Hermannasmussen1961

The Society of Toxicologic Pathology (STP) explored current institutional practices for selecting between non-blinded versus blinded histopathologic evaluation during Good Laboratory Practice (GLP)-compliant, regulatory-type animal toxicity studies using a multi-question survey and STP-wide discussion (held at the 2019 STP annual meeting). Survey responses were received from 107 individuals representing 83 institutions that collectively employ 589 toxicologic pathologists. Most responses came from industry (N = 46, mainly biopharmaceutical or contract research organizations) and consultants (N = 24). For GLP-compliant animal toxicity studies, histopathologic evaluation usually involves initial (primary) non-blinded analysis, with post hoc informal blinded re-examination at the study pathologist's discretion to confirm subtle findings or establish thresholds. Initial blinded histopathologic evaluation sometimes is chosen by study pathologists to test formal hypotheses and/or by sponsors to address non-pathologist expectations about histopathology data objectivity. Current practice is that a blinded histopathologic evaluation is documented only if formal blinding (ie, using slides with coded labels) is employed, using simple statements without detailed methodology in the study protocol (or an amendment) and/or pathology report. Blinding is not an appropriate strategy for the initial histopathologic evaluation performed during pathology peer reviews of GLP-compliant animal toxicity studies. [Box see text].Mismatch between circulating influenza B viruses and vaccine strains occurs frequently. In a randomized, double-blind, controlled phase III clinical study, healthy children aged 6-35 months were randomized into three groups at a ratio of 211, received two doses of quadrivalent influenza vaccines (QIVs) or licensed trivalent influenza vaccines (TIVs). The primary objective was to evaluate the non-inferiority immunogenicity of QIV compared with the two TIVs, containing B/Victoria or B/Yamagata strain. Safety information was collected for 28 days after each vaccination. Serious adverse events (SAEs) were monitored for 6 months after the second vaccination. A total of 2146 subjects (QIV 1069, TIV-Vic 540, TIV-Yam 537) were enrolled in this study. QIV was found non-inferior to TIVs for shared strains (A/H1N1 and A/H3N2) and corresponding BY strain based on hemagglutination inhibition (HI) antibodies 28 days after the second dose of vaccination. The resulted geometric mean titer (GMT) ratios (QIV/TIV) were 0.98 (0.89, 1.07) for H1N1, 0.95 (0.85, 1.05) for H3N2 and 0.89 (0.81, 0.98) for BY. And the seroconversion rate differences (QIV-TIV) were -0.46% (-3.24%, 2.31%) for H1N1, -1.95% (-5.54%, 1.65%) for H3N2 and -3.58% (-8.11%, 0.95%) for BY. The BV strain in QIV did not reach the non-inferiority criteria, with GMT of 152.25 (vs. 161.02 of TIV-Vic) and seroconversion rate of 59.49% (vs. 66.85% of TIV-Vic). No increased safety concerns occurred in QIV group. Candidate QIV can provide good protection for children aged 6 to 35 months, and its immunogenicity and safety were proved.Clinical Trials Registration ClinicalTrials.gov number NCT03859141.PURPOSE Accurate preoperative staging of prostate cancer (PCa) is essential for treatment planning. Conventional imaging (CI) is limited in detection of metastases. Our primary aim was to determine if [18F]fluciclovine PET/CT is an early indicator of sub-clinical metastasis among patients with high-risk PCa. MATERIALS AND METHODS 68 patients with unfavorable intermediate to very high-risk PCa without systemic disease on CI were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection (EPLND). Diagnostic performance of [18F]fluciclovine PET/CT and CI for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined. RESULTS 57/68 patients completed the protocol, of which 31/57 had nodal metastasis on histology. [18F]fluciclovine PET/CT sensitivity and specificity in detecting nodal metastasis were 55.3% and 84.8% per-patient, 54.8% and 96.4% per-region (right and left pelvis, presacral and non-regional), respectively. Compared with CI, [18F]fluciclovine PET/CT had significantly higher sensitivity on patient-based (55.3% vs 33.3%; p less then 0.01) and region-based (54.8% vs 19.4%; p less then 0.01) analysis, detecting metastasis in 7 more patients and 22 more regions; with similar high specificity. Four additional patients had distant disease or other cancer detected on [18F]fluciclovine PET/CT which precluded surgery. Detection of metastasis was related to size of metastatic deposits within LNs, and overall metastatic burden. CONCLUSIONS [18F]fluciclovine PET/CT detects occult metastases not identified on CI and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.This phase Ⅱ, randomized, controlled trial aimed to evaluate the safety and immunogenicity of a various Sabin IPV preparations. Six hundred infants aged 60 ~ 90 days received one of five different vaccines low- (group A), medium- (group B) or high-D antigen content (group C) of an experimental Sabin IPV, control Sabin IPV (group D) or control Salk IPV (group E), on a 0-1-2 month schedule. Participants were observed and followed up within 30 days of each dose to assess safety. Serum samples were collected before the first dose and 30 days after the third dose to assess immunogenicity. After three doses, type-1 seroconversion rates of groups A-E were 99.1%, 100.0%, 99.1%, 99.0%, and 93.4%, respectively; type-2 seroconversion rates were 93.5%, 97.1%, 98.1%, 95.1%, and 91.5%, respectively; and type-3 seroconversion rates were 95.4%, 98.1%, 98.1%, 95.1%, and 100.0%, respectively. Only type-1 seroconversion rates differed significantly for group E. The incidences of injection-site redness (A 21.9%, B 23.7%, C 29.4%, D 16.2%, E 12.7%), swelling (A 6.7%, B 6.8%, C 5.0%, D 0.0%, E 1.7%) and pain (A 5.0%, B 6.8%, C 7.6%, D 0.0%, E 0.9%) all were significantly higher for experimental vaccines relative to control groups. No SAEs were detected related to vaccination, and most adverse reactions were mild or moderate in severity. Lonafarnib mouse In conclusion, the experimental Sabin IPVs with low-, medium-, and high-D antigen content all revealed good safety and immunogenicity profiles although being more reactogenic than the control vaccines.