Molecular diversity within clonal complex 22 methicillin-resistant Staphylococcus aureus encoding Panton–Valentine leukocidin in England and Wales

AbstractPanton–Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) that are multi-locus sequence type clonal complex 22 (CC22) comprise a significant public health problem in the UK. In the present study we sought to determine the genetic diversity, and the respective patient demographics, among 47 PVL-MRSA with a CC22 pulsotype that occurred sporadically or in clusters in community and healthcare settings in eight of nine geographic regions in England and Wales between January 2005 and September 2007. Patient demographics and disease presentations were typical for PVL-S. aureus infections (mostly skin and soft tissue infections in individuals <40 years old); one patient with community-acquired pneumonia died. Although the isolates were closely genotypically related by spa typing and pulsed field gel electrophoresis, at least two variant groups were suggested. PCR detections demonstrated that the majority of the CC22 PVL-MRSA identified (n = 42; 89%) harboured SCCmecIVc, three had SCCmecIVd, one had SCCmecIV but was non-subtypeable, and one isolate harboured SCCmecV. At least three different PVL-encoding phages were detected: ΦPVL, Φ108PVL and an unidentified icosahedral phage. Agar dilution MIC determinations showed that the CC22 PVL-MRSA identified were typically resistant to gentamicin and trimethoprim (43 of 47 isolates) and ciprofloxacin resistance was also noted in six isolates. In conclusion, the CC22 PVL-MRSA tested were geographically disseminated but highly genetically related. The observed variances in acquired elements (most notably SCCmec and PVL-encoding phages) suggested that CC22 PVL-MRSA in England and Wales have evolved on multiple occasions

An Ecological Basis for Ecosystem Management

This report was prepared by the Southwestern Regional Ecosystem Management Study Team composed of management and research biologists. The USDA Forest Service Southwestern Regions Regional Forester, Larry Henson, and the Rocky Mountain Forest and Range Experiment Station Director, Denver Burns, chartered this team to recommend an ecological basis for ecosystem management. This report is not intended to provide details on all aspects of ecosystem management; it simply provides information and makes recommendations for an ecological basis for ecosystem management. The report is not a decision document. It does not allocate resources on public lands nor does it make recommendations to that effect. The report of this Study Team may be relied upon as input in processes initiated under the National Environmental Policy Act (NEPA), National Forest Management Act (NFMA), Endangered Species Act (ESA), Administrative Procedures Act (APA), and other applicable laws. The information contained in this report is general in nature, rather than site specific. Implementation of ecosystem management and allocation of resources on Forest Service administered lands is the responsibility of the National Forest System in partnership with Forest Service Research and State and Private Forestry. Implementation is done through Forest and project plans that are subject to the NEPA process of disclosing the effects of proposed actions and affording the opportunity for public comment. The Southwestern Region follows a planning process for projects called Integrated Resource Management (IRM). The opinions expressed by the authors do not necessarily represent the policy or position of the U.S. Department of Agriculture, the Forest Service, The Nature Conservancy, or the Arizona Game and Fish Department. The Study Team acknowledges the valuable input of more than 50 individuals from various agencies, universities, professional organizations, and other groups who provided thoughtful comments of an earlier draft of this document. Some of their comments are included in Appendix 3

Itinerant electron metamagnetism in LaCo9_9Si4_4

The strongly exchange enhanced Pauli paramagnet LaCo$_9$Si$_4$ is found to exhibit an itinerant metamagnetic phase transition with indications for metamagnetic quantum criticality. Our investigation comprises magnetic, specific heat, and NMR measurements as well as ab-initio electronic structure calculations. The critical field is about 3.5 T for $H||c$ and 6 T for $H\bot c$, which is the lowest value ever found for rare earth intermetallic compounds. In the ferromagnetic state there appears a moment of about 0.2 $\mu_B$/Co at the $16k$ Co-sites, but sigificantly smaller moments at the 4d and $16l$ Co-sites.Comment: 11 pages, 5 figures, PRB Rapid Communication, in prin

Targeting the Ataxia Telangiectasia Mutated-null Phenotype in Chronic Lymphocytic Leukemia with Pro-oxidants

Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumours with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance

A validation study of the ICECAP‑O in informal carers of people with dementia from eight European Countries

Purpose The pressure on healthcare budgets remains high, partially due to the ageing population. Economic evaluation can be a helpful tool to inform resource allocation in publicly financed systems. Such evaluations frequently use health-related outcome measures. However, in areas such as care of older people, improving health outcomes is not necessarily the main focus of care interventions and broader outcome measures, including outcomes for those providing informal care, may be preferred when evaluating such interventions. This paper validates a recently introduced well-being measure, the ICECAP-O, in a population of informal carers for people with dementia from eight European countries. Methods Convergent and discriminant validity tests were performed to validate the ICECAP-O using data obtained in a sample of 451 respondents from Germany, Ireland, Italy, the Netherlands, Norway, Portugal, Sweden and the UK. These respondents completed a number of standardized questionnaires within the framework of the Actifcare project. Results The ICECAP-O performed well among informal carers, in terms of both convergent and discriminant validity. In the multivariate analysis, it was found to be significantly associated with the age of the person with dementia, EQ-5D-5L health problem index of the person with dementia, carer–patient relationship, care recipient CDR, carer LSNS Score, the PAI score, and Perseverance Time. Conclusion The ICECAP-O appears to be a valid measure of well-being in informal carers for people with dementia. The ICECAP-O may therefore be useful as an outcome measure in economic evaluations of interventions aimed at such informal carers, when these aim to improve well-being beyond health

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

High-Accuracy X-Ray Diffraction Analysis of Phase Evolution Sequence During Devitrification of Cu50Zr50 Metallic Glass

Real-time high-energy X-ray diffraction (HEXRD) was used to investigate the crystallization kinetics and phase selection sequence for constant-heating-rate devitrification of fully amorphous Cu50Zr50, using heating rates from 10 K/min to 60 K/min (10 °C/min to 60 °C/min). In situ HEXRD patterns were obtained by the constant-rate heating of melt-spun ribbons under synchrotron radiation. High-accuracy phase identification and quantitative assessment of phase fraction evolution though the duration of the observed transformations were performed using a Rietveld refinement method. Results for 10 K/min (10 °C/min) heating show the apparent simultaneous formation of three phases, orthorhombic Cu10Zr7, tetragonal CuZr2 (C11b), and cubic CuZr (B2), at 706 K (433 °C), followed immediately by the dissolution of the CuZr (B2) phase upon continued heating to 789 K (516 °C). Continued heating results in reprecipitation of the CuZr (B2) phase at 1002 K (729 °C), with the material transforming completely to CuZr (B2) by 1045 K (772 °C). The Cu5Zr8 phase, previously reported to be a devitrification product in C50Zr50, was not observed in the present study

The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer

Background: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. Methods: The toxicity of aspirin and aspirin derivatives to OC and a colorectal cancer (CRC) cell line were investigated in the presence and absence of platins. Results: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 CRC cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. Conclusion: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins