Glycosaminoglycan profiles of repair tissue formed following autologous chondrocyte implantation differ from control cartilage

Currently, autologous chondrocyte implantation (ACI) is the most commonly used cell-based therapy for the treatment of isolated femoral condyle lesions of the knee. A small number of centres performing ACI have reported encouraging long-term clinical results, but there is currently a lack of quantitative and qualitative biochemical data regarding the nature of the repair tissue. Glycosaminoglycan (GAG) structure influences physiological function and is likely to be important in the long-term stability of the repair tissue. The objective of this study was to use fluorophore-assisted carbohydrate electrophoresis (FACE) to both quantitatively and qualitatively analyse the GAG composition of repair tissue biopsies and compare them with age-matched cadaveric controls. We used immunohistochemistry to provide a baseline reference for comparison. Biopsies were taken from eight patients (22 to 52 years old) 1 year after ACI treatment and from four cadavers (20 to 50 years old). FACE quantitatively profiled the GAGs in as little as 5 μg of cartilage. The pattern and intensity of immunostaining were generally comparable with the data obtained with FACE. In the ACI repair tissue, there was a twofold reduction in chondroitin sulphate and keratan sulphate compared with age-matched control cartilage. By contrast, there was an increase in hyaluronan with significantly shorter chondroitin sulphate chains and less chondroitin 6-sulphate in repair tissue than control cartilage. The composition of the repair tissue thus is not identical to mature articular cartilage

Emotional Intelligence as Assessed by Situational Judgment and Emotion Recognition Tests: Building the Nomological Net

Recent research on emotion recognition ability (ERA) suggests that the capacity to process emotional information may differ for disparate emotions. However, little research has examined whether this findings holds for emotional understanding and emotion management, as well as emotion recognition. Moreover, little research has examined whether the abilities to recognize emotions, understand emotions, and manage emotions form a distinct emotional intelligence (EI) construct that is independent from traditional cognitive ability factors. The current study addressed these issues. Participants (N=118) completed two ERA measures, two situational judgment tests assessing emotional understanding and emotion management, and three cognitive ability tests. Exploratory and confirmatory factor analyses of both the understanding and management item parcels showed that a three-factor model relating to fear, sadness, and anger content was a better fit than a one-factor model, supporting an emotion-specific view of EI. In addition, an EI factor composed of emotion recognition, emotional understanding, and emotion management was distinct from a cognitive ability factor composed of a matrices task, general knowledge test, and reading comprehension task. Results are discussed in terms of their potential implications for theory and practice, as well as the integration of EI research with known models of cognitive ability

Multiwavelength monitoring of a very active dwarf nova AX J1549.8-5416 with an unusually high duty cycle

We present the results of our analysis of new optical, ultraviolet (UV) and X-ray observations of a highly variable source − AX J1549.8−5416. Both the detection of several fast rise, exponential decay outbursts in the optical light curve and the lack of He II emission lines in the optical spectra suggest AX J1549.8−5416 is a cataclysmic variable of the dwarf nova (DN) type. The multiwavelength analysis of three mini-outbursts and one normal outburst represent one of the most complete multiwavelength studies of a DN and help to refine the relationship between the X-ray, UV and optical emission in this system. We find that the UV emission is delayed with respect to the optical by 1.0–5.4 d during the rising phase of the outburst. The X-ray emission is suppressed during the peak of the optical outburst and recovers during the end of the outburst. From our analysis of archival Swift, Chandra and XMM–Newton observations of AX J1549.8−5416, we estimate this DN has a high duty cycle (∼50 per cent), suggesting a quiescent X-ray luminosity larger than 1032 erg/s. We also find the X-ray and UV flux are roughly anticorrelated. Furthermore, we find that, at low X-ray fluxes, the X-ray spectrum is well described by a single temperature thermal plasma model, while at high X-ray fluxes, an isobaric cooling flow model also works. We find that the maximum temperature of the plasma in quiescence is significantly higher than that in outburst.Instituto de Astrofísica de La Plat

Multiwavelength monitoring of a very active dwarf nova AX J1549.8-5416 with an unusually high duty cycle

