Bacterial fitness shapes the population dynamics of antibiotic-resistant and -susceptible bacteria in a model of combined antibiotic and anti-virulence treatment

Bacterial resistance to antibiotic treatment is a huge concern: introduction of any new antibiotic is shortly followed by the emergence of resistant bacterial isolates in the clinic. This issue is compounded by a severe lack of new antibiotics reaching the market. The significant rise in clinical resistance to antibiotics is especially problematic in nosocomial infections, where already vulnerable patients may fail to respond to treatment, causing even greater health concern. A recent focus has been on the development of anti-virulence drugs as a second line of defence in the treatment of antibiotic-resistant infections. This treatment, which weakens bacteria by reducing their virulence rather than killing them, should allow infections to be cleared through the body's natural defence mechanisms. In this way there should be little to no selective pressure exerted on the organism and, as such, a predominantly resistant population would be unlikely to emerge. However, much controversy surrounds this approach with many believing it would not be powerful enough to clear existing infections, restricting its potential application to prophylaxis. We have developed a mathematical model that provides a theoretical framework to reveal the circumstances under which anti-virulence drugs may or may not be successful. We demonstrate that by harnessing and combining the advantages of antibiotics with those provided by anti-virulence drugs, given infection-specific parameters, it is possible to identify treatment strategies that would efficiently clear bacterial infections, while preventing the emergence of resistant subpopulations. Our findings strongly support the continuation of research into anti-virulence drugs and demonstrate that their applicability may reach beyond infection prevention.Comment: Pre-review manuscript. Submitted to Journal of Theoretical Biology, July 21st 201

When Does Marketisation Lead to Privatisation? Profit-Making in English Health Services after the 2012 Health and Social Care Act

Governments world-wide have attempted to use market mechanisms and privatisation to increase the quality and/or reduce the cost of healthcare. England’s Health and Social Care Act 2012 is an attempt to promote privatisation through marketisation in the National Health Service (NHS). While the health policy literature tends to assume that privatisation follows from private-sector entry points, we argue that this is more likely if firms expect to make a profit. This paper examines the link between privatisation and marketisation in England drawing on 32 semi-structured interviews with private-sector and public-sector respondents, campaigners, and other experts conducted 6-10 months after the implementation of the 2012 Act. By generating a theoretical framework on the conditions of profitability we seek a better understanding of the conditions under which marketisation leads to privatisation. We find that significant barriers to profit-making remain after the reforms, including a top-down squeeze on prices, uncertainty in market rules, state dominance of funding and provision, and failures to depoliticise the market. These factors restrict private-sector involvement by frustrating profit-making. Where profits are made they are through reduced unit costs and high volumes by a longstanding incumbent in a particular market segment. This, however, restricts marketisation by reinforcing entry barrier

Factors influencing the dissolved iron input by river water to the open ocean

International audienceThe influence of natural metal chelators on the bio-available iron input to the ocean by river water was studied. Ferrous and ferric ions present as suspended colloidal particles maintaining the semblance of a dissolved load are coagulated and settled as their freshwater carrier is mixed with seawater at the continental boundary. However, we might argue that different iron-binding colloids become sequentially destabilized in meeting progressively increasing salinities. By use of a 59Fe tracer method, the partitioning of the iron load from the suspended and dissolved mobile fraction to storage in the sediments was measured with high accuracy in mixtures of natural river water with artificial sea water. The results show a characteristic sequence of sedimentation. Various colloids of different stability are removed from a water of increasing salinity, such as it is the case in the transition from a river water to the open sea. However, the iron transport capacities of the investigated river waters differed greatly. A mountainous river in the Austrian Alps would add only about 5% of its dissolved Fe load, that is about 2.0 µg L-1 Fe, to coastal waters. A small tributary draining a sphagnum peat-bog, which acts as a source of refractory low-molecular-weight fulvic acids to the river water, would add approximately 20% of its original Fe load, that is up to 480 µg L-1 Fe to the ocean's bio-available iron pool. This points to a natural mechanism of ocean iron fertilization by terrigenous fulvic-iron complexes originating from weathering processes occurring in the soils upstream

