Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis

Background: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. Method: Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. Results: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). Conclusions: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. Trial registration: ClinicalTrials.Gov Identifier: NCT01383954. Registered June 22, 2011

Antimicrobial resistance monitoring and surveillance in the meat chain: A report from five countries in the European Union and European Economic Area

Background The emergence of antimicrobial resistance (AMR) in zoonotic foodborne pathogens (Salmonella, Campylobacter) and indicator microorganisms (E. coli, enterococci) is a major public health risk. Zoonotic bacteria, resistant to antimicrobials, are of special concern because they might compromise the effective treatment of infections in humans. Scope and approach In this review, the AMR monitoring and surveillance programmes in five selected countries within European Union (EU) and European Economic Area (EEA) are described. The sampling schemes, susceptibility testing for AMR identification, clinical breakpoints (clinical resistance) and epidemiological cut-off values (microbiological resistance) were considered to reflect on the most important variations between and within food-producing animal species, between countries, and to identify the most effective approach to tackle and manage the antimicrobial resistance in the food chain. Key findings and conclusions The science-based monitoring of AMR should encompass the whole food chain, supported with public health surveillance and should be conducted in accordance with ‘Zoonoses Directive’ (99/2003/EC). Such approach encompasses the integrated AMR monitoring in food animals, food and humans in the whole food (meat) chain continuum, e.g. pre-harvest (on-farm), harvest (in abattoir) and post-harvest (at retail). The information on AMR in critically important antimicrobials (CIA) for human medicine should be of particular importance

The VIMOS VLT Deep Survey: Evolution of the non-linear galaxy bias up to z=1.5

We present the first measurements of the Probability Distribution Function (PDF) of galaxy fluctuations in the VIMOS-VLT Deep Survey (VVDS) cone, covering 0.4x0.4 deg between 0.4<z<1.5. The second moment of the PDF, i.e. the rms fluctuations of the galaxy density field, is with good approximation constant over the full redshift baseline investigated: we find that, in redshift space, sigma_8 for galaxies brighter than M=-20+5log h has a mean value of 0.94\pm0.07 in the redshift interval 0.7<z<1.5. The third moment, i.e. the skewness, increases with cosmic time: we find that the probability of having underdense regions is greater at z~0.7 than it was at z~1.5. By comparing the PDF of galaxy density contrasts with the theoretically predicted PDF of mass fluctuations we infer the redshift-, density-, and scale-dependence of the biasing function b(z, \delta, R) between galaxy and matter overdensities up to redshift z=1.5. Our results can be summarized as follows: i) the galaxy bias is an increasing function of redshift: evolution is marginal up to z~0.8 and more pronounced for z>0.8; ii) the formation of bright galaxies is inhibited below a characteristic mass-overdensity threshold whose amplitude increases with redshift and luminosity; iii) the biasing function is non linear in all the redshift bins investigated with non-linear effects of the order of a few to 10% on scales >5Mpc.Comment: 30 pages, 17 figs, Accepted by A&

The density and peculiar velocity fields of nearby galaxies

We review the quantitative science that can be and has been done with redshift and peculiar velocity surveys of galaxies in the nearby universe. After a brief background setting the cosmological context for this work, the first part of this review focuses on redshift surveys. The practical issues of how redshift surveys are carried out, and how one turns a distribution of galaxies into a smoothed density field, are discussed. Then follows a description of major redshift surveys that have been done, and the local cosmography out to 8,000 km/s that they have mapped. We then discuss in some detail the various quantitative cosmological tests that can be carried out with redshift data. The second half of this review concentrates on peculiar velocity studies, beginning with a thorough review of existing techniques. After discussing the various biases which plague peculiar velocity work, we survey quantitative analyses done with peculiar velocity surveys alone, and finally with the combination of data from both redshift and peculiar velocity surveys. The data presented rule out the standard Cold Dark Matter model, although several variants of Cold Dark Matter with more power on large scales fare better. All the data are consistent with the hypothesis that the initial density field had a Gaussian distribution, although one cannot rule out broad classes of non-Gaussian models. Comparison of the peculiar velocity and density fields constrains the Cosmological Density Parameter. The results here are consistent with a flat universe with mild biasing of the galaxies relative to dark matter, although open universe models are by no means ruled out.Comment: In press, Physics Reports. 153 pages. gzip'ed postscript of text plus 20 embedded figures. Also available via anonymous ftp at ftp://eku.ias.edu/pub/strauss/review/physrep.p

