617 research outputs found
Is Embedding Entailed in Consumer Valuation of Food Safety Characteristics?
Consumers’ preferences for food safety characteristics are investigated with particular focus on existence of an embedding effect. Embedding exists if consumer valuation of food safety is insensitive to scope. Two choice experiments have been conducted valuing food safety in respectively minced pork and chicken breasts, exemplified by avoiding human risks of Salmonella infections and strengthening the restrictions of using antibiotics in the pork production and in terms of avoiding human risks of Salmonella and Campylobacter infections respectively. The results showed no indications of an embedding effect between the food safety characteristics, in neither of the cases.Valuation, Choice Experiment, Market Goods, Food Safety, Embedding., Agricultural and Food Policy, Food Consumption/Nutrition/Food Safety,
CA19-9 as a Potential Target for Radiolabeled Antibody-Based Positron Emission Tomography of Pancreas Cancer.
Introduction. Sensitive and specific imaging of pancreas cancer are necessary for accurate diagnosis, staging, and treatment. The vast majority of pancreas cancers express the carbohydrate tumor antigen CA19-9. The goal of this study was to determine the potential to target CA19-9 with a radiolabeled anti-CA19-9 antibody for imaging pancreas cancer. Methods. CA19-9 was quantified using flow cytometry on human pancreas cancer cell lines. An intact murine anti-CA19-9 monoclonal antibody was labeled with a positron emitting radionuclide (Iodine-124) and injected into mice harboring antigen positive and negative xenografts. MicroPET/CT were performed at successive time intervals (72 hours, 96 hours, 120 hours) after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the images. Results. Antigen expression by flow cytometry revealed approximately 1.3 × 10(6) CA19-9 antigens for the positive cell line and no expression in the negative cell line. Pancreas xenograft imaging with Iodine-124-labeled anti-CA19-9 mAb demonstrated an average tumor to blood ratio of 5 and positive to negative tumor ratio of 20. Conclusion. We show in vivo targeting of our antigen positive xenograft with a radiolabeled anti-CA19-9 antibody. These data demonstrate the potential to achieve anti-CA19-9 antibody based positron emission tomography of pancreas cancer
Segregation of chromosome arms in growing and non-growing <i>Escherichia coli </i>cells
In slow-growing Escherichia coli cells the chromosome is organized with its left (L) and right (R) arms lying separated in opposite halves of the nucleoid and with the origin (O) in-between, giving the pattern L-O-R. During replication one of the arms has to pass the other to obtain the same organization in the daughter cells: L-O-R L-O-R. To determine the movement of arms during segregation six strains were constructed carrying three coloured loci: the left and right arms were labeled with red and cyan fluorescent-proteins, respectively, on loci symmetrically positioned at different distances from the central origin, which was labeled with green-fluorescent protein. In non-replicating cells with the predominant spot pattern L-O-R, initiation of replication first resulted in a L-O-O-R pattern, soon changing to O-L-R-O. After replication of the arms the predominant spot patterns were, L-O-R L-O-R, O-R-L R-O-L or O-L-R L-O-R indicating that one or both arms passed an origin and the other arm. To study the driving force for these movements cell growth was inhibited with rifampicin allowing run-off DNA synthesis. Similar spot patterns were obtained in growing and non-growing cells, indicating that the movement of arms is not a growth-sustained process, but may result from DNA synthesis itself. The distances between loci on different arms (LR-distances) and between duplicated loci (LL- or RR-distances) as a function of their distance from the origin, indicate that in slow-growing cells DNA is organized according to the so-called sausage model and not accordingto the doughnut model
Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus
Source at https://doi.org/10.1186/s12933-016-0492-4.Background: Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. Adipokine imbalance in the presence of metabolic dysfunction may be a key event in promoting CVD. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy.
Methods: This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy X-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting adiponectin and leptin levels were measured four times during pregnancy and at follow-up.
Results: We found the L/A ratio higher in GDM women during both pregnancy and follow-up compared to nonGDM women. A high L/A ratio during pregnancy was associated with CV risk based on lipid ratios at follow-up, especially the TG/HDL-C ratio. Further, interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy. Finally, low adiponectin levels independently predicted increased lipid ratios at follow-up.
