Using wildlife activity and antibiotic resistance analysis to model bacterial water quality in coastal ponds

Models that help predict fecal coliform bacteria (FCB) levels in environmental waters can be important tools for resource managers. In this study, we used animal activity along with antibiotic resistance analysis (ARA), land cover, and other variables to build models that predict bacteria levels in coastal ponds that discharge into an estuary. Photographic wildlife monitoring was used to estimate terrestrial and aquatic wildlife activity prior to sampling. Increased duck activity was an important predictor of increased FCB in coastal ponds. Terrestrial animals like deer and raccoon, although abundant, were not significant in our model. Various land cover types, rainfall, tide, solar irradiation, air temperature, and season parameters, in combination with duck activity, were significant predictors of increased FCB. It appears that tidal ponds allow for settling of bacteria under most conditions. We propose that these models can be used to test different development styles and wildlife management techniques to reduce bacterial loading into downstream shellfish harvesting and contact recreation areas.

Rapid detection of white spot syndrome virus (WSSV) of Penaeus monodon by latex agglutination test using monoclonal antibodies

Latex beads were sensitized with monoclonal antibodies (MAb) rose against VP28 of WSSV. The optimum concentration of MAb required to sensitize the latex beads was 125 µg/ml. The sensitized latex beads were used to detect WSSV from PCR-positive stomach tissue homogenates obtained from infected shrimp. Stomach tissue homogenates from WSSV-infected shrimp agglutinated the sensitized latex beads within 10 minutes, while uninfected samples did not produce any agglutination, although non-specific agglutinations were observed in some samples. The analytical sensitivity, analytical specificity, diagnostic sensitivity and diagnostic specificity of the (LAT) agglutination test were assessed. The analytical sensitivity of the test was 40 ng of purified WSSV (2 µg/ml). The sensitized latex beads did not agglutinate with normal shrimp tissue or MBV-infected tissue homogenate. The test has a diagnostic sensitivity of 70 and 45%, respectively, compared to single-step and nested PCR. The diagnostic specificity of the test was 82%. This test is a simple and rapid on-farm test which can be used to corroborate clinical signs for the detection of WSSV in grow-out ponds.

Antibiotic resistance of Staphylococcus aureus strains isolated from fish processing factory workers

One hundred and twenty two strains of Staphylococcus aureus isolated from throats and palms of 39 workers from 6 fish processing factories situated in and around Cochin were tested for their sensitivity to nine commonly used antibiotics-ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin, penicillin, polymyxin-B, streptomycin and tetracycline. Highest percentage of resistance was observed towards ampicillin followed by penicillin i.e. 64.75% and 59.84%. Resistance towards other antibiotics like tetracycline, polymyxin-B, erythromycin, kanamycin, neomycin, chloramphenicol and streptomycin were shown by 22.95, 16.39, 7.38, 5.74, 3.28 and 1.64% of the isolates respectively.

Fiber Bragg grating hydrophone with high sensitivity

A fiber Bragg grating (FBG) hydrophone with high sensitivity was demonstrated. This hydrophone used a rubber diaphragm and a copper hard core as the sensing element. To compensate the hydrostatic pressure, a capillary tube was fixed at the end of the hydrophone. Theoretical analysis of the acoustic pressure sensitivity was given in this letter. Experiments were carried out to test the frequency response of the hydrophone. The result shows that when the Young's modulus of the diaphragm is higher, a flatter frequency response will be obtained.

Test experiments of gamma-ray linear polarization using a Clover detector

We have investigated the performance of a EXOGAM-Segmented-Clover with 16 segments as a Compton polarimeter to measure the linear polarization of gamma rays. The polarization sensitivity of the Clover detector has been measured at the energy of 1332keV through the coincidence measurements of cascade gamma-rays from Co-60. Experimental values were in good accord with our expectation.We have investigated the performance of a EXOGAM-Segmented-Clover with 16 segments as a Compton polarimeter to measure the linear polarization of gamma rays. The polarization sensitivity of the Clover detector has been measured at the energy of 1332keV through the coincidence measurements of cascade gamma-rays from Co-60. Experimental values were in good accord with our expectation.

