First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study.

Purpose: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC).

Materials And Methods: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC.

Upper Aerodigestive Tract Endoscopy Combining Rigid Laryngoscopy and Flexible Endoscopy.

Upper Aerodigestive Tract Endoscopy (UATE) is recommended for initial examination of head and neck squamous cell carcinomas. Reducing delay of initial examination must be a challenge to manage head and neck cancers. We hereby describe the technic combining UATE and flexible endoscopy in a unique general anesthesia with overview of hypopharyngeal, larygeal, tracheal, esophageal, nasopharyngeal sub sites in a unique procedure with system of magnificense and to perform percutaneous gastrostomy during the same time before initiation of therapy.

Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial.

Importance: Nonclinical studies suggest that the combination of poly(ADP-ribose) polymerase and programmed cell death 1/programmed cell death-ligand 1 inhibitors has enhanced antitumor activity; however, the patient populations that may benefit from this combination have not been identified.

Objective: To evaluate whether the combination of avelumab and talazoparib is effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless of tumor type.

Design, Setting, And Participants: In this pan-cancer tumor-agnostic phase 2b nonrandomized controlled trial, patients with advanced BRCA1/2-altered or ATM-altered solid tumors were enrolled into 2 respective parallel cohorts.

Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial.

Importance: Preclinical data suggest that poly(ADP-ribose) polymerase (PARP) inhibitors have synergistic activity when combined with immune checkpoint inhibitors (ICIs); however, it is unknown which tumor types or molecular subtypes may benefit from this combination.

Objective: To investigate responses associated with the combination of avelumab and talazoparib in different tumor types and/or molecular subtypes.

Design, Setting, And Participants: In this phase 1b and 2 basket nonrandomized controlled trial, patients with advanced solid tumors were enrolled in the following cohorts: non-small cell lung cancer (NSCLC); DNA damage response (DDR)-positive NSCLC; triple-negative breast cancer (TNBC); hormone receptor-positive, human epidermal growth factor receptor 2 (ERBB2)-negative, DDR-positive breast cancer; recurrent, platinum-sensitive ovarian cancer (OC); recurrent, platinum-sensitive, BRCA1/2-altered OC; urothelial cancer; metastatic castration-resistant prostate cancer (mCRPC); DDR-positive mCRPC; and BRCA1/2- or ATM-altered solid tumors.

Novel Ionic Conducting Composite Membrane Based on Polymerizable Ionic Liquids.

In this work, the design and characterization of new supported ionic liquid membranes, as medium-temperature polymer electrolyte membranes for fuel-cell application, are described. These membranes were elaborated by the impregnation of porous polyimide Matrimid with different synthesized protic ionic liquids containing polymerizable vinyl, allyl, or methacrylate groups. The ionic liquid polymerization was optimized in terms of the nature of the used (photo)initiator, its quantity, and reaction duration.

Enhanced water and oxygen barrier performance of flexible polyurethane membranes for biomedical application.

In order to improve water and oxygen barrier properties, the surface of two commercial medical grade polyurethane (PU) membranes (Chronoflex® AR-LT and Bionate® II) was modified by a spray deposited film of poly(ethylene-co-vinyl alcohol) (EVOH). The influence of the temperature, the deposited layer thickness and the EVOH ethylene group percentage (27%, 32%, and 44% for EVOH27, EVOH32, and EVOH44, respectively) on the barrier properties of the PU/EVOH multilayered membranes was investigated. The increase of the EVOH layer thickness leads to higher oxygen barrier properties (the highest barrier improvement factor of 412 was obtained).

The Impact of Reactive Ionic Liquids Addition on the Physicochemical and Sorption Properties of Poly(Vinyl Alcohol)-Based Films.

A new type of hybrid polymeric-based film containing 1-(1,3-diethoxy-1,3-dioxopropan-2-ylo)-3-methylimidazolium bromide (RIL1_Br) and 1-(2-etoxy-2-oxoethyl)-3-methylimidazolium bromide (RIL2_Br) reactive ionic liquids was elaborated. Poly(vinyl alcohol) (PVA)-based films with 9-33 wt % of RILs were subsequently characterized using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), scanning electron microscopy (SEM), atomic force microscopy (AFM), thermogravimetric analysis (TGA) and TGA-FTIR. PVA-RIL films were also studied in tensile tests, contact angle and sorption measurements.

A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline Mutations (ABRAZO).

Purpose: To assess talazoparib activity in germline mutation carriers with advanced breast cancer.

Patients And Methods: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment.

Sulfonic Membrane Sorption and Permeation Properties: Complementary Approaches to Select a Membrane for Pervaporation.

In this contribution, the physical and chemical properties of the dense sulfonic membrane IonClad R4010 in the lithium form were studied to evaluate its potential application in pervaporation. To develop new membrane materials, it is necessary to know the influence of the membrane structure on the membrane equilibrium and transport properties. For this purpose, the sorption and permeation measurements of water and methanol in the liquid and vapor states were performed and correlated to the ion pairs/solvent interactions analyzed by the infrared spectroscopy.

Layered Poly(ethylene-co-vinyl acetate)/Poly(ethylene-co-vinyl alcohol) Membranes with Enhanced Water Separation Selectivity and Performance.

A three-layered membrane based on poly(ethylene-co-vinyl acetate) (EVA) and hydrolyzed EVA-poly(ethylene-co-vinyl alcohol) (EVOH), was elaborated by the surface hydrolysis of a dense EVA membrane. Because of the chemical modifications, the three-layered EVOH/EVA/EVOH membrane was characterized by the particular microstructure (amorphous EVA and semicrystalline EVOH) and the tunable hydrophilic/hydrophobic balance. Also, these modifications led to the membrane with the selective barrier properties compared with the pure EVA and completely hydrolyzed EVOH membranes.