Origin and fluxes of atmospheric REE entering an ombrotrophic peat bog in Black Forest (SW Germany): Evidence from snow, lichens and mosses

The fate of the Rare Earth Elements (REE) were investigated in different types of archives of atmospheric deposition in the Black Forest, Southern Germany: (1) a 70 cm snow pack collected on the domed part of a raised bog and representing 2 months of snow accumulation, (2) a snow sample collected close to the road about 500 m from the peat bog, (3) two species of lichens and (4) a peat profile representing 400 years of peat accumulation as well as a “preanthropogenic” sample and the living moss layer from the top of the core. REE concentrations in peat are significantly correlated to Ti which is a lithogenic conservative element suggesting that REE are immobile in peat bog environments. Snow, lichens and peat samples show similar PAAS (Post Archean Australian Shale) normalized REE distributions suggesting that the complete atmospheric REE signal is preserved in the peat profile. However, the annual flux of REE accumulated by the peat is ca. 10 times greater than that of the bulk winter flux of REE. This difference probably indicates that the REE concentrations in the snowpack are not representative of the average REE flux over the whole year. Despite the pronounced geological differences between this site (granite host-rock) and a previously studied peat bog in Switzerland (limestone host-rock) similar REE distribution patterns and accumulation rates were found at both sites. Given that both sites confirm an Upper Continental Crust signature, the data suggests both sites are influenced by regional and not local, soil-derived lithogenic aerosols

Turnabout is fair play:use of the bacterial Multivalent Adhesion Molecule 7 as an antimicrobial agent

Pathogen attachment to host tissues is one of the initial and most crucial events during the establishment of bacterial infections and thus interference with this step could be an efficient strategy to fight bacterial colonization. Our recent work has identified one of the factors involved in initial binding of host cells by a wide range of Gram-negative pathogens, Multivalent Adhesion Molecule (MAM) 7. Interference with MAM7-mediated attachment, for example by pre-incubation of host cells with recombinant MAM7, significantly delays the onset of hallmarks of infection, such as pathogen-mediated cytotoxicity or the development of other adhesive structures such as actin pedestals. Thus, we are trying to develop tools based on MAM7 that can be used to prevent or diminish certain Gram-negative bacterial infections. Herein, we describe the use of bead-coupled MAM7 as an inhibitor of infection with the clinically relevant pathogen Pseudomonas aeruginosa

Recent atmospheric Pb deposition at a rural site in southern Germany assessed using a peat core and snowpack, and comparison with other archives

In a peat bog from Black Forest, Southern Germany, the rate of atmospheric Pb accumulation was quantified using a peat core dated by 210Pb and 14C. The most recent Pb accumulation rate (2.5 mg m−2 y−1) is similar to that obtained from a snowpack on the bog surface, which was sampled during the winter 2002 (1 to 4 mg m−2 y−1). The Pb accumulation rates recorded by the peat during the last 25 yr are also in agreement with published values of direct atmospheric fluxes in Black Forest. These values are 50 to 200 times greater than the “natural” average background rate of atmospheric Pb accumulation (20 μg m−2 y−1) obtained using peat samples from the same bog dating from 3300 to 1300 cal. yr B.C. The isotopic composition of Pb was measured in both the modern and ancient peat samples as well as in the snow samples, and clearly shows that recent inputs are dominated by anthropogenic Pb. The chronology and isotopic composition of atmospheric Pb accumulation recorded by the peat from the Black Forest is similar to the chronologies reported earlier using peat cores from various peat bogs as well as herbarium samples of Sphagnum and point to a common Pb source to the region for the past 150 years. In contrast, Pb contamination occurring before 1850 in southwestern Germany, differs from the record published for Switzerland mainly due to the mining activity in Black Forest. Taken together, the results show that peat cores from ombrotrophic bogs can yield accurate records of atmospheric Pb deposition, provided that the cores are carefully collected, handled, prepared, and analysed using appropriate methods

