A miniature bioassay for testing the acute phytotoxicity of photosystem II herbicides on seagrass

© 2015 Wilkinson et al. Photosystem II (PSII) herbicides have been detected in nearshore tropical waters such as those of the Great Barrier Reef and may add to the pressure posed by runoff containing sediments and nutrients to threatened seagrass habitats. There is a growing number of studies into the potential effects of herbicides on seagrass, generally using large experimental set-ups with potted plants. Here we describe the successful development of an acute 12-well plate phytotoxicity assay for the PSII herbicide Diuron using isolated Halophila ovalis leaves. Fluorescence images demonstrated Diuron affected the entire leaf surface evenly and responses were not influenced by isolating leaves from the plant. The optimum exposure duration was 24 h, by which time the inhibition of effective quantum yield of PSII (ΔF/Fm′) was highest and no deterioration of photosystems was evident in control leaves. The inhibition of ΔF/Fm′ by Diuron in isolated H. ovalis leaves was identical to both potted and hydroponically grown plants (with leaves remaining attached to rhizomes), indicating similar reductions in photosynthetic activity in these acute well-plate assays. The sensitivity of the assay was not influenced by irradiance (range tested 40 to 400 μmol photons m-2 s-1). High irradiance, however, caused photo-oxidative stress in H. ovalis and this generally impacted in an additive or sub-additive way with Diuron to damage PSII. The bioassay using isolated leaves is more rapid, uses far less biological material and does not rely on specialised aquarium facilities in comparison with assays using potted plants. The development and validation of this sensitive bioassay will be useful to reliably screen and monitor the phytotoxicity of existing and emerging PSII herbicides and contribute to risk assessments and water quality guideline development in the future

SCN1A variants from bench to bedside-improved clinical prediction from functional characterization

Variants in the SCN1A gene are associated with a wide range of disorders including genetic epilepsy with febrile seizures plus (GEFS+), familial hemiplegic migraine (FHM), and the severe childhood epilepsy Dravet syndrome (DS). Predicting disease outcomes based on variant type remains challenging. Despite thousands of SCN1A variants being reported, only a minority has been functionally assessed. We review the functional SCN1A work performed to date, critically appraise electrophysiological measurements, compare this to in silico predictions, and relate our findings to the clinical phenotype. Our results show, regardless of the underlying phenotype, that conventional in silico software correctly predicted benign from pathogenic variants in nearly 90%, however was unable to differentiate within the disease spectrum (DS vs. GEFS+ vs. FHM). In contrast, patch‐clamp data from mammalian expression systems revealed functional differences among missense variants allowing discrimination between disease severities. Those presenting with milder phenotypes retained a degree of channel function measured as residual whole‐cell current, whereas those without any whole‐cell current were often associated with DS (p = .024). These findings demonstrate that electrophysiological data from mammalian expression systems can serve as useful disease biomarker when evaluating SCN1A variants, particularly in view of new and emerging treatment options in DS

Scintigraphic assessment of bone status at one year following hip resurfacing : comparison of two surgical approaches using SPECT-CT scan

Objectives: To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches. Methods: In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach. Results: One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy. Conclusions: Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery

Industry-supported meta-analyses compared with meta-analyses with non-profit or no support: Differences in methodological quality and conclusions

