Cost Analysis of Various Low Pathogenic Avian Influenza Surveillance Systems in the Dutch Egg Layer Sector

Background: As low pathogenic avian influenza viruses can mutate into high pathogenic viruses the Dutch poultry sector implemented a surveillance system for low pathogenic avian influenza (LPAI) based on blood samples. It has been suggested that egg yolk samples could be sampled instead of blood samples to survey egg layer farms. To support future decision making about AI surveillance economic criteria are important. Therefore a cost analysis is performed on systems that use either blood or eggs as sampled material. Methodology/Principal Findings: The effectiveness of surveillance using egg or blood samples was evaluated using scenario tree models. Then an economic model was developed that calculates the total costs for eight surveillance systems that have equal effectiveness. The model considers costs for sampling, sample preparation, sample transport, testing, communication of test results and for the confirmation test on false positive results. The surveillance systems varied in sampled material (eggs or blood), sampling location (farm or packing station) and location of sample preparation (laboratory or packing station). It is shown that a hypothetical system in which eggs are sampled at the packing station and samples prepared in a laboratory had the lowest total costs (i.e. J 273,393) a year. Compared to this a hypothetical system in which eggs are sampled at the farm and samples prepared at a laboratory, and the currently implemented system in which blood is sampled at the farm and samples prepared at a laboratory have 6 % and 39 % higher costs respectively

Evaluating Surveillance Strategies for the Early Detection of Low Pathogenicity Avian Influenza Infections

In recent years, the early detection of low pathogenicity avian influenza (LPAI) viruses in poultry has become increasingly important, given their potential to mutate into highly pathogenic viruses. However, evaluations of LPAI surveillance have mainly focused on prevalence and not on the ability to act as an early warning system. We used a simulation model based on data from Italian LPAI epidemics in turkeys to evaluate different surveillance strategies in terms of their performance as early warning systems. The strategies differed in terms of sample size, sampling frequency, diagnostic tests, and whether or not active surveillance (i.e., routine laboratory testing of farms) was performed, and were also tested under different epidemiological scenarios. We compared surveillance strategies by simulating within-farm outbreaks. The output measures were the proportion of infected farms that are detected and the farm reproduction number (Rh). The first one provides an indication of the sensitivity of the surveillance system to detect within-farm infections, whereas Rh reflects the effectiveness of outbreak detection (i.e., if detection occurs soon enough to bring an epidemic under control). Increasing the sampling frequency was the most effective means of improving the timeliness of detection (i.e., it occurs earlier), whereas increasing the sample size increased the likelihood of detection. Surveillance was only effective in preventing an epidemic if actions were taken within two days of sampling. The strategies were not affected by the quality of the diagnostic test, although performing both serological and virological assays increased the sensitivity of active surveillance. Early detection of LPAI outbreaks in turkeys can be achieved by increasing the sampling frequency for active surveillance, though very frequent sampling may not be sustainable in the long term. We suggest that, when no LPAI virus is circulating yet and there is a low risk of virus introduction, a less frequent sampling approach might be admitted, provided that the surveillance is intensified as soon as the first outbreak is detected

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Variability in childhood allergy and asthma across ethnicity, language, and residency duration in El Paso, Texas: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>We evaluated the impact of migration to the USA-Mexico border city of El Paso, Texas (USA), parental language preference, and Hispanic ethnicity on childhood asthma to differentiate between its social and environmental determinants.</p> <p>Methods</p> <p>Allergy and asthma prevalence was surveyed among 9797 fourth and fifth grade children enrolled in the El Paso Independent School District. Parents completed a respiratory health questionnaire, in either English or Spanish, and a sub-sample of children received spirometry testing at their school. Here we report asthma and allergy outcomes across ethnicity and El Paso residency duration.</p> <p>Results</p> <p>Asthma and allergy prevalence increased with longer duration of El Paso residency independent of ethnicity and preferred language. Compared with immigrants who arrived in El Paso after entering first grade (18%), lifelong El Paso residents (68%) had more prevalent allergy (OR, 1.72; 95% CI, 1.32 - 2.24), prevalent asthma (OR, 1.75; 95% CI, 1.24 - 2.46), and current asthma (OR, 2.01; 95% CI, 1.37 - 2.95). Spirometric measurements (FEV₁/FVC and FEF_25-75) also declined with increasing duration of El Paso residency (0.16% and 0.35% annual reduction, respectively).</p> <p>Conclusion</p> <p>These findings suggest that a community-wide environmental exposure in El Paso, delayed pulmonary development, or increased health of immigrants may be associated with allergy and asthma development in children raised there.</p

