Production of D∗+(2010)D^{*+}(2010) mesons by high energy neutrinos from the Tevatron

Charged vector $D^{*+}(2010)$ meson production is studied in a high energy neutrino bubble chamber experiment with mean neutrino energy of 141 GeV. The $D^{*+}$ are produced in $(5.6 \pm 1.8)\%$ of the neutrino charged current interactions, indicating a steep increase of cross section with energy. The mean fractional hadronic energy of the $D^{*+}$ meson is $0.55 \pm 0.06$

Focused wave interactions with floating structures: A blind comparative study

The paper presents results from the Collaborative Computational Project in Wave Structure Interaction (CCP-WSI) Blind Test Series 2. Without prior access to the physical data, participants, with numerical methods ranging from low-fidelity linear models to fully non-linear Navier−Stokes (NS) solvers, simulate the interaction between focused wave events and two separate, taut-moored, floating structures: a hemispherical-bottomed cylinder and a cylinder with a moonpool. The ‘blind’ numerical predictions for heave, surge, pitch and mooring load, are compared against physical measurements. Dynamic time warping is used to quantify the predictive capability of participating methods. In general, NS solvers and hybrid methods give more accurate predictions; however, heave amplitude is predicted reasonably well by all methods; and a WEC-Sim implementation, with CFD-informed viscous terms, demonstrates comparable predictive capability to even the stronger NS solvers. Large variations in the solutions are observed (even among similar methods), highlighting a need for standardisation in the numerical modelling of WSI problems

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Neutral pion photoproduction from deuterium in the energy range 1/2 to 1 Bev

NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. Gamma rays from the decay of neutral pions photoproduced in the bremsstrahlung beam of the Caltech synchrotron from high density deuterium and hydrogen gas have been observed with a Thallium Chloride crystal gamma ray spectrometer. Integral gamma ray yields and gamma ray energy spectra have been obtained for several bremsstrahlung endpoint energies from 0.6 to 1.08 Bev at [theta] = 60° and 120° with respect to the bremsstrahlung beam. The resulting integral D/H ratios show no significant variation with bremsstrahlung energy in this range; the ratio for [theta] = 60° may be a percent or so lower than that for [theta] = 120° but the average over energy and angle is consistent with [...] YH = = 0.94 +/- 0.02 per nucleon. Gamma ray yields for 0.2 Bev ranges of incident photon energy have been calculated from the above integral yields using the photon difference method. The resulting differential D/H ratio may exhibit a broad minimum around 0.8 Bev. The results are consistent, however, with a constant value [...] = = 0.85 +/- 0.05 per nucleon, averaged over incident photon energy and spectrometer angle. It was possible to separate to some extent those observed gamma rays coming from the decay of [...] photoproduced singly from those from [...] multiply photoproduced, on the basis of their different energy spectra. Cross sections for single [...] photo-production from hydrogen obtained from the "singles" gamma rays are in general (but not complete) agreement with those obtained by more precise methods by Vette and Worlock. The D/H ratios for singly photoproducing [...] may exhibit a maximum for incident photon energy about 0.8 to 0.9 Bev for [theta] = 120°. n/p ratios calculated from the D/H ratios for singly photopro.ducing [...] are equal to the [...] ratios from deuterium obtained by Neugebauer et al., within the rather large errors on the n/p for incident photon energy >= 0.8 Bev for both [theta] = 60° and [theta] = 120°. The n/p ratio is significantly lower than the -/+ for [...], [theta] = 120°, possibly higher for [...], [theta] = 60°. Cross sections for multiply photoproducing [...] from hydrogen, obtained from the observed multiples gamma rays, are of the same order of magnitude (possibly somewhat larger) as those obtained for example by Bloch for charged pion pair production from hydrogen, and exhibit similar features: no large variation is apparent with incident photon energy, pion center of mass system angle or pion CMS kinetic energy. The D/H ratio for multiple [...] photoproduction is in general somewhat less than, but on the order of one, with possibly a minimum in the region around 0.8 to 0.9 Bev incident photon energy. The observed multiples gamma ray energy spectra are not measured with sufficient precision to distinguish between multiple pion kinetic energy spectra predicted on the bases of various proposed models for pion pair production. Some indication is found, however, that the observed pion kinetic energy spectrum (CMS) may be somewhat peaked toward higher energy for incident photon energies 0.7 and 0.8 Bev, toward lower energy for 0.9 and 0.99 Bev