We present the results of our analysis of new optical, ultraviolet (UV) and X-ray observations of a highly variable source − AX J1549.8−5416. Both the detection of several fast rise, exponential decay outbursts in the optical light curve and the lack of He II emission lines in the optical spectra suggest AX J1549.8−5416 is a cataclysmic variable of the dwarf nova (DN) type. The multiwavelength analysis of three mini-outbursts and one normal outburst represent one of the most complete multiwavelength studies of a DN and help to refine the relationship between the X-ray, UV and optical emission in this system. We find that the UV emission is delayed with respect to the optical by 1.0–5.4 d during the rising phase of the outburst. The X-ray emission is suppressed during the peak of the optical outburst and recovers during the end of the outburst. From our analysis of archival Swift, Chandra and XMM–Newton observations of AX J1549.8−5416, we estimate this DN has a high duty cycle (∼50 per cent), suggesting a quiescent X-ray luminosity larger than 1032 erg/s. We also find the X-ray and UV flux are roughly anticorrelated. Furthermore, we find that, at low X-ray fluxes, the X-ray spectrum is well described by a single temperature thermal plasma model, while at high X-ray fluxes, an isobaric cooling flow model also works. We find that the maximum temperature of the plasma in quiescence is significantly higher than that in outburst.Instituto de Astrofísica de La Plat

The role played by invasive species in interactions with endangered and threatened species in the United States: a systematic review

Invasive species are considered to be a leading cause of the decline of threatened species. However, this view has been disputed because much of the evidence base is anecdotal. This systematic review, through an extensive, repeatable search using agreed selection criteria, examined the available scientific evidence on invasive species’ interactions with the 1363 endangered and threatened species protected under the United States Endangered Species Act (ESA). The review found scientific evidence available for 116 endangered or threatened species (8.5% of the ESA list). Of these, 85 species (6.2%) were reported as being negatively impacted by invasive species: 39 located on the continental US and 39 on islands, with seven marine species. The relative percentages of species impacted differed according to location: 4.3% (n = 906) on the continental US, 9.3% (n = 420) on islands. It was found that predation by invasive vertebrates on birds on islands and competition between invasive plants and endangered or threatened plants on the mainland were the main mechanisms of impact. The results of this study contrast markedly with a previous study which found that 49% of imperilled species in the United States were threatened by invasive species. Further research is essential in order to evaluate the impact of invasive species on imperilled species on the ESA list; this would help to reduce the high degree of uncertainty regarding the threat of invasive species due to the lack of empirical information

A comparative analysis of algorithms for somatic SNV detection in cancer

Motivation: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer–normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer–normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm. Results: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates.Nicola D. Roberts, R. Daniel Kortschak, Wendy T. Parker, Andreas W. Schreiber, Susan Branford, Hamish S. Scott, Garique Glonek and David L. Adelso

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship

BACKGROUND AND OBJECTIVE: Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). DATA SOURCES: We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. RESULTS: Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. CONCLUSIONS AND IMPLICATIONS: The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities. REVIEW REGISTRATION: The review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266

Temporal, Spatial, and Genomic Analyses of Enterobacteriaceae Clinical Antimicrobial Resistance in Companion Animals Reveals Phenotypes and Genotypes of One Health Concern

BackgroundAntimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data.ObjectivesWe aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories.MethodsWe summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites.ResultsEscherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7–70.0) and cats (90.5%, CI 89.8–91.3). Multi-drug resistance was reported in 14.1% (CI 13.5–14.8) of canine and 12.0% (CI 11.1–12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2–3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum β-lactamase gene blaCTX–M–15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals.ConclusionsLinking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.</sec

SOCS3 Is a Critical Physiological Negative Regulator of G-CSF Signaling and Emergency Granulopoiesis

AbstractTo determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the regulation of hematopoietic growth factor signaling generally, and of G-CSF-induced cellular responses specifically, we created mice in which the Socs3 gene was deleted in all hematopoietic cells. Although normal until young adulthood, these mice then developed neutrophilia and a spectrum of inflammatory pathologies. When stimulated with G-CSF in vitro, SOCS3-deficient cells of the neutrophilic granulocyte lineage exhibited prolonged STAT3 activation and enhanced cellular responses to G-CSF, including an increase in cloning frequency, survival, and proliferative capacity. Consistent with the in vitro findings, mutant mice injected with G-CSF displayed enhanced neutrophilia, progenitor cell mobilization, and splenomegaly, but unexpectedly also developed inflammatory neutrophil infiltration into multiple tissues and consequent hind-leg paresis. We conclude that SOCS3 is a key negative regulator of G-CSF signaling in myeloid cells and that this is of particular significance during G-CSF-driven emergency granulopoiesis