Political Posturing or Real Powers: Control of Genetically Modified Crops by the Member States and their Regions

The cultivation of genetically modified (GM) crops in the EU is highly harmonised, involving a central authorisation procedure that aims to ensure a high level of environmental and human health protection. However conflicts over authority persist and the Commission has responded to a combination of internal and external pressures with a more flexible approach to coexistence, a proposed opt-out clause and recently a promise by the head of the Commission to review the existing EU GM legislative regime, providing an opportunity to consider and suggest paths of development. In light of the significance of multilevel governance and subsidiarity for GM cultivation, this paper considers the policy-making powers of the Member States and subnational regions in this regime, focussing upon post-authorisation options in particular. A number of core mechanisms exist, including voluntary measures, safeguard clauses, coexistence measures, a proposed express opt-out and Article 4(2) TEU on ‘national identity. These mechanisms are examined in light of the goals and challenges of multilevel governance, in order to consider whether the relevant powers are located at the appropriate level. Overall, it is apparent that the developments occurring at the EU level are strengthening multilevel governance, but with significant opportunities to improve it further through focussing on the supporting roles and the regional levels in particular.

Biofilm Eradication Kinetics of the Ultrashort Lipopeptide C12-OOWW-NH2 Utilizing a Modified MBEC Assay™

In this study, we report the antimicrobial planktonic and biofilm kill kinetics of ultrashort cationic lipopeptides previously demonstrated by our group to have a minimum biofilm eradication concentration (MBEC) in the microgram per mL (μg/mL) range against clinically relevant biofilm-forming micro-organisms. We compare the rate of kill for the most potent of these lipopeptides, dodecanoic (lauric) acid-conjugated C₁₂-Orn-Orn-Trp-Trp-NH₂ against the tetrapeptide amide H-Orn-Orn-Trp-Trp-NH₂ motif and the amphibian peptide Maximin-4 via a modification of the MBEC Assay™ for Physiology & Genetics (P&G). Improved antimicrobial activity is achieved upon N-terminal lipidation of the tetrapeptide amide. Increased antimicrobial potency was demonstrated against both planktonic and biofilm forms of Gram-positive micro-organisms. We hypothesize rapid kill to be achieved by targeting of microbial membranes. Complete kill against established 24-h Gram-positive biofilms occurred within 4 h of exposure to C₁₂-OOWW-NH₂ at MBEC values [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 15.63 μg/mL] close to the values for the planktonic minimum inhibitory concentration (MIC) [methicillin-resistant Staphylococcus epidermidis (ATCC 35984): 1.95 μg/mL]. Such rapid kill, especially against sessile biofilm forms, is indicative of a reduction in the likelihood of resistant strains developing with the potential for quicker resolution of pathogenic infection. Ultrashort antimicrobial lipopeptides have high potential as antimicrobial therapy.

Evaluation of the Factors Contributing to Levonorgestrel Binding in Addition Cure Silicone Elastomer Vaginal Rings

Background: Following progress of the dapivirine (DPV)-releasing silicone elastomer (SE) vaginal ring (VR) into Phase III clinical studies, there is now interest in developing next-generation rings that additionally provide contraception. Levonorgestrel (LNG) is a safe and effective progestin that is being widely considered for use as a hormonal contraceptive agent in future multipurpose prevention technology (MPT) products. Although LNG has previously been incorporated into various controlled release SE devices, minimal attention has focused on its propensity to irreversibly react with addition cure SE systems. Here, for the first time, we investigate this LNG binding phenomenon and outline strategies for overcoming it.
Methods: VRs containing various loadings of DPV and LNG were manufactured and in vitro release assessed. Different LNG-only SE samples were also prepared to assess the following parameters: (i) addition cure vs. condensation cure SEs; (ii) different types of addition cure SEs; (iii) mixing time, (iv) cure temperature, (v) cure time; and (vi) LNG particle size. After manufacture, the LNG-only samples were assayed for total drug content using a solvent extraction method. The SE curing reaction and the LNG binding reaction was probed using nuclear magnetic resonance (NMR) spectroscopy. Results:
Under certain drug/formulation/processing conditions, LNG was not recoverable from VRs. Further studies using non-ring samples showed that: (a) the phenomenon was only observed with addition cure SEs (and not condensation cure SEs); (b) the extent of binding was dependent upon the type of addition cure SE; (c) micronised LNG showed significantly greater binding than non-micronised LNG; (d) the extent of binding correlated with increased mixing time, cure time and cure temperature.
Conclusions: Careful control of the API characteristics, the SE composition, and the manufacturing conditions will be necessary to establish a practical VR formulation for controlled release of LNG.

Role of capsular modified heptose in the virulence of Campylobacter jejuni

The Campylobacter jejuni capsular polysaccharide is important for virulence and often contains a modified heptose. In strain ATCC 700819 (a.k.a. NCTC 11168), the modified heptose branches off from the capsular backbone and is directly exposed to the environment. We reported previously that the enzymes encoded by wcaG, mlghB and mlghC are involved in heptose modification. Here, we show that inactivation of any of these genes leads to production of capsule lacking modified heptose and alters the transcription of other capsule modification genes differentially. Inactivation of mlghB or mlghC, but not of wcaG, decreased susceptibility to bile salts and abrogated invasion of intestinal cells. All mutants showed increased sensitivity to serum killing, especially wcaG::cat, and had defects in colonization and persistence in chicken intestine, but did not show significant differences in adhesion, phagocytosis and intracellular survival in murine macrophages. Together, our findings suggest that the capsular heptose modification pathway contributes to bacterial resistance against gastrointestinal host defenses and supports bacterial persistence via its role in serum resistance and invasion of intestinal cells. Our data further suggest a dynamic regulation of expression of this pathway in the gastrointestinal tract.

