Investigation of organic xenobiotic transfers, partitioning and processing in air-soil-plant systems using a microcosm apparatus. Part II:comparing the fate of chlorobenzenes in grass planted soil

A microcosm system was used to investigate and compare transfers of 14C labeled-1,2-dichlorobenzene (DCB), 1,2,4-trichlorobenzene (TCB) and hexachlorobenzene (HCB) in an air-soil-plant system using single grass tillers planted into spiked soil. This study was the second phase of a development investigation for eventual study of a range of xenobiotic pollutants. Recoveries from the system were excellent at >90%. The predominant loss pathway for 14C labeled-1,2-DCB and 1,2,4-TCB was volatilisation with 85% and 76% volatilisation of parent compound and volatile metabolites over 5 weeks respectively. Most of the added label in the hexachlorobenzene spiked system remained in soil. Mineralisation was

Fasciola hepatica:Histological demonstration of apoptosis in the reproductive organs of flukes of triclabendazole-sensitive and triclabendazole-resistant isolates, and in field-derived flukes from triclabendazole-treated hosts, using in situ hybridisation to visualise endonuclease-generated DNA strand breaks

Investigation of the triclabendazole (TCBZ) resistance status of populations of Fasciola hepatica in field cases of fasciolosis, where treatment failure has been reported, can be supported by histological examination of flukes collected from recently treated hosts. In TCBZ-sensitive flukes (TCBZ-S) exposed to TCBZ metabolites for 1-4. days in vivo, but not in TCBZ-resistant flukes (TCBZ-R), morphological changes suggestive of apoptosis occur in cells undergoing meiosis or mitosis in the testis, ovary and vitelline follicles. In order to verify or refute the contention that efficacy of TCBZ treatment is associated with apoptosis in the reproductive organs of flukes, histological sections of TCBZ-S (Cullompton isolate) flukes and TCBZ-R (Sligo isolate) flukes were subjected to the TdT-mediated dUDP nick end labelling (TUNEL) in situ hybridisation method, a commercially available test specifically designed to label endonuclease-induced DNA strand breaks associated with apoptosis. Additionally, sections of in vivo-treated and untreated flukes originating from field outbreaks of suspected TCBZ-S and TCBZ-R fasciolosis were labelled by the TUNEL method. It was found that in treated TCBZ-S flukes, strong positive labelling indicating apoptosis was associated with morphologically abnormal cells undergoing mitosis or meiosis in the testis, ovary and vitelline follicles. Background labelling in the positive testis sections was attributed to heterophagy of cell debris by the sustentacular tissue. The triggering of apoptosis was probably related to failure of spindle formation at cell division, supporting the contention that TCBZ inhibits microtubule formation. In treated TCBZ-R (Sligo Type 1) flukes, and in treated flukes from field outbreaks of suspected TCBZ-R fasciolosis, no significant labelling was observed, while sections of fluke derived from a field case of fasciolosis where TCBZ resistance was not suspected were heavily labelled. Light labelling was associated with the testis of untreated Cullompton (TCBZ-S) and Sligo Type 2 (TCBZ-R) flukes, which exhibit abnormal spermatogenesis and spermiogenesis, respectively. This was attributed to apoptosis and to heterophagy of effete germ line cells by the sustentacular tissue. It is concluded that demonstration of apoptosis by in situ hybridisation using the TUNEL method on sections of 1-4. days in vivo TCBZ-treated F. hepatica can contribute to the diagnosis of TCBZ resistance in field outbreaks of fasciolosis. © 2012 Elsevier B.V.

Tea tree oil (5%) body wash versus standard care (Johnson's Baby Softwash) to prevent colonization with methicillin-resistant Staphylococcus aureus in critically ill adults::a randomized controlled trial

OBJECTIVES: To determine whether the daily use of 5% tea tree oil (TTO) body wash (Novabac 5% Skin Wash) compared with standard care [Johnson's Baby Softwash (JBS)] had a lower incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization.

PATIENTS: The study setting was two intensive care units (ICUs; mixed medical, surgical and trauma) in Northern Ireland between October 2007 and July 2009. The study population comprised 391 patients who were randomized to JBS or TTO body wash.

METHODS: This was a Phase 2/3, prospective, open-label, randomized, controlled trial. Trial registration: ISRCTN65190967. The primary outcome was new MRSA colonization during ICU stay. Secondary outcomes included the incidence of MRSA bacteraemia and maximum increase in sequential organ failure assessment score.