Elemental and isotopic analysis of americium in non-separated spent fuel using high resolution ICP-OES and sector field ICP-MS

As there are no certified reference materials, accurate, straightforward analytical procedures for the determination of americium (Am) in non-separated spent fuels employing high resolution ICP-OES and sector field (SF-)ICP-MS were developed and cross-validated. One spent (Th,Pu)O2 fuel and two U/Pu-based spent fuels representing different chemical and isotopic compositions were analysed for their Am content. Even though the lowest limit of detection (0.07 µg kg-1) was obtained at 283.226 nm, the ICP-OES signal at 408.929 nm provided the most reliable performance for the analysis of spent fuel among the six investigated Am emission wavelengths. A massive spectral interference from Th omitted the use of the 283.226 nm emission line for Am analysis of the (Th,Pu)O2 fuel, while other potential interferences from plutonium (Pu) and neptunium (Np) could be excluded for all tested Am wavelengths. Employing ICP-OES, both external calibration and standard addition yielded comparable Am concentrations. Calibration of the SF-ICP-MS response for Am was accomplished using both 232Th and 238U signals as well as applying the related mass bias. This calibration methodology that is frequently used in absence of an Am stock standard solution, was tested against a home-made 241Am stock standard solution underpinning the validity of this calibration approach. Sector field ICP-MS analysis essentially confirmed the Am concentrations obtained using ICP-OES in the three spent fuel solutions with mean values overlapping within their standard deviations. Considering isotopes of other actinides such as Pu and curium (Cm), the Am isotopic abundance (241Am, 242Am, 243Am) was established in two non-separated fuel solutions comparing well with model calculations based on the ORIGEN-2 code.JRC.E.5-Nuclear chemistr

Challenges in the quality assurance of elemental and isotopic analyses in the nuclear domain benefitting from high resolution ICP-OES and sector field ICP-MS

Accurate analytical data reinforces fundamentally the meaningfulness of nuclear fuel performance assessments and nuclear waste characterization. Regularly lacking matrix-matched certified reference materials, quality assurance of elemental and isotopic analysis of nuclear materials remains a challenging endeavour. In this context, this review highlights various dedicated experimental approaches envisaged at the European Commission – Joint Research Centre – Institute for Transuranium Elements to overcome this limitation, mainly focussing on the use of high resolution-inductively coupled plasma-optical emission spectrometry (HR-ICP-OES) and sector field-inductively coupled plasma-mass spectrometry (SF-ICP-MS). However, also - and -spectrometry are included here to help characterise extensively the investigated actinide solutions for their actual concentration, thinkable impurities and isotopic purity.JRC.E.5-Nuclear chemistr

A new method for the determination of plutonium and americium using high pressure microwave digestion and alpha-spectrometry or ICP-SMS

Plutonium and americium are radionuclides particularly difficult to measure in environmental samples because they are α-emitters and therefore necessitate a careful separation before any measurement, either using radiometric methods or ICP-SMS. Recent developments in extraction chromatography resins such as Eichrom® TRU and TEVA have resolved many of the analytical problems but drawbacks such as low recovery and spectral interferences still occasionally occur. Here, we report on the use of the new Eichrom® DGA resin in association with TEVA resin and high pressure microwave acid leaching for the sequential determination of plutonium and americium in environmental samples. The method results in average recoveries of 83±15% for plutonium and 73±22% for americium (n=60), and a less than 10% deviation from reference values of four IAEA reference materials and three samples from intercomparisons exercises. The method is also suitable for measuring 239Pu in water samples at the μBq/l level, if ICP-SMS is used for the measuremen