<p>Abstract</p> <p>Background</p> <p>Studies have shown that industry-sponsored meta-analyses of drugs lack scientific rigour and have biased conclusions. However, these studies have been restricted to certain medical specialities. We compared all industry-supported meta-analyses of drug-drug comparisons with those without industry support.</p> <p>Methods</p> <p>We searched PubMed for all meta-analyses that compared different drugs or classes of drugs published in 2004. Two authors assessed the meta-analyses and independently extracted data. We used a validated scale for judging the methodological quality and a binary scale for judging conclusions. We divided the meta-analyses according to the type of support in 3 categories: industry-supported, non-profit support or no support, and undeclared support.</p> <p>Results</p> <p>We included 39 meta-analyses. Ten had industry support, 18 non-profit or no support, and 11 undeclared support. On a 0–7 scale, the median quality score was 6 for meta-analyses with non-profit or no support and 2.5 for the industry-supported meta-analyses (P < 0.01). Compared with industry-supported meta-analyses, more meta-analyses with non-profit or no support avoided bias in the selection of studies (P = 0.01), more often stated the search methods used to find studies (P = 0.02), searched comprehensively (P < 0.01), reported criteria for assessing the validity of the studies (P = 0.02), used appropriate criteria (P = 0.04), described methods of allocation concealment (P = 0.05), described methods of blinding (P = 0.05), and described excluded patients (P = 0.08) and studies (P = 0.15). Forty percent of the industry-supported meta-analyses recommended the experimental drug without reservations, compared with 22% of the meta-analyses with non-profit or no support (P = 0.57).</p> <p>In a sensitivity analysis, we contacted the authors of the meta-analyses with undeclared support. Eight who replied that they had not received industry funding were added to those with non-profit or no support, and 3 who did not reply were added to those with industry support. This analysis did not change the results much.</p> <p>Conclusion</p> <p>Transparency is essential for readers to make their own judgment about medical interventions guided by the results of meta-analyses. We found that industry-supported meta-analyses are less transparent than meta-analyses with non-profit support or no support.</p

Deconstructing the lesbian, gay, bisexual, transgender victim of sex trafficking: Harm, exceptionality and religion–sexuality tensions

Contrary to widespread belief, sex trafficking also targets lesbian, gay, bisexual, transgender (LGBT) communities. Contemporary social and political constructions of victimhood lie at the heart of regulatory policies on sex trafficking. Led by the US Department of State, knowledge about LGBT victims of trafficking constitutes the newest frontier in the expansion of criminalization measures. These measures represent a crucial shift. From a burgeoning range of preemptive measures enacted to protect an amorphous class of ‘all potential victims’, now policies are heavily premised on the risk posed by traffickers to ‘victims of special interest’. These constructed identities, however, are at odds with established structures. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of LGBT trafficking victims. Specifically, the article argues that discourses of ‘exceptional vulnerability’ and the polarized notions of ‘innocence’ and ‘guilt’ inform hierarchies of victimhood. Based on these insights, the article argues for the need to move beyond monolithic understandings of victims, by reframing the politics of harm accordingly

A prospective study of hearing changes after beginning zidovudine or didanosine in HIV-1 treatment-naïve people

BACKGROUND: While hearing loss in HIV-infected people after beginning nucleoside reverse transcriptase inhibitors (NRTIs) has been reported, there have been no prospective studies that measured hearing changes longitudinally in treatment-naïve HIV-infected subjects following initiation of regimens containing NRTIs. The goal of this study was to conduct a prospective assessment of the contribution of zidovudine (ZDV) and didanosine (ddI) to hearing loss METHODS/DESIGN: A prospective observational pilot study to determine whether ZDV or ddI, alone or in combination, are associated with sensorineural hearing loss in HIV-infected persons. Changes in hearing levels at all frequencies and in low and high frequency pure tone averages were measured at baseline, 16, and 32 weeks after initiating antiretroviral therapy. DISCUSSION: Treatment with ZDV and ddI did not result in loss of hearing, even after taking into account noise exposure, immune status and age. The results of this prospective pilot study do not support the notion that treatment with nucleoside antiretrovirals damages hearing

Management Approach : The Virtuous Corporation as a Moral Agent for Sustainable Development

This chapter examines the corporation as a moral agent for sustainable development. While sustainable development in business organizations can be argued from utility-and duty-based ethical theories, it is suggested that virtue-based ethics is needed to develop a moral agency for sustainable development, as it focuses on the organizational character. In addition, it is proposed that the biosphere (the global sum of all ecosystems) is accepted as the ultimate principal for all planetary agents to avoid an anthropocentric and only inward-looking position typical for ethical theories. Thus, a business organization can work as a nexus for virtue and develop a moral agency that contributes to the well-being of the biosphere and all of its members.Peer reviewe

Excess Pressure Integral Predicts Cardiovascular Events Independent of Other Risk Factors in the Conduit Artery Functional Evaluation Substudy of Anglo-Scandinavian Cardiac Outcomes Trial

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.