RESULTS: A total of 445 patients were randomized to the study. After randomization, 54 patients were withdrawn; 30 because of a positive MRSA screen at study entry, 11 due to lack of consent, 11 were inappropriately randomized and 2 had adverse reactions. Thirty-nine (10%) patients developed new MRSA colonization (JBS n?=?22, 11.2%; TTO body wash n?=?17, 8.7%). The difference in percentage colonized (2.5%, 95% CI -?8.95 to 3.94; P?=?0.50) was not significant. The mean maximum increase in sequential organ failure assessment score was not significant (JBS 1.44, SD 1.92; TTO body wash 1.28, SD 1.79; P?=?0.85) and no study patients developed MRSA bacteraemia.

CONCLUSIONS: Compared with JBS, TTO body wash cannot be recommended as an effective means of reducing MRSA colonization.

Explaining levels of deprivation in the European Union

In this paper we seek to explain variations in levels of deprivation between EU countries. The starting-point of our analysis is the finding that the relationship between income and life-style deprivation varies across countries. Given our understanding of the manner in which the income-deprivation mismatch may arise from the limitations of current income as a measure of command over resources, the pattern of variation seems to be consistent with our expectations of the variable degree to which welfare-state regimes achieve 'decommodification' and smooth income flows. This line of reasoning suggests that cross-national differences in deprivation might, in significant part, be due not only to variation in household and individual characteristics that are associated with disadvantage but also to the differential impact of such variables across countries and indeed welfare regimes. To test this hypothesis, we have taken advantage of the ECHP (European Community Household Panel) comparative data set in order to pursue a strategy of substituting variable names for country/welfare regime names. We operated with two broad categories of variables, tapping, respectively, needs and resources. Although both sets of factors contribute independently to our ability to predict deprivation, it is the resource factors that are crucial in reducing country effects. The extent of cross-national heterogeneity depends on specifying the social class and situation in relation to long-term unemployment of the household reference person. The impact of the structural socio-economic variables that we label 'resource factors' varies across countries in a manner that is broadly consistent with welfare regime theory and is the key factor in explaining cross-country differences in deprivation. As a consequence, European homogeneity is a great deal more evident among the advantaged than the disadvantaged.

Human growth hormone and the temptations of biomedical enhancement

It is likely that humans have sought enhancements for themselves or their children for as long as they have recognised that improvements in individuals are a possibility. One genre of self-improvement in modern society can be called 'biomedical enhancements'. These include drugs, surgery and other medical interventions aimed at improving the mind, body or performance. This paper uses the case of human growth hormone (hGH) to examine the social nature of enhancements. Synthetic hGH was developed in 1985 by the pharmaceutical industry and was approved by the FDA for very specific uses, particularly treatment of growth hormone deficiency. However, it has also been promoted for a number of 'off label' uses, most of which can be deemed enhancements. Drugs approved for one treatment pave the way for use as enhancements for other problems. Claims have been made for hGH as a treatment for idiopathic shortness, as an anti-ageing agent and to improve athletic performance. Using the hGH case, we are able to distinguish three faces of biomedical enhancement: normalisation, repair and performance edge. Given deeply ingrained social and individual goals in American society, the temptations of biomedical enhancements provide inducement for individuals and groups to modify their situation. We examine the temptations of enhancement in terms of issues such as unnaturalness, fairness, risk and permanence, and shifting social meanings. In our conclusions, we outline the potentials and pitfalls of biomedical enhancement.

A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor

Herein, we present the use of a single gold nanorod sensor for detection of diseases on an antibody-functionalized surface, based on antibody–antigen interaction and the localized surface plasmon resonance (LSPR) ?max shifts of the resonant Rayleigh light scattering spectra. By replacing the cetyltrimethylammonium bromide (CTAB), a tightly packed self-assembled monolayer of HS(CH2)11(OCH2CH2)6OCH2COOH(OEG6) has been successfully formed on the gold nanorod surface prior to the LSPR sensing, leading to the successful fabrication of individual gold nanorod immunosensors. Using prostate specific antigen (PSA) as a protein biomarker, the lowest concentration experimentally detected was as low as 111 aM, corresponding to a 2.79 nm LSPR ?max shift. These results indicate that the detection platform is very sensitive and outperforms detection limits of commercial tests for PSA so far. Correlatively, its detection limit can be equally compared to the assays based on DNA biobarcodes. This study shows that a gold nanorod has been used as a single nanobiosensor to detect antigens for the first time; and the detection method based on the resonant Rayleigh scattering spectrum of individual gold nanorods enables a simple, label-free detection with ultrahigh sensitivity.

