A step-wise approach to developing indicators to compare the performance of maternity units using hospital administrative data.

Hospital administrative data are attractive for comparing performance of maternity units because of their often large sample sizes, lack of selection bias and the relatively low costs of accessing these data compared with conducting primary data collection. However, using administrative data to develop indicators can also present challenges including varying data quality, the limited detail on clinical risk factors and a lack of structural and user experience measures. This review illustrates how to develop performance indicators for maternity units using hospital administrative data, including methods to address the challenges that administrative data pose. TWEETABLE ABSTRACT: How to develop maternity indicators from administrative data

Evaluation of effectiveness of instruction and study habits in two consecutive clinical semesters of the medical curriculum munich (MeCuM) reveals the need for more time for self study and higher frequency of assessment

<p>Abstract</p> <p>Background</p> <p>Seven years after implementing a new curriculum an evaluation was performed to explore possibilities for improvements.</p> <p>Purposes: To analyze students' study habits in relation to exam frequency and to evaluate effectiveness of instruction.</p> <p>Methods</p> <p>Time spent on self study (TSS) and the quantity of instruction (QI) was assessed during the internal medicine and the surgical semester. Students and faculty members were asked about study habits and their evaluation of the current curriculum.</p> <p>Results</p> <p>The TSS/QI ratio as a measure of effectiveness of instruction ranges mainly below 1.0 and rises only prior to exams. Students and teachers prefer to have multiple smaller exams over the course of the semester. Furthermore, students wish to have more time for self-guided study.</p> <p>Conclusions</p> <p>The TSS/QI ratio is predominantly below the aspired value of 1.0. Furthermore, the TSS/QI ratio is positively related to test frequency. We therefore propose a reduction of compulsory lessons and an increase in test frequency.</p

Altered branching patterns of Purkinje cells in mouse model for cortical development disorder

Disrupted cortical cytoarchitecture in cerebellum is a typical pathology in reeler. Particularly interesting are structural problems at the cellular level: dendritic morphology has important functional implication in signal processing. Here we describe a combinatorial imaging method of synchrotron X-ray microtomography with Golgi staining, which can deliver 3-dimensional(3-D) micro-architectures of Purkinje cell(PC) dendrites, and give access to quantitative information in 3-D geometry. In reeler, we visualized in 3-D geometry the shape alterations of planar PC dendrites (i.e., abnormal 3-D arborization). Despite these alterations, the 3-D quantitative analysis of the branching patterns showed no significant changes of the 77 ± 8° branch angle, whereas the branch segment length strongly increased with large fluctuations, comparing to control. The 3-D fractal dimension of the PCs decreased from 1.723 to 1.254, indicating a significant reduction of dendritic complexity. This study provides insights into etiologies and further potential treatment options for lissencephaly and various neurodevelopmental disorders

Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

<p>Abstract</p> <p>Background</p> <p>To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.</p> <p>Methods</p> <p>A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).</p> <p>Results</p> <p>Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.</p> <p>Conclusions</p> <p>PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.</p

MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1214–224 epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design

Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy. Methods. To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks. Results. A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET. Conclusion. In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity. Trial registration. The study is registered as NCT00221052 in clinicaltrials.gov database. © 2010 van Erk et al; licensee BioMed Central Ltd

A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes.

Understanding the dynamics of endogenous protein-protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have previously developed a method termed RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins). Here, we present a quantitative multiplexed method (qPLEX-RIME), which integrates RIME with isobaric labelling and tribrid mass spectrometry for the study of protein interactome dynamics in a quantitative fashion with increased sensitivity. Using the qPLEX-RIME method, we delineate the temporal changes of the Estrogen Receptor alpha (ERα) interactome in breast cancer cells treated with 4-hydroxytamoxifen. Furthermore, we identify endogenous ERα-associated proteins in human Patient-Derived Xenograft tumours and in primary human breast cancer clinical tissue. Our results demonstrate that the combination of RIME with isobaric labelling offers a powerful tool for the in-depth and quantitative characterisation of protein interactome dynamics, which is applicable to clinical samples