Application of Neomysis awatschensis as a standard marine toxicity test organism in China

The small mysid crustacean Neomysis awatschensis was collected in the west coast of Jiaozhou Bay, Qingdao, China in 1992 and acclimated and cultured in laboratory conditions since then. Standard acute toxicity tests using 4-6 d juvenile mysids of this species were conducted and the results were compared with Mysidopsis bahia, a standard toxicity test organism used in the US in terms of their sensitivities to reference toxins, as well as their taxonomy, morphology and geographic distributions. Because of its wide distribution along the Chinese coast, similar sensitivity to pollutants as M. bahia, short life history, small size and the case of handling, this study intended to use N. awatschensis as one of the standard marine organisms for toxicity testing in China. The species were applied to acute toxicity evaluations of drilling fluid and its additives I organotin TPT and toxic algae, and to chronic ( life cycle) toxicity assays of organotin TPT and a toxic dinofalgellate Alexandrium tamarense, respectively. Using N, awatschensis as a standard toxicity testing organism in marine pollution assessment in China is suggested.

The Quick Mild Cognitive Impairment (Qmci) screen: developing a new screening test for mild cognitive impairment and dementia

Introduction: Identifying mild cognitive impairment (MCI) is challenging. Few short instruments have sufficient sensitivity and specificity for use in busy clinical practice. This thesis explores the development, psychometric evaluation and validation of a new short (3–5 min) cognitive screening instrument, designed to screen for MCI and early dementia, called the Quick Mild Cognitive Impairment (Q

Robust test method for time-course microarray experiments.

BACKGROUND: In a time-course microarray experiment, the expression level for each gene is observed across a number of time-points in order to characterize the temporal trajectories of the gene-expression profiles. For many of these experiments, the scientific aim is the identification of genes for which the trajectories depend on an experimental or phenotypic factor. There is an extensive recent body of literature on statistical methodology for addressing this analytical problem. Most of the existing methods are based on estimating the time-course trajectories using parametric or non-parametric mean regression methods. The sensitivity of these regression methods to outliers, an issue that is well documented in the statistical literature, should be of concern when analyzing microarray data. RESULTS: In this paper, we propose a robust testing method for identifying genes whose expression time profiles depend on a factor. Furthermore, we propose a multiple testing procedure to adjust for multiplicity. CONCLUSIONS: Through an extensive simulation study, we will illustrate the performance of our method. Finally, we will report the results from applying our method to a case study and discussing potential extensions.

New business models for antibiotic innovation.

The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards.

CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.

The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to 'band-pass' response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.

Tillin, H. & Tyler-Walters, H., 2014. Assessing the sensitivity of subtidal sedimentary habitats to pressures associated with marine activities. Phase 2 Report – Literature review and sensitivity assessments for ecological groups for circalittoral and offshore Level 5 biotopes. JNCC Report No. 512B, 260 pp.

