71 research outputs found

    Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206

    Get PDF
    Background Despite remarkable results with salvage standard-dose or high-dose chemotherapy ∼15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and methods Single arm phase II trial investigating pembrolizumab 200 mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no curable options. Patients age ≥18 with GCT who progressed after first-line cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or standard-dose chemotherapy) were eligible. Centrally assessed programmed death-ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end point was overall response rate using immune-related response criteria. Simon two-stage design with type I error 20% and power 80% was utilized. Results Twelve male patients were enrolled. Median age was 38 years. All patients had nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615 (range 1–32, 760) and hCG 4 (range 0.6–37, 096). Six patients had late relapse (>2 years). Median number of previous chemotherapy regimens was 3. Six patients received prior high-dose chemotherapy. Two patients had positive PD-L1 staining (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1–8). There were six grade 3 adverse events. No immune-related adverse events were reported. No partial or complete responses were observed. Two patients achieved radiographic stable disease for 28 and 19 weeks, respectively; both had continued rising AFP level despite radiographic stability and had negative PD-L1 staining. Conclusion This is the first reported trial evaluating immune checkpoint inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have clinically meaningful single-agent activity in refractory GCT

    Deagrarianisation and forest revegetation in a biodiversity hotspot on the Wild Coast, South Africa

    Get PDF
    Deagraianisation is a worldwide phenomenon with widespread social, ecological and economic effects yet with little consensus on the local or higher level causes. There have been contested views on the causes and consequences of deagrarianisation on South Africa’s Wild Coast, which is an international biodiversity hotspot. Using GIS, household interviews and ecological sampling, we compared the perspectives of current and former cultivators as to why some have abandoned farming, whilst also tracking the uses and woody plant cover and composition of fields abandoned at different periods. The GIS analysis showed that field abandonment had been ongoing over several decades, with a decline from 12.5 % field cover in 1961 to 2.7 % in 2009. The area of forests and woodlands almost doubled in the corresponding period. There was a distinct peak in field abandonment during the time of political transition at the national level in the early 1990s. This political change led to a decrease in government support for livestock farming, which in turn resulted in reduced animal draught power at the household and community level, and hence reduced cropping. The study showed it is largely the wealthier households that have remained in arable agriculture and that the poorer households have abandoned farming. The abandoned fields show a distinct trend of increasing woody biomass and species richness with length of time since abandonment, with approximately three woody plant species added per decade. Most local respondents dislike the increases in forest and woodland extent and density because of anxiety about wild animals causing harm to crops and even humans, and the loss of an agricultural identity to livelihoods and the landscape

    Photonic and magnetic dual responsive molecularly imprinted polymers preparation, recognition characteristics and.pdf

    No full text
    Parabens are alkyl esters of p-hydroxybenzoic acid and are used as antimicrobial preservatives in a range of consumer products, including cosmetics, pharmaceuticals, and foodstuffs. Despite their widespread use, prior to this study, paraben concentrations in foodstuffs from China and human dietary exposure to these chemicals have been unknown. In this study, concentrations of six parabens were determined in 13 categories of food samples (n = 282), including cereals and cereal products, meat, fish and seafood, eggs, dairy products, bean products, fruits, vegetables, cookies, beverages, cooking oils, condiments, and others, collected from nine cities in China. Almost all (detection rate: 99%) food samples contained at least one of the parabens analyzed, and the total concentrations (Sigma Parabens; sum of six parabens) ranged from below limit of quantification (LOQ) to 2530 ng/g fresh weight, with an overall mean value of 39.3 ng/g. Methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP) were the major paraben analogs found in foodstuffs, and these compounds accounted for 59%, 24%, and 10%, respectively, of Sigma Paraben concentrations. Although the mean concentrations of Sigma Parabens varied among different categories of food items (from 0.839 ng/g in beverages to 100 ng/g in vegetables), the concentrations were not statistically significant among the 13 food categories, including canned foodstuffs. Estimated daily intake (EDI) of parabens was based on the measured concentrations in foods and the corresponding daily food ingestion rates. The mean and 95th percentile values for EDI were 1010 and 3040 ng/kg body weight (bw)/day for adult men and 1060 and 3170 ng/kg bw/day for adult women, respectively. (C) 2013 Elsevier Ltd. All rights reserved.Parabens are alkyl esters of p-hydroxybenzoic acid and are used as antimicrobial preservatives in a range of consumer products, including cosmetics, pharmaceuticals, and foodstuffs. Despite their widespread use, prior to this study, paraben concentrations in foodstuffs from China and human dietary exposure to these chemicals have been unknown. In this study, concentrations of six parabens were determined in 13 categories of food samples (n = 282), including cereals and cereal products, meat, fish and seafood, eggs, dairy products, bean products, fruits, vegetables, cookies, beverages, cooking oils, condiments, and others, collected from nine cities in China. Almost all (detection rate: 99%) food samples contained at least one of the parabens analyzed, and the total concentrations (Sigma Parabens; sum of six parabens) ranged from below limit of quantification (LOQ) to 2530 ng/g fresh weight, with an overall mean value of 39.3 ng/g. Methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP) were the major paraben analogs found in foodstuffs, and these compounds accounted for 59%, 24%, and 10%, respectively, of Sigma Paraben concentrations. Although the mean concentrations of Sigma Parabens varied among different categories of food items (from 0.839 ng/g in beverages to 100 ng/g in vegetables), the concentrations were not statistically significant among the 13 food categories, including canned foodstuffs. Estimated daily intake (EDI) of parabens was based on the measured concentrations in foods and the corresponding daily food ingestion rates. The mean and 95th percentile values for EDI were 1010 and 3040 ng/kg body weight (bw)/day for adult men and 1060 and 3170 ng/kg bw/day for adult women, respectively. (C) 2013 Elsevier Ltd. All rights reserved
    • …
    corecore