Background This was a phase I/IIa study to investigate the tolerability, efficacy and pharmacokinetics (PK)/ pharmacodynamics (PD) of CRLX301, CDP-based nanoparticle formulation of docetaxel. Methods The study was conducted in two parts. In part 1, dose-escalation using a standard 3 + 3 design was performed in two dosing schedules (every week (QW) and every 3 weeks (Q3W)). Part 2 was comprised of a dose expansion at 75 mg/m2 Q3W. PK studies were performed on both dosing schedules. https://www.selleckchem.com/products/cx-5461.html Results Forty-two patients were recruited onto the study with a median age of 64(range 38-76); median number of prior systemic therapies was 5(range 0-10). Grade 3/4 treatment-related toxicities included neutropenia (21.4 %), infusion related reaction (11.9 %), anemia (7.1 %), fatigue (4.8 %), diarrhea (4.8 %), and peripheral neuropathy (4.8 %). The maximum tolerated dose was 75 mg/m2 given on the Q3W schedule and was not determined on the QW schedule. In this heavily pre-treated population, four patients (12.9 %) achieved stable disease (SD) ≥ 4 months and 2 patients (6.5 %) achieved partial response (PR) for a clinical benefit rate (CBR) of 19.4 % (6/31 patients). The PRs were seen in prostate and breast adenocarcinoma (one each). CRLX301 exhibited some PK advantages over docetaxel including higher retention of drug in plasma, slower clearance and controlled slow release of docetaxel from the carrier. Conclusions In this heavily pretreated patient population, the safety profile was acceptable for CRLX301 therapy. There was some evidence of preliminary tumor efficacy, but further work is necessary to find the optimal dose and schedule of this formulation.Clinicaltrials.gov trial registration number NCT02380677 (Date of registration March 2, 2015).Philosophers of medicine have formulated different accounts of the concept of disease. Which concept of disease one assumes has implications for what conditions count as diseases and, by extension, who may be regarded as having a disease (disease judgements) and for who may be accorded the social privileges and personal responsibilities associated with being sick (sickness judgements). In this article, we consider an ideal diagnostic test for coronavirus disease 2019 (COVID-19) infection with respect to four groups of people-positive and asymptomatic; positive and symptomatic; negative; and untested-and show how different concepts of disease impact on the disease and sickness judgements for these groups. The suggestion is that sickness judgements and social measures akin to those experienced during the current COVID-19 outbreak presuppose a concept of disease containing social (risk of) harm as a component. We indicate the problems that arise when adopting this kind of disease concept beyond a state of emergency.Fungal pathogens are important determinants of plant dynamics in the environment. These pathogens can cause plant death and occasionally yield losses in crops, even at low initial densities in the soil. The objective of this study was to select and evaluate fungal antagonistic bacteria and to determine their biological control capacity in soybean seedlings. A total of 877 strains from the genera Pseudomonas, Bacillus, and Paraburkholderia/Burkholderia were screened, and their antagonistic effects on fungi frequently found in seeds were evaluated using four methods quadruple plating, paired culture confrontation, strain containment, and inoculation of soybean seeds. The experimental design was completely randomized, with three replications for the first three methods and five replications in a 3 × 9 factorial scheme for the fourth treatment. The strains with the highest biotechnological potential were inoculated into soybean seeds to evaluate the biological control of fungi that attack this crop at germination. Seventy-nine strains presented some type of antagonistic effect on the tested fungi, with two strains presenting a broader antagonistic action spectrum in the seed test. In addition to the antagonistic potential, strains BR 10788 and BR 11793, when simultaneously inoculated or alone, significantly increased the seedling dry matter mass, and promoted the growth of soybean seedlings even in the presence of most fungi. Thus, this study demonstrated the efficiency of the antagonistic activity of these strains in relation to the target fungi, which proved to be potential agents for biological control.We evaluated a novel transcription-reverse transcription concerted reaction (TRC) assay that can detect influenza A and B within 15 min using nasopharyngeal swab and gargle samples obtained from patients with influenza-like illness, between January and March 2018 and between January and March 2019. Based on the combined RT-PCR and sequencing results, in the nasal swabs, the sensitivity and specificity of TRC for detecting influenza were calculated as 1.000 and 1.000, respectively. In the gargle samples, the sensitivity and specificity of TRC were 0.946 and 1.000, respectively. The TRC assay showed comparable performance to RT-PCR in the detection of influenza viruses. Gastroesophageal reflux disease (GERD) is a commonly diagnosed gastrointestinal disorder, with a substantial impact on the quality of life. The underlying pathophysiology of GERD is multifactorial and incompletely understood. Abnormal gastric electrical activity, measured using electrogastrography (EGG), may contribute. This study aimed to systematically review and meta-analyse the existing literature in which EGG was used in patients with GERD. Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normogastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality. In total, 591 participants (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD - 1.18, 95%CI - 1.84, - 0.52) and 18.7% (SMD - 1.11, 95%CI - 1.55, - 0.68) less of the preprandial and postprandial recording time in normogastric frequency ranges, respectively, compared to healthy controls.