Safety, virology and pharmacokinetics of oseltamivir in infants with laboratory-confirmed influenza: a Phase I/II, prospective, open-label, multicentre clinical trial.

Background: The influenza antiviral oseltamivir is not licensed for infants aged <1 year in most countries outside the United States. More information is needed on oseltamivir safety at different dosing levels in this vulnerable age group.

Methods: In this prospective, observational, non-randomized study, infants aged <1 year with laboratory-confirmed influenza were treated with oral oseltamivir for 5 days.

A part-randomized study of intravenous oseltamivir in adolescents and adults.

Seriously ill patients with influenza may be unable to take oral medication. The safety of intravenous oseltamivir was evaluated in adults and adolescents. This prospective, part-randomized study enrolled hospitalized patients aged ≥13 years with clinical or laboratory-confirmed influenza, who started study medication within 144 h of illness onset.

Safety, tolerability, and pharmacokinetics of intravenous oseltamivir: single- and multiple-dose phase I studies with healthy volunteers.

There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication.

A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase.

The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subtype B infected individuals undergoing routine drug resistance testing. We assayed virus samples for in vitro replicative capacity in the absence of drugs as well as in the presence of 15 individual drugs.

Principal component analysis of general patterns of HIV-1 replicative fitness in different drug environments.

To detect general patterns and temporal trends of HIV-1 resistance, we apply principal component analysis (PCA) to in vitro fitness data. Twenty-eight thousand virus samples, obtained between 2002 and 2008, were assayed for fitness in 16 to 21 selective environments. Fitness measurements are based on replication capacity (RC), which quantifies in vitro viral replication in a single cycle of infection.

Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity.

Background: The CPCRA 064 study examined the effect of structured treatment interruption (STI) of up to 4 months followed by salvage treatment in patients failing therapy with multi-drug resistant HIV. We examined the relationship between the reversion rate of major reverse transcriptase (RT) resistance-associated mutations and change in viral replication capacity (RC). The dataset included 90 patients with RC and genotypic data from virus samples collected at 0 (baseline), 2 and 4 months of STI.

Transport mechanisms of small molecules through polyamide 12/montmorillonite nanocomposites.

The aim of this work is to study the transport of small molecules through the hybrid systems polyamide 12 (PA12)/organo-modified montmorillonite (Cloisite 30B, C30B) prepared by melt blending, using two blending conditions. The transport mechanisms were investigated by using three probe molecules: nitrogen, water, and toluene. While a barrier effect appears clearly with nitrogen, this effect changes with the amount of fillers for water and disappears for toluene.

Comparison of standard PCR/cloning to single genome sequencing for analysis of HIV-1 populations.

To compare standard PCR/cloning and single genome sequencing (SGS) in their ability to reflect actual intra-patient polymorphism of HIV-1 populations, a total of 530 HIV-1 pro-pol sequences obtained by both sequencing techniques from a set of 17 ART naïve patient specimens was analyzed. For each specimen, 12 and 15 sequences, on average, were characterized by the two techniques. Using phylogenetic analysis, tests for panmixia and entropy, and Bland-Altman plots, no difference in population structure or genetic diversity was shown in 14 of the 17 subjects.

An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1.

Genetically diverse pathogens (such as Human Immunodeficiency virus type 1, HIV-1) are frequently stratified into phylogenetically or immunologically defined subtypes for classification purposes. Computational identification of such subtypes is helpful in surveillance, epidemiological analysis and detection of novel variants, e.g.

Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance.

Drug resistance is an important cause of antiretroviral therapy failure in human immunodeficiency virus (HIV)-infected patients. Mutations in the protease render the virus resistant to protease inhibitors (PIs). Gag cleavage sites also mutate, sometimes correlating with resistance mutations in the protease, but their contribution to resistance has not been systematically analyzed.

Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.

Objective: To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment.

Methods: Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA).

Permeation properties of poly(m-xylene adipamide) membranes.

The permeation properties of a semiaromatic polyamide, the poly(m-xylene adipamide) (MXD6), were investigated by water and carbon dioxide permeation experiments (pervaporation and gas permeation tests). Complementary microstructure informations were obtained from calorimetric measurements. Amorphous and semicrystalline MXD6 membranes were studied.

Quantitation of HER2 expression or HER2:HER2 dimers and differential survival in a cohort of metastatic breast cancer patients carefully selected for trastuzumab treatment primarily by FISH.

The selection of patients with HER2-positive breast cancer for treatment with trastuzumab is based on the measurement of HER2 protein expression by immunohistochemistry, or the presence of HER2 gene amplification by fluorescence in situ hybridization (FISH). By using multivariate analyses, we investigate the relationship between quantitative measurements of HER2 expression or HER2:HER2 dimers and objective response (Response Evaluation Criteria in Solid Tumors), time to progression, and breast cancer survival after trastuzumab treatment in a cohort of patients with metastatic breast cancer who were primarily selected for treatment by FISH. The VeraTag assay, a proximity-based assay designed to quantitate protein expression and dimerization in formalin-fixed, paraffin-embedded tissue specimens, was used to measure HER2 protein expression and HER2:HER2 dimer levels.

Polyepichlorhydrin membranes for alkaline fuel cells: sorption and conduction properties.

Polymer electrolytes, using a poly(epichlorhydrin-allyl glycidyl ether) copolymer as matrix, are shown to perform well in alkaline fuel cell electrolyte. An anion-conducting network is obtained by the incorporation of cyclic diamines, 1,4-diazabicyclo[2.2.