Human activities within the marine environment give rise to a number of pressures on seabed habitats. Improved understanding of the sensitivity of subtidal sedimentary habitats is required to underpin the management advice provided for Marine Protected Areas, as well as supporting other UK marine monitoring and assessment work. The sensitivity of marine sedimentary habitats to a range of pressures induced by human activities has previously been systematically assessed using approaches based on expert judgement for Defra Project MB0102 (Tillin et al. 2010). This previous work assessed sensitivity at the level of the broadscale habitat and therefore the scores were typically expressed as a range due to underlying variation in the sensitivity of the constituent biotopes. The objective of this project was to reduce the uncertainty around identifying the sensitivity of selected subtidal sedimentary habitats by assessing sensitivity, at a finer scale and incorporating information on the biological assemblage, for 33 Level 5 circalittoral and offshore biotopes taken from the Marine Habitat Classification of Britain and Ireland (Connor et al. 2004). Two Level 6 sub-biotopes were also included in this project as these contain distinctive characterising species that differentiate them from the Level 5 parent biotope. Littoral, infralittoral, reduced and variable salinity sedimentary habitats were excluded from this project as the scope was set for assessment of circalittoral and offshore sedimentary communities. This project consisted of three Phases. • Phase 1 - define ecological groups based on similarities in the sensitivity of characterising species from the Level 5 and two Level 6 biotopes described above. • Phase 2 - produce a literature review of information on the resilience and resistance of characterising species of the ecological groups to pressures associated with activities in the marine environment. • Phase 3 - to produce sensitivity assessment ‘proformas’ based on the findings of Phase 2 for each ecological group. This report outlines results of Phase 2. The Tillin et al., (2010) sensitivity assessment methodology was modified to use the best available scientific evidence that could be collated within the project timescale. An extensive literature review was compiled, for peer reviewed and grey literature, to examine current understanding about the effects of pressures from human activities on circalittoral and offshore sedimentary communities in UK continental shelf waters, together with information on factors that contribute to resilience (recovery) of marine species. This review formed the basis of an assessment of the sensitivity of the 16 ecological groups identified in Phase 1 of the project (Tillin & Tyler-Walters 2014). As a result: • the state of knowledge on the effects of each pressure on circalittoral and offshore benthos was reviewed; • the resistance, resilience and, hence, sensitivity of sixteen ecological groups, representing 96 characteristic species, were assessed for eight separate pressures; • each assessment was accompanied by a detailed review of the relevant evidence; Assessing the sensitivity of subtidal sedimentary habitats to pressures associated with human activities • knowledge gaps and sources of uncertainty were identified for each group; • each assessment was accompanied by an assessment of the quality of the evidence, its applicability to the assessment and the degree of concordance (agreement) between the evidence, to highlight sources of uncertainty as an assessment of the overall confidence in the sensitivity assessment, and finally • limitations in the methodology and the application of sensitivity assessments were outlined. This process demonstrated that the ecological groups identified in Phase 1 (Tillin & Tyler-Walters 2014) were viable groups for sensitivity assessment, and could be used to represent the 33 circalittoral and offshore sediments biotopes identified at the beginning of the project. The results of the sensitivity assessments show: • the majority of species and hence ecological groups in sedimentary habitats are sensitive to physical change, especially loss of habitat and sediment extraction, and change in sediment type; • most sedimentary species are sensitive to physical damage, e.g. abrasion and penetration, although deep burrowing species (e.g. the Dublin Bay prawn - Nephrops norvegicus and the sea cucumber - Neopentadactyla mixta) are able to avoid damaging effects to varying degrees, depending on the depth of penetration and time of year; • changes in hydrography (wave climate, tidal streams and currents) can significantly affect sedimentary communities, depending on whether they are dominated by deposit, infaunal feeders or suspension feeders, and dependant on the nature of the sediment, which is itself modified by hydrography and depth; • sedentary species and ecological groups that dominate the top-layer of the sediment (either shallow burrowing or epifaunal) remain the most sensitive to physical damage; • mobile species (e.g. interstitial and burrowing amphipods, and perhaps cumaceans) are the least sensitive to physical change or damage, and hydrological change as they are already adapted to unstable, mobile substrata; • sensitivity to changes in organic enrichment and hence oxygen levels, is variable between species and ecological groups, depending on the exact habitat preferences of the species in question, although most species have at least a medium sensitivity to acute deoxygenation; • there is considerable evidence on the effects of bottom-contact fishing practices and aggregate dredging on sedimentary communities, although not all evidence is directly applicable to every ecological group; • there is lack of detailed information on the physiological tolerances (e.g. to oxygenation, salinity, and temperature), habitat preferences, life history and population dynamics of many species, so that inferences has been made from related species, families, or even the same phylum; • there was inadequate evidence to assess the effects of non-indigenous species on most ecological groups, and Assessing the sensitivity of subtidal sedimentary habitats to pressures associated with human activities • there was inadequate evidence to assess the effects of electromagnetic fields and litter on any ecological group. The resultant report provides an up-to-date review of current knowledge about the effects of pressures resulting from human activities of circalittoral and offshore sedimentary communities. It provides an evidence base to facilitate and support the provision of management advice for Marine Protected Areas, development of UK marine monitoring and assessment, and conservation advice to offshore marine industries. However, such a review will require at least annual updates to take advantage of new evidence and new research as it becomes available. Also further work is required to test how ecological group assessments are best combined in practice to advise on the sensitivity of a range of sedimentary biotopes, including the 33 that were originally examined.

