Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus)

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes

Computational design of accelerated life testing applied to frozen green beans

Three different accelerated life tests (ALT) were designed by computer simulation to investigate their practical applicability to quantify kinetics of quality loss in frozen stored foods. Heat transfer and quality degradation inside a green bean were simulated, using a spectral finite element method (SFEM), to develop pseudo-experimental data. Temperature fluctuations inside a refrigerator were simulated, by a piecewise linear stochastic differential equation, and integrated into the SFEM program. Thereafter, the simulated data was treated by non-linear regression analysis to estimate the kinetic parameters. The different ALT tests were then compared in terms of precision and accuracy. This study shows that temperature fluctuations, inside a refrigerator, influence the accuracy of the kinetic estimates, and if the temperature spectrum is used to derive kinetic estimates, it is possible to apply accurately ALT methodologies to frozen foods

Search for the decay K+→π+ννˉK^+\to \pi^+ \nu \bar\nu in the momentum region Pπ<195 MeV/cP_\pi < 195 {\rm ~MeV/c}

We have searched for the decay $K^+ \to \pi^+ \nu \bar\nu$ in the kinematic region with pion momentum below the $K^+ \to \pi^+ \pi^0$ peak. One event was observed, consistent with the background estimate of $0.73\pm 0.18$. This implies an upper limit on $B(K^+ \to \pi^+ \nu \bar\nu)< 4.2\times 10^{-9}$ (90% C.L.), consistent with the recently measured branching ratio of $(1.57^{+1.75}_{-0.82}) \times 10^{-10}$, obtained using the standard model spectrum and the kinematic region above the $K^+ \to \pi^+ \pi^0$ peak. The same data were used to search for $K^+ \to \pi^+ X^0$, where $X^0$ is a weakly interacting neutral particle or system of particles with $150 < M_{X^0} < 250 {\rm ~MeV/c^2}$.Comment: 4 pages, 2 figure

Mechanical Behavior and Microstructural Development of Low-Carbon Steel and Microcomposite Steel Reinforcement Bars Deformed under Quasi-Static and Dynamic Shear Loading

Reinforcement bars of microcomposite (MC) steel, composed of lath martensite and minor amounts of retained austenite, possess improved strength and corrosion characteristics over low-carbon (LC) steel rebar; however, their performance under shear loading has not previously been investigated at the microstructural level. In this study, LC and MC steel cylinders were compression tested, and specimens machined into a forced-shear geometry were subjected to quasi-static and dynamic shear loading to determine their shear behavior as a function of the strain and strain rate. The as-received and sheared microstructures were examined using optical microscopy (OM), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). Higher-resolution microstructural examinations were performed using transmission electron microscopy (TEM). The influence of the starting microstructure on the shear behavior was found to depend strongly on the strain rate; the MC steel exhibited not only greater strain-rate sensitivity than the LC steel but also a greater resistance to shear localization with load. In both steels, despite differences in the starting microstructure, post-mortem observations were consistent with a continuous mechanism operating within adiabatic shear bands (ASBs), in which subgrains rotated into highly misoriented grains containing a high density of dislocations

Becoming a special educator – Finnish and Swedish students' views of their future profession

Peer reviewe

Further search for the decay K+→π+ννˉK^+ \to \pi^+ \nu \bar \nu in the momentum region P < 195 MeV/c

We report the results of a search for the decay $K^+ \to \pi^+ \nu \bar \nu$ in the kinematic region with $\pi^+$ momentum $140 < P < 195$ MeV/c using the data collected by the E787 experiment at BNL. No events were observed. When combined with our previous search in this region, one candidate event with an expected background of $1.22 \pm 0.24$ events results in a 90% C.L. upper limit of $2.2 \times 10^{-9}$ on the branching ratio of $K^+ \to \pi^+ \nu \bar \nu$. We also report improved limits on the rates of $K^+ \to \pi^+ X^0$ and $K^+ \to \pi^+ X^1 X^2$ where $X^0, X^1, X^2$ are hypothetical, massless, long-lived neutral particles.Comment: 5 pages, 3 figures, Accepted for publication in Phys. Rev.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

Background Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils. Methods We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40–80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015. Inclusion criteria for this analysis were SPIROMICS baseline visit data with complete blood cell counts and, in a subset, acceptable sputum counts. We stratified patients on the basis of blood and sputum eosinophil concentrations and compared their demographic characteristics, as well as results from questionnaires, clinical assessments, and quantitative CT (QCT). We also analysed whether blood eosinophil concentrations reliably predicted sputum eosinophil concentrations. This study is registered with ClinicalTrials.gov (NCT01969344). Findings Of the 2737 patients recruited to SPIROMICS, 2499 patients were smokers and had available blood counts, and so were stratified by mean blood eosinophil count: 1262 patients with low (&lt;200 cells per μL) and 1237 with high (≥200 cells per μL) blood eosinophil counts. 827 patients were eligible for stratification by mean sputum eosinophil percentage: 656 with low (&lt;1·25%) and 171 with high (≥1·25%) sputum eosinophil percentages. The high sputum eosinophil group had significantly lower median FEV1 percentage predicted than the low sputum eosinophil group both before (65·7% [IQR 51·8–81·3] vs 75·7% [59·3–90·2], p&lt;0·0001) and after (77·3% [63·1–88·5] vs 82·9% [67·8–95·9], p=0·001) bronchodilation. QCT density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than the low sputum eosinophil group. Exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (p=0·002). FEV1 percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups. The high blood eosinophil group had slightly increased airway wall thickness (0·02 mm difference, p=0·032), higher St George Respiratory Questionnaire symptom scores (p=0·037), and increased wheezing (p=0·018), but no evidence of an association with COPD exacerbations (p=0·35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, Body-mass index, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage. Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0·64, p&lt;0·0001), but with a high false-discovery rate of 72%. Interpretation In a large, well characterised cohort of former and current smoking patients with a broad range of COPD severity, high concentrations of sputum eosinophils were a better biomarker than high concentrations of blood eosinophils to identify a patient subgroup with more severe disease, more frequent exacerbations, and increased emphysema by QCT. Blood eosinophils alone were not a reliable biomarker for COPD severity or exacerbations, or for sputum eosinophils. Clinical trials targeting eosinophilic inflammation in COPD should consider assessing sputum eosinophils. Funding National Institutes of Health, and National Heart, Lung, and Blood Institute