Engineering of Vis-NIR Metamaterials towards Revolutionary Ultrasensitive and Versatile Plasmonic Biosensors

By enabling subwavelength light localization and strong electromagnetic field enhancement, plasmonic biosensors have opened up a new realm of possibilities for a broad range of chemical and biological sensing applications owing to their label-free and real-time attributes. Although significant progress has been made, many fundamental and practical challenges still remain to be addressed. For instance, the plasmonic biosensors are nonselective sensing platforms; they are not well-suited to provide information regarding conformation or chemical fingerprint of unknown biomolecules. Furthermore, tunability of the plasmonic resonance in visible frequency regime is still limited; this will prevent their efficient and reproducible exploitation in single-molecule sensitivity. Here, we show that by engineering geometry of plasmonic metamaterials,1 consisting of periodic arrays of artificial split-ring resonators (SRRs), the plasmonic resonance of metamaterials could be tuned to visible-near infrared regimes (Vis-NIR) such that it allows parallel acquisition of optical transmission and highly surface-enhanced Raman (SERS) spectra from large functionalized SRR arrays. The Au SRRs were designed in form of alphabet letters (U, V, S, H, Y) with various line width (from 80 to 30 nm). By tailoring their size and shape, plasmonic resonance wavelength of the SRRs could be actively tuned so that it gives the strongest SERS effect under given excitation energy and polarization for biological and organic molecules. On the other hand, the plasmonic tunability was also achieved for a given SRR pattern by tuning the laser wavelength to obtain the highest electromagnetic field enhancement. The geometry- and laser-tunable channels typically provide an electromagnetic field enhancement as high as 20 times. This will provide the basis of versatile and multichannel devices for identification of different conformational states of Guanine-rich DNA, detection of a cancer biomarker nucleolin, and femtomolar sensitivity detection of food and drink additives. These results show that the tunable Vis-IR metamaterials are very versatile biosensing platforms and suggest considerable promise in genomic research, disease diagnosis, and food safety analysis.

Development of M13 bacteriophage-based SPR detection using Salmonella detection as a case study

Surface plasmon resonance (SPR)-based biosensor is a popular platform for real-time monitoring and sensitive detection for a myriad of targets. However, only a few studies have reported the use of bacteriophages as specific binders for SPR-based detection. This study aimed to demonstrate how filamentous M13 bacteriophages expressing 12-mer peptides can be employed in an SPR-based assay, using a Salmonella-specific bacteriophage as a model binder to detect the foodborne bacterium Salmonella. Several important factors (immobilization buffers and methods, and interaction buffers) for a successful bacteriophage-based SPR assay were optimized. As a result, a Salmonella-specific bacteriophage-based SPR assay was achieved, with very low cross reactivity with other non-target foodborne pathogens and detection limits of 8.0 × 10⁷ and 1.3 × 10⁷ CFU/mL for one-time and five-time immobilized sensors, respectively. This proof-of-concept study demonstrates the feasibility of using M13 bacteriophages expressing target-specific peptides as a binder in a rapid and label-free SPR assay for pathogen detection.

Nile blue-based nano-sized pH sensors for simultaneous far-red and near-infrared live bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.

Food miles or carbon emissions? Exploring labeling preference for food transport footprint with a stated choice study

The ecological footprint of food transport can be communicated using carbon dioxide emissions (CO2 label) or by providing information about both the length of time and the mileage travelled (food miles label). We use stated choice data to estimate conventional unobserved taste heterogeneity models and extend them to a specification that also addresses attribute nonattendance. The implied posterior distributions of the marginal willingness to pay values are compared graphically and are used in validation regressions. We find strong bimodality of taste distribution as the emerging feature, with different groups of subjects having low and high valuations for these labels. The best fitting model shows that CO2 and food miles valuations are much correlated. CO2 valuations can be high even for those respondents expressing low valuations for food miles. However, the reverse is not true. Taken together, the results suggest that consumers tend to value the CO2 label at least as much and sometimes more than the food miles label.