Conclusions: Taken together, our findings suggest that high L/A ratio in pregnancy and in particularly in those with GDM are associated with an unfavorable CVD risk profile during follow-up. Future studies should investigate if a dysregulated leptin and adiponectin profile during pregnancy is associated with atherosclerotic disease during long-term follow-up
Targeting CEA in Pancreas Cancer Xenografts with a Mutated scFv-Fc Antibody Fragment
BackgroundSensitive antibody-based tumor targeting has the potential not only to image metastatic and micrometastatic disease, but also to be the basis of targeted therapy. The vast majority of pancreas cancers express carcinoembryonic antigen (CEA). Thus, we sought to evaluate the potential of CEA as a pancreatic cancer target utilizing a rapidly clearing engineered anti-CEA scFv-Fc antibody fragment with a mutation in the Fc region [anti-CEA scFv-Fc H310A].MethodsImmunohistochemistry (IHC) with the antibody fragment was used to confirm expression of CEA on human pancreas cancer specimens. In vivo tumor targeting was evaluated by tail vein injection of I124-labeled anti-CEA scFv-Fc(H310A) into mice harboring CEA-positive and -negative xenografts. MicroPET/CT imaging was performed at successive time intervals. Radioactivity in blood and tumor was measured after the last time point. Additionally, unlabeled anti-CEA scFv-Fc(H310A) was injected into CEA-positive tumor bearing mice and ex vivo IHC was performed to identify the presence of the antibody to define the microscopic intratumoral pattern of targeting.ResultsModerate to strong staining by IHC was noted on 84% of our human pancreatic cancer specimens and was comparable to staining of our xenografts. Pancreas xenograft imaging with the radiolabeled anti-CEA scFv-Fc(H310A) antibody demonstrated average tumor/blood ratios of 4.0. Immunolocalization demonstrated peripheral antibody fragment penetration of one to five cell diameters (0.75 to 1.5 μm).ConclusionsWe characterized a preclinical xenograft model with respect to CEA expression that was comparable to human cases. We demonstrated that the anti-CEA scFv-Fc(H310A) antibody exhibited antigen-specific tumor targeting and shows promise as an imaging and potentially therapeutic agent
Clostridium difficile:real-time PCR detection of toxin genes in faecal samples is more sensitive compared to toxigenic culture
Identification of copy number variants from exome sequence data
Background
With advances in next generation sequencing technologies and genomic capture techniques, exome sequencing has become a cost-effective approach for mutation detection in genetic diseases. However, computational prediction of copy number variants (CNVs) from exome sequence data is a challenging task. Whilst numerous programs are available, they have different sensitivities, and have low sensitivity to detect smaller CNVs (1–4 exons). Additionally, exonic CNV discovery using standard aCGH has limitations due to the low probe density over exonic regions. The goal of our study was to develop a protocol to detect exonic CNVs (including shorter CNVs that cover 1–4 exons), combining computational prediction algorithms and a high-resolution custom CGH array.
Results
We used six published CNV prediction programs (ExomeCNV, CONTRA, ExomeCopy, ExomeDepth, CoNIFER, XHMM) and an in-house modification to ExomeCopy and ExomeDepth (ExCopyDepth) for computational CNV prediction on 30 exomes from the 1000 genomes project and 9 exomes from primary immunodeficiency patients. CNV predictions were tested using a custom CGH array designed to capture all exons (exaCGH). After this validation, we next evaluated the computational prediction of shorter CNVs. ExomeCopy and the in-house modified algorithm, ExCopyDepth, showed the highest capability in detecting shorter CNVs. Finally, the performance of each computational program was assessed by calculating the sensitivity and false positive rate.
Conclusions
In this paper, we assessed the ability of 6 computational programs to predict CNVs, focussing on short (1–4 exon) CNVs. We also tested these predictions using a custom array targeting exons. Based on these results, we propose a protocol to identify and confirm shorter exonic CNVs combining computational prediction algorithms and custom aCGH experiments
Breeding for diversity – political implications and new pathways for the future
At present, around 95% of organic production is based on crop varieties that were bred for the conventional high-input sector, lacking important traits required under organic and low-input production conditions. Populations with a high level of genetic diversity are promising for OA (organic agriculture) conditions due to their adaptation, resilience and performance stability in different environments. Organic farming will benefit from cultivars (populations, varieties) that can cope with multiple stresses such as weeds, diseases, pests, climate change and low nitrogen input from manure. In the COBRA project (Coordinating Organic Plant Breeding Activities for diversity), plant genetic diversity and its potential have been investigated from both an agronomic and a legal point of view. This booklet aims to give insight into the socioeconomic and legal aspects of organic plant breeding including High Diversity breeding. COBRA is a three year (2013-16) European project under the Core Organic II program. It has linked up existing organic breeding activities by a multi-partner coordinated approach. The pillars of the COBRA project are:
• Seed health
• Response of crops to multiple stresses
• Breeding efficiency for organic systems
• Networking and coordination
• Socioeconomic and legal issues related to organic plant breeding
Through case studies, several COBRA partners investigated how different quality requirements can be imbedded in local breeding initiatives and promote organic seed use and production. They also studied how different barriers affect organic seed production and breeding. Case studies from UK, Denmark, Slovenia, Italy and the outputs of the COBRA workshop “Financing of organic plant breeding” (Freising, Germany, 2015) are presented in the booklet
Comparison of the Population Excess Fraction of <i>Chlamydia trachomatis</i> Infection on Pelvic Inflammatory Disease at 12-months in the Presence and Absence of Chlamydia Testing and Treatment:Systematic Review and Retrospective Cohort Analysis
Background: The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. Methods: We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. Results: The systematic review identified a single study, a randomised control led trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15-10.75); Denmark: 3.84%(3.26-4.45); screened-arm POPI-RCT: 0.99%(0.00-29.06)). In the absence of active chlamydia treatment 26.44% (11.57-46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13- 184 cases of PID per 100,000 tested women in the presence of testing and treatment. Conclusion: Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women
Defining the optimal biological monotherapy in rheumatoid arthritis: a systematic review and meta-analysis of randomised trials
Objectives
To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.
Methods
We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.
Results
The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included “DMARD-naïve”, and 20 “DMARD-Inadequate responder” (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).
Conclusions
Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice
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