MPHASYS: a mouse phenotype analysis system

<p>Abstract</p> <p>Background</p> <p>Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery.</p> <p>Results</p> <p>Here we introduce a Mouse Phenotype Analysis System (MPHASYS), a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd.</p> <p>Conclusion</p> <p>MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p

Long-term results of the neuroendoscopic management of colloid cysts of the third ventricle: a series of 90 cases

Contains fulltext : 98061.pdf (publisher's version ) (Closed access)BACKGROUND: The endoscopic removal of third ventricular colloid cysts has been developed as an alternative to microsurgical transcortical-transventricular and transcallosal approaches. OBJECTIVE: To examine the value of endoscopic technique by reviewing the large number of endoscopically treated patients with long-term follow-up in 2 neurosurgical centers. METHODS: A retrospective chart review was conducted for all patients admitted for resection of a third ventricular colloid cyst to the Radboud University Nijmegen Medical Centre (Nijmegen, The Netherlands) and the Hopital Henri Mondor (Paris, France) between 1994 and 2007. Both clinical and radiological symptoms and operative results were evaluated. RESULTS: Postdischarge clinical follow-up was available for 85 patients over a mean period of 4 years 3 months. Permanent morbidity occurred in 1 patient (persisting preoperative memory deficit). Follow-up imaging of 80 evaluable patients showed that total or nearly total cyst removal was possible in 46 individuals (57.5%). Residual cyst was present in 34 patients (42.5%), and 6 required repeated endoscopic surgery for symptomatic regrowth. Recurrent cysts were mainly seen within the first 2 years after surgery. CONCLUSION: It is debatable whether the higher numbers of recurrent or residual cysts can be justified by the slightly lower complication rates achieved with endoscopic removal. However, results have been improving over the years. Moreover, the modifications observed on control magnetic resonance images justify the need for regular control imaging for at least the first 2 years postoperatively

An Xpb Mouse Model for Combined Xeroderma Pigmentosum and Cockayne Syndrome Reveals Progeroid Features upon Further Attenuation of DNA Repair▿

Patients carrying mutations in the XPB helicase subunit of the basal transcription and nucleotide excision repair (NER) factor TFIIH display the combined cancer and developmental-progeroid disorder xeroderma pigmentosum/Cockayne syndrome (XPCS). Due to the dual transcription repair role of XPB and the absence of animal models, the underlying molecular mechanisms of XPBXPCS are largely uncharacterized. Here we show that severe alterations in Xpb cause embryonic lethality and that knock-in mice closely mimicking an XPCS patient-derived XPB mutation recapitulate the UV sensitivity typical for XP but fail to show overt CS features unless the DNA repair capacity is further challenged by crossings to the NER-deficient Xpa background. Interestingly, the XpbXPCS Xpa double mutants display a remarkable interanimal variance, which points to stochastic DNA damage accumulation as an important determinant of clinical diversity in NER syndromes. Furthermore, mice carrying the XpbXPCS mutation together with a point mutation in the second TFIIH helicase Xpd are healthy at birth but display neonatal lethality, indicating that transcription efficiency is sufficient to permit embryonal development even when both TFIIH helicases are crippled. The double-mutant cells exhibit sensitivity to oxidative stress, suggesting a role for endogenous DNA damage in the onset of XPB-associated CS

Should anterior pituitary function be tested during follow-up of all patients presenting at the emergency department because of traumatic brain injury?

Contains fulltext : 89243.pdf (publisher's version ) (Open Access)CONTEXT: A wide range (15-56%) of prevalences of anterior pituitary insufficiency are reported in patients after traumatic brain injury (TBI). However, different study populations, study designs, and diagnostic procedures were used. No data are available on emergency-department-based cohorts of TBI patients. OBJECTIVE: To assess the prevalence of pituitary dysfunction in an emergency-department-based cohort of TBI patients using strict endocrinological diagnostic criteria. METHODS: Of all the patients presenting in the emergency department with TBI over a 2-year period, 516 matched the inclusion criteria. One hundred and seven patients (77 with mild TBI and 30 with moderate/severe TBI) agreed to participate. They were screened for anterior pituitary insufficiency by GHRH-arginine testing, evaluation of fasting morning hormone levels (cortisol, TSH, free thyroxine, FSH, LH, and 17beta-estradiol or testosterone), and menstrual history 3-30 months after TBI. Abnormal screening results were defined as low peak GH to GHRH-arginine, or low levels of any of the end-organ hormones with low or normal pituitary hormone levels. Patients with abnormal screening results were extensively evaluated, including additional hormone provocation tests (insulin tolerance test, ACTH stimulation test, and repeated GHRH-arginine test) and assessment of free testosterone levels. RESULTS: Screening results were abnormal in 15 of 107 patients. In a subsequent extensive endocrine evaluation, anterior pituitary dysfunction was diagnosed in only one patient (partial hypocortisolism). CONCLUSION: By applying strict diagnostic criteria to an emergency-department-based cohort of TBI patients, it was shown that anterior pituitary dysfunction is rare (<1%). Routine pituitary screening in unselected patients after TBI is unlikely to be cost-effective.1 januari 201

From employment relations to consumption relations : balancing labor governance in global supply chains

Global supply chains are part of the corporate strategy of many multinational companies, often with adverse effects on labor conditions. While employment relations scholars focus on a production-oriented paradigm, revolving around interactions among employers, workers, and government, much of the activism motivating the development of private labor standards is based around companies' relations with their consumers. This article proposes an analytical framework conceptualizing the interface of employment relations and consumption relations within global supply chains, identifying four regimes of labor governance: governance gaps, collective bargaining, standards markets, and complementary regimes. Finally, we suggest a research agenda for examining the role of consumption relations in the changing nature of global labor governance