Limits on the ultra-bright Fast Radio Burst population from the CHIME Pathfinder

We present results from a new incoherent-beam Fast Radio Burst (FRB) search on the Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder. Its large instantaneous field of view (FoV) and relative thermal insensitivity allow us to probe the ultra-bright tail of the FRB distribution, and to test a recent claim that this distribution's slope, $\alpha\equiv-\frac{\partial \log N}{\partial \log S}$, is quite small. A 256-input incoherent beamformer was deployed on the CHIME Pathfinder for this purpose. If the FRB distribution were described by a single power-law with $\alpha=0.7$, we would expect an FRB detection every few days, making this the fastest survey on sky at present. We collected 1268 hours of data, amounting to one of the largest exposures of any FRB survey, with over 2.4\,$\times$\,10$^5$\,deg$^2$\,hrs. Having seen no bursts, we have constrained the rate of extremely bright events to $<\!13$\,sky$^{-1}$\,day$^{-1}$ above $\sim$\,220$\sqrt{(\tau/\rm ms)}$ Jy\,ms for $\tau$ between 1.3 and 100\,ms, at 400--800\,MHz. The non-detection also allows us to rule out $\alpha\lesssim0.9$ with 95$\%$ confidence, after marginalizing over uncertainties in the GBT rate at 700--900\,MHz, though we show that for a cosmological population and a large dynamic range in flux density, $\alpha$ is brightness-dependent. Since FRBs now extend to large enough distances that non-Euclidean effects are significant, there is still expected to be a dearth of faint events and relative excess of bright events. Nevertheless we have constrained the allowed number of ultra-intense FRBs. While this does not have significant implications for deeper, large-FoV surveys like full CHIME and APERTIF, it does have important consequences for other wide-field, small dish experiments

Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion

The outcome of ring expansion reactions based on amino/hydroxyacid side chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and β-ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a Density Functional Theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam- and β-ketoester-based ring expansion reactions

Association Between Pharmacokinetics of Adalimumab and Mucosal Healing in Patients With Inflammatory Bowel Diseases

International audienceBACKGROUND & AIMS:Little is known about the association between pharmacokinetic features of adalimumab and mucosal healing in patients with inflammatory bowel disease (IBD).METHODS:We conducted a cross-sectional study of 40 patients with Crohn's disease (CD) or ulcerative colitis (UC) who received adalimumab maintenance therapy and underwent endoscopic evaluation of disease activity and pharmacokinetic analysis (measurements of trough levels and antibodies against adalimumab). Patients in clinical remission were identified based on CD activity index scores less than 150 or Mayo scores less than 3 (for those with UC). Patients with mucosal healing were identified based on Mayo endoscopic scores less than 2 (for UC) or the disappearance of all ulcerations (for CD).RESULTS:The median trough level of adalimumab was higher in patients in clinical remission (6.02 μg/mL) than in patients with active disease (3.2 μg/mL; P = .012). Trough levels of adalimumab were also higher in patients with mucosal healing (6.5 μg/mL) than in patients without (4.2 μg/mL;  P  <  .005). These results did not vary with type of IBD. On multivariate analysis, trough levels of adalimumab (relative risk, 0.62; 95% confidence interval, 0.40-0.94; P = .026) and duration of adalimumab treatment (relative risk, 0.82; 95% confidence interval, 0.68-0.97; P = .026) were associated independently with healing mucosa. An absence of mucosal healing was associated with trough levels of adalimumab less than 4.9 μg/mL (likelihood ratio, 4.3; sensitivity, 66%; specificity, 85%).CONCLUSIONS:Trough levels of adalimumab are significantly higher in IBD patients who are in clinical remission and in those with mucosal healing. Detection of antibodies against adalimumab predicts a lack of mucosal healing

Therapeutic Drug Monitoring of Infliximab and Mucosal Healing in Inflammatory Bowel Disease

International audienceBackgroundData on the value of therapeutic drug monitoring of infliximab (IFX) to predict mucosal healing (MH) in inflammatory bowel diseases (IBD) are scarce.MethodsAll consecutive patients with IBD receiving ongoing IFX (5 mg/kg) treatment and developing secondary failure to IFX were enrolled in a prospective study between June 2010 and May 2011. IFX trough levels, antibodies to IFX concentrations, C-reactive protein levels, and fecal calprotectin were measured before IFX optimization and at week 8. A proctosigmoidoscopy was performed on the day of first IFX optimization and at week 8 in all patients with ulcerative colitis (UC). MH was defined by fecal calprotectin 0.5 μg/mL was associated with MH (sensitivity [se], 0.88; specificity [sp], 0.77; P = 0.0001, area under the receiver operating characteristic curve, 0.89). On multivariate analysis, the only factor associated with MH after IFX optimization was a delta IFX >0.5 µg/mL (likelihood ratio = 2.02; 95% confidence interval, 1.01–4.08; P = 0.048) in patients with IBD.ConclusionsTherapeutic drug monitoring of IFX strongly predicts the likelihood of achieving MH following IFX dose intensification in both CD and UC