Testable anthropic predictions for dark energy

In the context of models where the dark energy density \rD is a random variable, anthropic selection effects may explain both the "old" cosmological constant problem and the "time coincidence". We argue that this type of solution to both cosmological constant problems entails a number of definite predictions, which can be checked against upcoming observations. In particular, in models where the dark energy density is a discrete variable, or where it is a continuous variable due to the potential energy of a single scalar field, the anthropic approach predicts that the dark energy equation of state is $p_D=-\rho_D$ with a very high accuracy. It is also predicted that the dark energy density is greater than the currently favored value $\Omega_D\approx 0.7$. Another prediction, which may be testable with an improved understanding of galactic properties, is that the conditions for civilizations to emerge arise mostly in galaxies completing their formation at low redshift, $z\approx 1$. Finally, there is a prediction which may not be easy to test observationally: our part of the universe is going to recollapse eventually. However, the simplest models predict that it will take more than a trillion years of accelerated expansion before this happens.Comment: 21 pages, 3 figures. Two errors in the published version are pointed out and corrected. Further typos correcte

Local and global environmental effects on galaxies and active galactic nuclei

We study the properties of SDSS galaxies with and without AGN detection as a function of the local and global environment measured via the local density, the mass of the galaxy host group (parameterised by the group luminosity) and distance to massive clusters. Our results can be divided in two main subjects, the environments of galaxies and their relation to the assembly of their host haloes, and the environments of AGN. (i) For the full SDSS sample, we find indications that the local galaxy density is the most efficient parameter to separate galaxy populations, but we also find that galaxies at fixed local density show some remaining variation of their properties as a function of the distance to the nearest cluster of galaxies (in a range of 0 to 10 cluster virial radii). These differences seem to become less significant if the galaxy samples are additionally constrained to be hosted by groups of similar total luminosity. (ii) In AGN host galaxies, the morphology-density relation is much less noticeable when compared to the behaviour of the full SDSS sample. In order to interpret this result we analyse control samples constructed using galaxies with no detected AGN activity with matching distributions of redshifts, stellar masses, r-band luminosities, g-r colours, concentrations, local densities, host group luminosities, and fractions of central and satellite galaxies. The control samples also show a similar small dependence on the local density indicating an influence from the AGN selection, but their colours are slightly bluer compared to the AGN hosts regardless of local density. Furthermore, even when the local density is held fixed at intermediate or high values, and the distance to the closest cluster of galaxies is allowed to vary, AGN control galaxies away from clusters tend to be bluer than the AGN hosts. (ABRIDGED)Comment: 18 pages, 7 figures, MNRAS, in pres

Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana

Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent. This indicates that the resistance phenotype is related to loss of drug binding. Comparing sequences of the parasites’ genomes revealed a plethora of single nucleotide polymorphisms that distinguish wild-type and resistant cells, but only one of these was found to be homozygous and associated with a gene encoding an enzyme in the sterol biosynthetic pathway, sterol 14α-demethylase (CYP51). The mutation, N176I, is found outside of the enzyme’s active site, consistent with the fact that the resistant line continues to produce the enzyme’s product. Expression of wild-type sterol 14α-demethylase in the resistant cells caused reversion to drug sensitivity and a restoration of ergosterol synthesis, showing that the mutation is indeed responsible for resistance. The amphotericin B resistant parasites become hypersensitive to pentamidine and also agents that induce oxidative stress. This work reveals the power of combining polyomics approaches, to discover the mechanism underlying drug resistance as well as offering novel insights into the selection of resistance to amphotericin B itself

Individuals with chronic low back pain have greater difficulty in engaging in positive lifestyle behaviours than those without back pain: An assessment of health literacy

Background: Despite the large volume of research dedicated to understanding chronic low back pain (CLBP), patient outcomes remain modest while healthcare costs continue to rise, creating a major public health burden. Health literacy - the ability to seek, understand and utilise health information - has been identified as an important factor in the course of other chronic conditions and may be important in the aetiology of CLBP. Many of the currently available health literacy measurement tools are limited since they measure narrow aspects of health literacy. The Health Literacy Measurement Scale (HeLMS) was developed recently to measure broader elements of health literacy. The aim of this study was to measure broad elements of health literacy among individuals with CLBP and without LBP using the HeLMS.Methods: Thirty-six community-dwelling adults with CLBP and 44 with no history of LBP responded to the HeLMS. Individuals were recruited as part of a larger community-based spinal health study in Western Australia. Scores for the eight domains of the HeLMS as well as individual item responses were compared between the groups.Results: HeLMS scores were similar between individuals with and without CLBP for seven of the eight health literacy domains (p &gt; 0.05). However, compared to individuals with no history of LBP, those with CLBP had a significantly lower score in the domain &lsquo;Patient attitudes towards their health&rsquo; (mean difference [95% CI]: 0.46 [0.11- 0.82]) and significantly lower scores for each of the individual items within this domain (p &lt; 0.05). Moderate effect sizes ranged from d = 0.47-0.65.Conclusions: Although no differences were identified in HeLMS scores between the groups for seven of the health literacy domains, adults with CLBP reported greater difficulty in engaging in general positive health behaviours. This aspect of health literacy suggests that self-management support initiatives may benefit individuals with CLBP.<br /