among Japanese people of working age (20–69 years) is currently suboptimal, and the reasons for this have not been clearly elucidated. This study examined factors associated with vaccination intention among the working age population in Japan during September 2011, one-month prior to influenza vaccination becoming available.

Methodology/Principal Findings

A web-based survey of intention to be vaccinated against influenza in the coming season was undertaken among 3,129 Japanese aged 20 to 69 years. Multinomial logistic regression analysis was used to explore the associations between vaccination intent and other variables. Influenza vaccination intent was associated with having been vaccinated in the previous year (Odds Ratio (OR): 3.81; 95% Confidence Interval (CI): 3.75–3.86), the number of children per household (one compared with zero; OR: 1.37; 95%CI: 1.11–1.65), and household income ($50,000 to <$100,000 compared with $0 to <$50,000; OR: 1.30; 95%CI: 1.07–1.54). Smoking was inversely associated with influenza vaccine uptake (current smokers compared with non-smokers; OR: 0.79; 95%CI: 0.61–0.98). A history of either the survey respondent or a household member having being medically diagnosed with influenza in the previous year was not statistically associated with future influenza vaccination intent.

Conclusions/Significance

Overall, this suggests that intention to be vaccinated among working age Japanese is associated with a past history of influenza vaccination, having children, and the household''s income. As such, consideration of these factors should now form the cornerstone of strategies to encourage increased uptake of vaccination against influenza in future years.     

Transport of Wild-Type and Recombinant Nucleopolyhedroviruses by Scavenging and Predatory Arthropods

Abstract Wild-type and recombinant nucleopolyhedroviruses (NPVs) were compared in their capability to be transported over limited distances by the predator Podisus maculiventris (Say) and scavengers Sarcophaga bullata (Parker) and Acheta domesticus (Linnaeus) in Trichoplusia ni (Hübner) larvae infesting collards in a greenhouse microcosm. Viruses tested were variants of Autographa californica (Speyer) NPV (AcNPV): wild-type virus (AcNPV.WT), AcNPV expressing a scorpion toxin (AcNPV.AaIT), and AcNPV expressing juvenile hormone esterase (AcJHE.SG). Podisus maculiventris transported AcNPV.WT and S. bullata transported AcNPV.WT and AcNPV.AaIT. Prevalence and transport of AcNPV.WT were greater than those of AcNPV.AaIT and AcJHE.SG, regardless of whether the nontarget organism carriers were present or absent. Podisus maculiventris and S. bullata transported recombinant and wild-type NPVs at a rate of up to 62.5 cm/day, and A. domesticus transported wild-type NPV at 125 cm/day. The infected host insects, T. ni, undoubtedly contributed to viral transport in the current research. In every experiment, both the wild-type and recombinant virus spread to some degree in the plots without predators or scavengers. The relative amounts of NPVs that accumulated in soil, as indicated by bioassay mortality percentages, generally exhibited spatial patterns similar to those of T. ni mortality due to NPV on the collards plants. Thus, the predator and scavengers in the current research demonstrated some capacity to transport wild-type as well as recombinant viruses at significant rates in a greenhouse microcosm. Received: 6 December 1999; Accepted: 29 February 2000; Online Publication: 12 May 2000     

Effect of the Canadian Air Force training programme on a submaximal exercise test.

Validation of the submaximal heart rate/oxygen consumption relationship as an index of 'cardiorespiratory fitness' requires the demonstration of systematic alterations in this relationship concomitant with interventions designed to alter physical fitness. To fulfil those criteria a longitudinal training/de-training study was undertaken. Previously sedentary adult subjects undertook the Canadian Airforce 5BX-XBX exercise programme. Submaximal exercise tests were performed before and after training, and following several weeks cessation of training. A regression line of submaximal heart rate on submaximal oxygen consumption was calculated from the data of each submaximal exercise test. Alterations in the regression lines were examined for each subject individually by testing statistically for difference in slope and elevation between any pair of lines. Subjects who undertook the training/de-training study demonstrated significant systematic alterations in the elevation of the regression lines concomitant with periods of training and de-training. The reproducibility of the submaximal heart rate/oxygen consumption relationship was examined in two additional groups of subjects. Group A repeated a submaximal test on 3 or 4 successive days; Group B were tested before and after 16 weeks of normal activity. Subjects in Group A demonstrated non significant, random alterations in the regression lines on repeated testing and subjects in Group B demonstrated random, though on occasion significant, alterations in the regression lines. The elevation of the submaximal heart rate/oxygen consumption relationship is therefore a valid index for detecting sequential changes in 'cardiorespiratory fitness' in individual subjects.     

A study in test reproducibility between laboratories: Report of a Pseudomonas Working Party

The results are reported of a collaborative study in laboratories of 17 tests commonly used for pseudomonads, together with statistical analysis of the results in the form of analyses of variance. The studies involved 59 strains. The following tests showed good or reasonably good consistency between different laboratories: motility if checked by a Craigie tube, growth at 4 C, production of fluorescin, oxidation of glucose and sucrose, gluconate oxidation, hydrolysis of aesculin, arginine and casein, and gelatin hydrolysis by the tube method. The following were less satisfactory: shape, size and arrangement of organismis, growth at 42 C, oxidase, acid from lactose, reduction of nitrate, acetic acid from ethanol, gelatin hydrolysis by the plate method, and the egg yolk reaction. The following showed poor consistency or noticeable difficulties in performing or interpreting results of the test: growth at 37 C, the denitrification test of Stanier, Palleroni and Doudoroff, and hydrolysis of urea. However, with several of the unsatisfactory tests the replicates within a laboratory showed much better reproducibility. This (together with other evidence on the importance of exact control of variables such as temperature, and time of reading, and the occurrence of mutants in some strains) suggests that careful attention to standardization may give much better testing methods. The considerable value of statistical analyses in such work is discussed.