Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30-50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3-4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90-100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.Immune checkpoint blockade has become standard care for patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC). Here the authors present the results of a non-randomized phase Ib/IIa trial, reporting safety and efficacy of neoadjuvant nivolumab monotherapy and nivolumab plus ipilimumab prior to standard-of-care surgery in patients with HNSCC. .Otorhinolaryngolog

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

Condensed rotational separation of CO2 from natural gas

This article describes measurements of methane purification by condensed rotational separation. First, the separation concept is introduced. Then the test-setup and measurements are described. The thermodynamic performance of the system is compared with thermodynamic predictions and is found to be in good agreement. The separation performance of the centrifugal separator is addressed. © 2009 American Institute of Chemical Engineers AIChE J, 201

Creeping film model for condensed centrifugal separation processes

In a new process of separating high concentrations of gaseous contaminants like water vapor, CO2 and H2S from well gas streams, the contaminants are condensed and subsequently removed in a centrifugal separator. This paper presents an analytical model for the formation of a thin liquid film inside the small channels of a vertically oriented rotating phase separator. Film behavior is investigated under the combined influence of centrifugal and gravitational forces. At high gas throughput the shear forces at the interface between the gas flow and the liquid film, and the resulting pressure drop over the channel, are considered as well. The gas velocity through the channels is corrected for the displacement effect of the liquid film. Solutions are presented for several channel heights at various operating conditions, and for gas flow in upward and downward direction

Performance of a novel rotating gas-liquid separator

A novel gas separation process makes use of a rotating phase separator to separate micron-sized droplets from a gas stream. Based on an industrial scale design, a water/air separator is constructed and tested. The first experiment concerns the drainage of large fractions of separated liquid. During operation, drainage is observed via windows and a descriptive model is formulated. Because of the major influence on overall separation efficiency, liquid drainage is a key issue in the separator design. The second experiment comprises a droplet collection efficiency measurement using micron-sized droplets dispersed within the airstream. The separation efficiency of fine droplet removal is measured. This is an important factor in reducing capital costs