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

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

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction

<p>Abstract</p> <p>Background</p> <p>Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction</p> <p>Methods</p> <p>The study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.</p

Prognostic significance of third ventricle blood volume in intracerebral haemorrhage with severe ventricular involvement

Background and purpose: Intraventricular haemorrhage (IVH) is an independent predictor of poor outcome in spontaneous intracerebral haemorrhage (ICH). Larger IVH volume and increasing number of affected ventricles have been associated with worse prognosis, however, little is known about the prognostic value of blood volume in the different parts of the ventricular system. Therefore, the correlation of IVH volume in the third, fourth and lateral ventricles with outcome in patients with ICH and severe IVH, treated with intraventricular fibrinolysis (IVF), was investigated. Methods: Patients with ICH <40 ml, severe IVH and acute hydrocephalus were treated with IVF. The course of IVH volume for each ventricle was measured by CT based volumetry. Outcome at 90 days was assessed by a telephone follow-up survey and correlated with initial IVH volume. Results: 50 patients aged 62.5±10.3 years with spontaneous ICH (12.5±10.8 ml) and severe IVH (33.5±25 ml) were included. Clearance of the third and fourth ventricle from blood occurred after 3±1.9 days. Initial IVH volume in the third ventricle (3.8±3.3 ml) was predictive for poor outcome (OR 2.6 per ml, p=0.02). Correlation between larger IVH volume in the fourth ventricle and poor outcome showed a trend towards significance (p=0.07). Total IVH volume and lateral ventricle IVH volume were not correlated with outcome. Conclusion: Despite rapid clot removal, initial IVH volume in the third ventricle was a strong and independent negative predictor. This is possibly explained by irreversible damage of brainstem structures by the initial mass effect of IVH