PeanutMap: an online genome database for comparative molecular maps of peanut

BACKGROUND: Molecular maps have been developed for many species, and are of particular importance for varietal development and comparative genomics. However, despite the existence of multiple sets of linkage maps, databases of these data are lacking for many species, including peanut. DESCRIPTION: PeanutMap provides a web-based interface for viewing specific linkage groups of a map set. PeanutMap can display and compare multiple maps of a set based upon marker or trait correspondences, which is particularly important as cultivated peanut is a disomic tetraploid. The database can also compare linkage groups among multiple map sets, allowing identification of corresponding linkage groups from results of different research projects. Data from the two published peanut genome map sets, and also from three maps sets of phenotypic traits are present in the database. Data from PeanutMap have been incorporated into the Legume Information System website to allow peanut map data to be used for cross-species comparisons. CONCLUSION: The utility of the database is expected to increase as several SSR-based maps are being developed currently, and expanded efforts for comparative mapping of legumes are underway. Optimal use of these data will benefit from the development of tools to facilitate comparative analysis

Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death

The purinergic signalling system, which uses purines and pyrimidines as chemical transmitters, and purinoceptors as effectors, is deeply rooted in evolution and development and is a pivotal factor in cell communication. The ATP and its derivatives function as a 'danger signal' in the most primitive forms of life. Purinoceptors are extraordinarily widely distributed in all cell types and tissues and they are involved in the regulation of an even more extraordinary number of biological processes. In addition to fast purinergic signalling in neurotransmission, neuromodulation and secretion, there is long-term (trophic) purinergic signalling involving cell proliferation, differentiation, motility and death in the development and regeneration of most systems of the body. In this article, we focus on the latter in the immune/defence system, in stratified epithelia in visceral organs and skin, embryological development, bone formation and resorption, as well as in cancer. Cell Death and Disease (2010) 1, e9; doi:10.1038/cddis.2009.11; published online 14 January 201

Receptor-Associated Protein (RAP) Plays a Central Role in Modulating Aβ Deposition in APP/PS1 Transgenic Mice

BACKGROUND: Receptor associated protein (RAP) functions in the endoplasmic reticulum (ER) to assist in the maturation of several membrane receptor proteins, including low density lipoprotein receptor-related protein (LRP) and lipoprotein receptor 11 (SorLA/LR11). Previous studies in cell and mouse model systems have demonstrated that these proteins play roles in the metabolism of the amyloid precursor protein (APP), including processes involved in the generation, catabolism and deposition of beta-amyloid (Abeta) peptides. METHODOLOGY/PRINCIPAL FINDINGS: Mice transgenic for mutant APPswe and mutant presenilin 1 (PS1dE9) were mated to mice with homozygous deletion of RAP. Unexpectedly, mice that were homozygous null for RAP and transgenic for APPswe/PS1dE9 showed high post-natal mortality, necessitating a shift in focus to examine the levels of amyloid deposition in APPswe/PS1dE9 that were hemizygous null for RAP. Immunoblot analysis confirmed 50% reductions in the levels of RAP with modest reductions in the levels of proteins dependent upon RAP for maturation [LRP trend towards a 20% reduction ; SorLA/LR11 statistically significant 15% reduction (p<0.05)]. Changes in the levels of these proteins in the brains of [APPswe/PS1dE9](+/-)/RAP(+/-) mice correlated with 30-40% increases in amyloid deposition by 9 months of age. CONCLUSIONS/SIGNIFICANCE: Partial reductions in the ER chaperone RAP enhance amyloid deposition in the APPswe/PS1dE9 model of Alzheimer amyloidosis. Partial reductions in RAP also affect the maturation of LRP and SorLA/LR11, which are each involved in several different aspects of APP processing and Abeta catabolism. Together, these findings suggest a central role for RAP in Alzheimer amyloidogenesis