121 research outputs found
Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial
Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.
Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients.
Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60.
Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients
A highly mutagenised barley (cv. Golden Promise) TILLING population coupled with strategies for screening-by-sequencing
Background:We developed and characterised a highly mutagenised TILLING population of the barley (Hordeum vulgare) cultivar Golden Promise. Golden Promise is the 'reference' genotype for barley transformation and a primary objective of using this cultivar was to be able to genetically complement observed mutations directly in order to prove gene function. Importantly, a reference genome assembly of Golden Promise has also recently been developed. As our primary interest was to identify mutations in genes involved in meiosis and recombination, to characterise the population we focused on a set of 46 genes from the literature that are possible meiosis gene candidates. Results:Sequencing 20 plants from the population using whole exome capture revealed that the mutation density in this population is high (one mutation every 154 kb), and consequently even in this small number of plants we identified several interesting mutations. We also recorded some issues with seed availability and germination. We subsequently designed and applied a simple two-dimensional pooling strategy to identify mutations in varying numbers of specific target genes by Illumina short read pooled-amplicon sequencing and subsequent deconvolution. In parallel we assembled a collection of semi-sterile mutants from the population and used a custom exome capture array targeting the 46 candidate meiotic genes to identify potentially causal mutations. Conclusions:We developed a highly mutagenised barley TILLING population in the transformation competent cultivar Golden Promise. We used novel and cost-efficient screening approaches to successfully identify a broad range of potentially deleterious variants that were subsequently validated by Sanger sequencing. These resources combined with a high-quality genome reference sequence opens new possibilities for efficient functional gene validation.Miriam Schreiber, Abdellah Barakate, Nicola Uzrek, Malcolm Macaulay, Adeline Sourdille, Jenny Morris, Pete E. Hedley, Luke Ramsay and Robbie Waug
Effects of the Intragastric Balloon MedSil® on Weight Loss, Fat Tissue, Lipid Metabolism, and Hormones Involved in Energy Balance
Short-term effects of intragastric balloon in association with conservative therapy on weight loss: a meta-analysis
The effect of naloxone on trigemino-hypoglossal reflex inhibited by periaqueductal central gray stimulation in rats
‘Death and his body-servant’: health, architecture and missionary endeavour at the Anelcauhat Mission House, Vanuatu
Remaining healthy was a major consideration for both indigenous and European peoples in the New Hebrides (now Vanuatu) during early contact. While local communities were often devastated by introduced disease, new missionaries sought practical ways to overcome the impact of tropical ailments that they considered to undermine the effectiveness of their activities. From the early 1850s onwards, Presbyterian missionaries in the southern New Hebrides began to construct ‘healthy’ homes, of which the surviving masonry mission house at Anelcauhat, Aneityum (1852-3) forms the earliest standing example. This paper draws on the results of both above- and in-ground archaeological recording to examine how the surviving structure reflects nineteenth-century ideas about illness and well-being before discussing the wider trajectory of such house construction, and associated matters connected with local communities, health and architecture that potentially impacted on missionary endeavour
New perspectives for hydrocarbon prospecting in the Sokołów–Pogwizdów region (Carpathian Foredeep) as show by reprocessing of 3D seismic data
Reprocessing of 3D seismic data from the Carpathian Foreland and new interpretation techniques enabled more accurate mapping of structure and facies distribution of Miocene series and their bedrock. The reprocessing of a part of Sokołów Małopolski–Smolarzyny, 2001 3D seismic survey carried out in 2006 was focused on the Pogwizdów structure. Application of GeoProbeŽ software and the detailed analysis of seismic trace attributes along with the structural interpretation gave new information on morphology of the pre-Miocene bedrock and Miocene series. The area of erosional channels (paleovalleys), where anhydrite sediments and probably the Baranów Beds were distinguished, is particularly interesting as it is characterized by some distinctive anomalies of the analyzed seismic attributes. The evidence for presence of anhydrite within the so-called anhydrite-less island significantly enhances probability of discovering new gas fields with the Baranów Beds as reservoirs and anhydrites as a seal. The number of potential gas fields should compensate for their small reserves
Evaluation of nutritional information as an element influencing consumer behavior in gastronomy services
The aim of this study was the evaluation of nutritional information provided by frontline staff as an element influencing consumer behavior in gastronomy services. The empirical research was conducted under the project “The consumer in the market of catering services”, number 507-30-102-M00094-99, realized in the Chair of Gastronomy and Hospitality Management in the Faculty of Human Nutrition and Consumer Sciences at the Warsaw University of Life Sciences – SGGW. Quantitative research on the sample of 403 persons using purposive sampling were conducted in June 2016. The criteria of age (18–35), living in large cities as well as the fact of eating out. </jats:p
Prospects for the development of the sector of agricultural biogas plant in Poland
Produkcja i energetyczne wykorzystanie biogazu rolniczego jest jedną z metod pozyskiwania energii odnawialnej, która dopiero zaczyna rozwijać się w Polsce. Technologia ta jest natomiast rozpowszechniona i od wielu lat stosowana w krajach takich jak: Dania, Austria czy Niemcy. Polska posiada duży potencjał energetyczny krajowego rolnictwa. Zakłada on m.in. wykorzystanie produktów ubocznych rolnictwa oraz przemysłu rolno-spożywczego. Energetyczne wykorzystanie biogazu jest dla Polski szansą na spełnienie unijnych zobowiązań dotyczących produkcji energii z OZE. Obecnie inwestowanie w biogazownie rolnicze, wciąż wiąże się z dużą niepewnością, która wynika m.in. z braku transparentnego systemu wsparcia finansowego oraz licznych wahań w zakresie obowiązujących aktów prawnych.Energy production and use of agricultural biogas is one of methods of acquiring renewable energy, which is just beginning to develop in Poland. This technology is widespread and used for many years in countries such as Denmark, Austria or Germany. Poland has a large energy potential of the national agriculture. It assumes in using by-products of agriculture and agri-food industry. Energy use of biogas is a chance for Poland to fulfilment the EU's commitments on energy production from RES. Currently, investing in biogas plants, is still associated with large uncertainties that for ex. in the absence of a transparent system of financial support and numerous variations in terms of existing legislation
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