Allergic Responses Induced by a Fungal Biopesticide Metarhizium anisopliae and House Dust Mite Are Compared in a Mouse Model

Biopesticides can be effective in controlling their target pest. However, research regarding allergenicity and asthma development is limited. We compared the ability of fungal biopesticide Metarhizium anisopliae (MACA) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration at doubling doses (2.5–80 μg protein) 4X over a four-week period. Three days after the last exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The extracts' relative allergenicity was evaluated based on response robustness (lowest significant dose response compared to control (0 μg)). MACA induced a more robust serum total IgE response than HDM. However, in the antigen-specific IgE assay, a similar dose of both MACA and HDM was required to achieve the same response level. Our data suggest a threshold dose of MACA for allergy induction and that M. anisopliae may be similar to HDM in allergy induction potential

Development and validation of the brief esophageal dysphagia questionnaire

BackgroundEsophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy.Methods1638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split‐half reliability, ceiling and floor effects, and construct validity.Key ResultsThe BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split‐half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter‐item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant.Conclusions & InferencesThe BEDQ represents a rapid, reliable, and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction.Validated, rapid clinical assessment tools for esophageal dysphagia are lacking. The brief esophageal dysphagia questionnaire aims to gauge the severity and frequency of dysphagia with additional items to gauge food impaction. The BEDQ is a reliable and valid tool to assess esophageal dysphagia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135130/1/nmo12889.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135130/2/nmo12889_am.pd

Quantifying patient satisfaction with process metrics using a weighted bundle approach.

Background:Current patient satisfaction assessment results are delayed and obtained from select patient surveys. As a result, these assessments may not represent the experience of the entire patient population. This study developed a method to measure and evaluate all patients\u27 experiences while they are within the care episode and link it to processes within the organisation. Methods:Using the Six Sigma methodology, sites assembled diverse teams to categorise and analyse negative experience comments from patients to understand the drivers of dissatisfaction. These customer expectations lead to the development of the four components in the Patient Experience Bundle (PEB): communication, environment, basic needs/comfort and logistics. Individual process elements were ranked to create a numerical relationship between service and the needs expressed by the voice of the customer. Sites created surveys incorporating questions that focused on the bundle elements and measured daily bundle compliance. Graphical analysis and hypothesis testing enabled sites to determine key drivers of patient dissatisfaction within the bundle elements. Improvement strategies were developed and implemented to address the key drivers of patient dissatisfaction. Results:After implementing process improvements focused on issues identified by the PEB, bundle compliance improved from an average of 51% to an average of 82.5% and Press Ganey Likelihood to Recommend (PG LTR) scores improved from an average of 64.73% to an average 74.64%. The data demonstrated that the trends in improving PEB are followed by meaningful changes in PG LTR scores. Conclusion:This work is built on the identification of common elements of care that impact patient satisfaction and detailed mathematical analysis of the relationship between factors. Using the bundle concept, these improvement efforts maintain highly reliable processes to drive outcomes and provide real-time feedback on patient experience

Applying the Roofline Performance Model to the Intel Xeon Phi Knights Landing Processor

The Roofline Performance Model is a visually intuitive method used to bound the sustained peak floating-point performance of any given arithmetic kernel on any given processor architecture. In the Roofline, performance is nominally measured in floating-point operations per second as a function of arithmetic intensity (operations per byte of data). In this study we determine the Roofline for the Intel Knights Landing (KNL) processor, determining the sustained peak memory bandwidth and floating-point performance for all levels of the memory hierarchy, in all the different KNL cluster modes.We then determine arithmetic intensity and performance for a suite of application kernels being targeted for the KNL based supercomputer Cori, and make comparisons to current Intel Xeon processors. Cori is the National Energy Research Scientific Computing Center’s (NERSC) next generation supercomputer. Scheduled for deployment mid-2016, it will be one of the earliest and largest KNL deployments in the world

Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression

<p>Abstract</p> <p>Background</p> <p>Previous results showed that over-expression of the <it>WTH3 </it>gene in MDR cells reduced <it>MDR1 </it>gene expression and converted their resistance to sensitivity to various anticancer drugs. In addition, the <it>WTH3 </it>gene promoter was hypermethylated in the MCF7/AdrR cell line and primary drug resistant breast cancer epithelial cells. <it>WTH3 </it>was also found to be directly targeted and up regulated by the <it>p53 </it>gene. Furthermore, over expression of the <it>WTH3 </it>gene promoted the apoptotic phenotype in various host cells.</p> <p>Methods</p> <p>To further confirm <it>WTH3</it>'s drug resistant related characteristics, we recently employed the small hairpin RNA (shRNA) strategy to knockdown its expression in HEK293 cells. In addition, since the <it>WTH3 </it>promoter's p53-binding site was located in a CpG island that was targeted by methylation, we were interested in testing the possible effect this epigenetic modification had on the <it>p53 </it>transcription factor relative to <it>WTH3 </it>expression. To do so, the <it>in vitro </it>methylation method was utilized to examine the <it>p53 </it>transgene's influence on either the methylated or non-methylated <it>WTH3 </it>promoter.</p> <p>Results</p> <p>The results generated from the gene knockdown strategy showed that reduction of <it>WTH3 </it>expression increased <it>MDR1 </it>expression and elevated resistance to Doxorubicin as compared to the original control cells. Data produced from the methylation studies demonstrated that DNA methylation adversely affected the positive impact of <it>p53 </it>on <it>WTH3 </it>promoter activity.</p> <p>Conclusion</p> <p>Taken together, our studies provided further evidence that <it>WTH3 </it>played an important role in MDR development and revealed one of its transcription regulatory mechanisms, DNA methylation, which antagonized <it>p53</it>'s positive impact on <it>WTH3 </it>expression.</p

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling

We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1 degrees x1 degrees spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.Peer reviewe