An evaluation of the capability of a biolayer interferometry biosensor to detect low-molecular-weight food contaminants

The safety of our food is an essential requirement of society. One well-recognised threat is that of chemical contamination of our food, where low-molecular-weight compounds such as biotoxins, drug residues and pesticides are present. Low-cost, rapid screening procedures are sought to discriminate the suspect samples from the population, thus selecting only these to be forwarded for confirmatory analysis. Many biosensor assays have been developed as screening tools in food contaminant analysis, but these tend to be electrochemical, fluorescence or surface plasmon resonance based. An alternative approach is the use of biolayer interferometry, which has become established in drug discovery and life science studies but is only now emerging as a potential tool in the analysis of food contaminants. A biolayer interferometry biosensor was assessed using domoic acid as a model compound. Instrument repeatability was tested by simultaneously producing six calibration curves showing replicate repeatability (n = 2) ranging from 0.1 to 6.5 % CV with individual concentration measurements (n = 12) ranging from 4.3 to 9.3 % CV, giving a calibration curve midpoint of 7.5 ng/ml (2.3 % CV (n = 6)). Reproducibility was assessed by producing three calibration curves on different days, giving a midpoint of 7.5 ng/ml (3.4 %CV (n = 3)). It was further shown, using assay development techniques, that the calibration curve midpoint could be adjusted from 10.4 to 1.9 ng/ml by varying assay parameters before the simultaneous construction of three calibration curves in matrix and buffer. Sensitivity of the assay compared favourably with previously published biosensor data for domoic acid. © 2013 Springer-Verlag Berlin Heidelberg.

A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia

Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P = 0·06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P = 0·03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P = 0·006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.

Who Feels Inferior? A Test of the Status Anxiety Hypothesis of Social Inequalities in Health

The empirical association between income inequality, population health and other social problems is now well established and the research literature suggests that the relationship is not artefactual. Debate is still ongoing as to the cause of this association. Wilkinson, Marmot and colleagues have argued for some time that the relationship stems from the psycho-social effects of status comparisons. Here, income inequality is a marker of a wider status hierarchy that provokes an emotional stress response in individuals that is harmful to health and well-being. We label this the ‘status anxiety hypothesis’. If true, this would imply a structured relationship between income inequality at the societal level, individual income rank and anxiety relating to social status. This paper sets out strong and weak forms of the hypothesis and then presents three predictions concerning the structuring of ‘status anxiety’ at the individual level given different levels of national income inequality and varying individual income. We then test these predictions using data from a cross-national survey of over 34,000 individuals carried out in 2007 in 31 European countries. Respondents from low inequality countries reported less status anxiety than those in higher inequality countries at all points on the income rank curve. This is an important precondition of support for the status anxiety hypothesis and may be seen as providing support for the weaker version of the hypothesis. However, we do not find evidence to support the stronger version of the hypothesis which requires the negative effect of income rank on status anxiety to be exacerbated by increasing income inequality.

The controlled fabrication and geometry tunable optics of gold nanotube arrays

Arrays of vertically aligned gold nanotubes are fabricated over several square centimetres which display a geometry tunable plasmonic extinction peak at visible wavelengths and at normal incidence. The fabrication method gives control over nanotube dimensions with inner core diameters of 15–30 nm, wall thicknesses of 5–15 nm and nanotube lengths of up to 300 nm. It is possible to tune the position of the extinction peak through the wavelength range 600–900 nm by varying the inner core diameter and wall thickness. The experimental data are in agreement with numerical modelling of the optical properties which further reveal highly localized and enhanced electric fields around the nanotubes. The tunable nature of the optical response exhibited by such structures could be important for various label-free sensing applications based on both refractive index sensing and surface-enhanced Raman scattering.

Tailoring Plasmonic Metamaterials for DNA Molecular Logic Gates

Structural and functional information encoded in DNA combined with unique properties of nanomaterials could be of use for the construction of novel biocomputational circuits and intelligent biomedical nanodevices. However, at present their practical applications are still limited by either low reproducibility of fabrication, modest sensitivity, or complicated handling procedures. Here, we demonstrate the construction of label-free and switchable molecular logic gates that use specific conformation modulation of a guanine- and thymine- rich DNA, while the optical readout is enabled by the tunable alphabetical metamaterials, which serve as a substrate for surface enhanced Raman spectroscopy (MetaSERS). By computational and experimental investigations, we present a comprehensive solution to tailor the plasmonic responses of MetaSERS with respect to the metamaterial geometry, excitation energy, and polarization. Our tunable MetaSERS-based DNA logic is simple to operate, highly reproducible, and can be stimulated by ultra-low concentration of the external inputs, enabling an extremely sensitive detection of mercury ions.