Malignancy and mortality in a population-based cohort of patients with coeliac disease or 'gluten sensitivity'

Aim: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland.

Methods: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated.

Results: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin anti-bodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population.

Conclusion: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity. © 2007 The WJG Press. All rights reserved.

Use of breakpoint combination sensitivity testing as a simple and convenient method to evaluate the combined effects of ceftazidime and tobramycin on Pseudomonas aeruginosa and Burkholderia cepacia complex isolates in vitro

An in vitro method of determining the activity of antibiotics in combination which is simple and convenient to perform and which could be used routinely in clinical microbiology laboratories is desirable. We investigated the activity, against Pseudomonas aeruginosa and Burkholderia cepacia complex clinical isolates, of ceftazidime and tobramycin in combination using a broth macrodilution sensitivity method based on breakpoint minimum inhibitory concentrations and compared the results obtained using this method with those obtained using the microtitre checkerboard method. There was good agreement in interpretation of results between the two methods for both P. aeruginosa (90%) and B. cepacia complex isolates (70%) with tobramycin and for P. aeruginosa isolates (70%) with ceftazidime. As the breakpoint combination sensitivity testing method employs only four tubes and does not require initial determination of individual antibiotic minimum inhibitory concentrations, it is simpler and more convenient for determining the activity of antibiotics in combination than the microtitre checkerboard method. The use of this method in routine microbiology laboratories to determine the activity of antibiotic combinations against clinical isolates should optimise treatment of infection by ensuring that appropriate antibiotic combinations are prescribed. (C) 2004 Elsevier B.V. All rights reserved.

Antibacterial activities of naturally occurring compounds against antibiotic-resistant Bacillus cereus vegetative cells and spores, Escherichia coli, and Staphylococcus aureus

After demonstrating the lack of effectiveness of standard antibiotics against the acquired antibiotic resistance of Bacillus cereus (NCTC 10989), Escherichia coli (NCTC 1186), and Staphylococcus aureus (ATCC 12715), we showed that the following natural substances were antibacterial against these resistant pathogens: cinnamon oil, oregano oil, thyme oil, carvacrol, (S)-perillaldehyde, 3,4-dihydroxybenzoic acid (beta-resorcylic acid), and 3,4-dihydroxyphenethylamine (dopamine). Exposure of the three pathogens to a dilution series of the test compounds showed that oregano oil was the most active substance. The oils and pure compounds exhibited exceptional activity against B. cereus vegetative cells, with oregano oil being active at nanogram, per milliliter levels. In contrast, activities against B. cereus spores were very low. Activities of the test compounds were in the following approximate order: oregano oil > thyme oil approximate to carvacrol > cinnamon oil > perillaldehyde > dopamine > beta-resorcylic acid. The order of susceptibilities of the pathogens to inactivation was as follows: B. cereus (vegetative) much greater than S. aureus approximate to E. coli much greater than B. cereus (spores). Some of the test substances may be effective against antibiotic-resistant bacteria in foods and feeds.