Regulating Genetically Modified Organisms in Ireland – Laissez faire approach?

This chapter examines the legal framework applicable to genetically modified organisms (GMOs) in Ireland, bearing in mind the limited presence of GMOs. As a member of the European Union (EU), a specific, process-based regime applies regarding the authorisation and regulation of GMOs. This is intended to ensure a high level of environmental and human health protection and also enable producer and consumer choice. This regime is highly harmonized, but allows some flexibility regarding its implementation and, soon, the potential to opt-out from cultivation in part or entirely. Although, Ireland has only legislated on the area to the extent and in the manner required by the EU, it may avail of the opt-out in future – understandable in light of the lack of any cultivation currently and the green image of Ireland.
Complementary horizontal legislation and common law principles, relevant to labelling and varying forms of liability, deal with most issues that might arise quite comprehensively. However, they are quite complicated, overlapping and untailored and it is worth considering whether specific legislation should be developed to deal with liability related to GMOs.
Overall, Ireland holds varying stances to different forms of GMOs, with the greatest acceptance and use of GM-feed for pragmatic reasons. It has not developed a specific Irish approach, copy-pasting EU legislation and relying upon existing law to deal with any issues. This is understandable in light of the high level of harmonization and limited presence of GMOs in Ireland, but nonetheless will need to be developed as the availability of GMOs increases.

Attaining Subsidiarity-Based Multilevel Governance of Genetically Modified Cultivation?

The cultivation of genetically modified (GM) crops in the EU is highly harmonised, but with persisting conflicts over authority. The Commission responded to internal and external pressures with a more flexible approach to coexistence, a proposed opt-out clause and a promise to review the existing EU GM regime, providing an opportunity to consider and suggest paths of development. This article considers the post-authorisation policy-making powers of Member States and subnational regions, in light of subsidiarity-based multilevel governance. It considers the different approaches to risk-centred issues and more general policy choices. Overall, the developments occurring at the EU level are strengthening subsidiarity-based multilevel governance within the GM cultivation regime, but with significant opportunities to improve it further through focussing on the complementary powers, coordination and the regional levels in particular.

Plasmon enhanced fluorescence studies from aligned gold nanorod arrays modified with SiO2 spacer layers

Here, we demonstrate that quasi self-standing Au nanorod arrays prepared with plasma polymerisation deposited SiO2 dielectric spacers support surface enhanced fluorescence (SEF) while maintaining high signal reproducibility. We show that it is possible to find a balance between enhanced radiative and non-radiative decay rates at which the fluorescent intensity is maximized. The SEF signal optimised with a 30 nm spacer layer thickness showed a 3.5-fold enhancement with a signal variance of <15% thereby keeping the integrity of the nanorod array. We also demonstrate the decreased importance of obtaining resonance conditions when localized surface plasmon resonance is positioned within the spectral region of Au interband transitions. Procedures for further increasing the SEF enhancement factor are also discussed.

Action Spectra of P25 TiO2 and a visible light absorbing, carbon-modified titania in the photocatalytic degradation of stearic acid

The photonic efficiencies of films of Evonik (formerly Degussa) P25 TiO2 and carbon-modified TiO2 Kronos VLP 7000 samples are reported as a function of excitation wavelength (300–430 nm; FWHM ∼ 7.5 nm), i.e. the action spectra, for the degradation of stearic acid, a model organic for the photocatalytic destruction of solid surface organic pollutants. For each of these semiconductor photocatalysts, at 365 nm (FWHM = 18 nm), the dependence of the rate of degradation of stearic acid, upon the irradiance, I, is determined and the rate is found to be proportional to I0.65 and I0.82 for P25 and Kronos titania, respectively. Assuming this relationship holds at all wavelengths, the action spectra for two different semiconductor photocatalysts is modified by plotting, (RSA (rate of stearic acid destruction, units: molecules cm−2 s−1)/Iθ) vs. wavelength of excitation (λexcit), and both differ noticeably from those of the original (unmodified) action spectra, which are plots of (RSA/I = photonic efficiency, ξ) vs. λexcit. The shape of the modified action spectrum for P25 TiO2 is consistent with that reported by others for other organic mineralisation reactions and correlates well with diffuse reflectance data for P25 TiO2 (Kubelka–Munk plot), although there is some evidence that the active phase, in the photodegradation of stearic acid, is the anatase form present in P25. The unmodified and modified action spectra of the beige Kronos VLP 7000 TiO2 compound exhibits little or no activity in the visible i.e. (λexcit > 400 nm) and a peak at 350 nm. The Kronos powder contains a yellow/brown conjugated, extractable, organic sensitiser which has been identified by others as the species responsible for its reported photocatalytic visible light activity. But, irradiation of the Kronos powder film, with and without a stearic acid coating, in air, using UVA or visible light, bleaches rapidly (<60 min) most, if not all, of the little colour exhibited by the original Kronos powder. The photobleached form of the Kronos has a similar action spectrum to that of the unbleached form, which, in turn, appears very similar to that of P25 titania, at wavelengths >350 nm. It is proposed that the difference between the Kronos and P25 powder films at wavelengths <350 nm is due to a photodegradation-resistant, previously unidentified (but extractable using MeCN) UV-absorbing organic species in the former which screens the titania particles at these lower wavelengths. The implications of these observations are discussed briefly.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking

Objectives: To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. 

Methods: The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. 

Results: Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. 

Conclusions: The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects.