IQRray, a new method for Affymetrix microarray quality control, and the homologous organ conservation score, a new benchmark method for quality control metrics.

MOTIVATION: Microarray results accumulated in public repositories are widely reused in meta-analytical studies and secondary databases. The quality of the data obtained with this technology varies from experiment to experiment, and an efficient method for quality assessment is necessary to ensure their reliability. RESULTS: The lack of a good benchmark has hampered evaluation of existing methods for quality control. In this study, we propose a new independent quality metric that is based on evolutionary conservation of expression profiles. We show, using 11 large organ-specific datasets, that IQRray, a new quality metrics developed by us, exhibits the highest correlation with this reference metric, among 14 metrics tested. IQRray outperforms other methods in identification of poor quality arrays in datasets composed of arrays from many independent experiments. In contrast, the performance of methods designed for detecting outliers in a single experiment like Normalized Unscaled Standard Error and Relative Log Expression was low because of the inability of these methods to detect datasets containing only low-quality arrays and because the scores cannot be directly compared between experiments. AVAILABILITY AND IMPLEMENTATION: The R implementation of IQRray is available at: ftp://lausanne.isb-sib.ch/pub/databases/Bgee/general/IQRray.R. CONTACT: Marta.Rosikiewicz@unil.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Is the thymus a target organ in infectious diseases?

The thymus is a central lymphoid organ, in wich T cell precursors differentiale and generate most of the so-called T cell reprtoire. Along with a variety of acute infectious diseases, we and others determined important changes in both microenvironmental and lymphoid compartments of the organ. For example, one major and common feature observed in acute viral, bacterial and parasitic diseases, is a depletion of cortical thymocytes, mostly those bearing the CD4-CD8 double positive phenotype. This occurs simmultaneously to the relative enrichment in medullary CD4 or CD8 single positive cells, expressing high densities of the CD3 complex. Additionally we noticed a variety of changes in the thymic microenvironment (and particularly is epithelial component), comprising abnormal location of thymic epithelial cell subsets as well has a denser Ia-bearing cellular network. Moreover, the extracellular matrix network was altered with an intralobular increase of basement membrane proteins that positively correlated with the degree of thymocyte death. Lastly, anti-thymic cell antibodies were detected in both human and animal models of infectious diseases, and in some of them a phenomenon of molecular mimicry could be evidenced. Taken together, the data receiwed herein clearly show that the thymus should be regarded as a target in infectious diseases.

The cave-like sense organ in the antennae of Triatominae bugs

In the second segment of the antennae of haematophagous reduviids an unusual cave-like organ is found the function os which was investigated in Triatoma infestans. the morphology of the organ makes it difficult to ascribe it to a mechno- or chemoreceptive function, but shows some characteristics shared with thermoreceptors of other animals. The electrical activity of sense cells was recorded in the presence of stimuli that evoke behavioural responses in this species, i.e. warm, CO2, lactic and butyric acids at different concentrations. The three compounds tested failed to evoke a response at all concentrations assayed. Only thermal stimulation evinced a clear modification in the electrical activity of the sense cells.Both the morphological and electrophysiological findings support a thermoreceptive finding, habitat selection and circadian synchronization.

Pelvic organ prolapse surgery with and without tension-free vaginal tape in women with occult or asymptomatic urodynamic stress incontinence: a randomised controlled trial.

INTRODUCTION: We set out to determine if insertion of a retropubic tension-free vaginal tape (TVT) sling at the time of pelvic organ prolapse surgery improves continence outcomes in women with pre-operative occult stress incontinence (OSI) or asymptomatic urodynamic stress incontinence (USI). METHODS: We conducted a randomised controlled study of prolapse surgery with or without a TVT midurethral sling. The pre- and post-operative assessment at 6 months included history, physical examination and urodynamic testing. Quality of life (QOL) and treatment success was assessed with the UDI-6 SF, IIQ-7 SF and a numerical success score. The primary outcome was symptomatic stress urinary incontinence (SUI) requiring continence surgery (TVT) at 6 months. Long-term follow-up continued to a minimum of 24 months. Secondary outcomes were quality of life parameters. RESULTS: Eighty women received prolapse surgery alone (n = 43) or prolapse surgery with concurrent TVT (n = 37). Six months following prolapse surgery 3 out of 43 (7 %) patients in the no TVT group requested sling surgery compared with 0 out of 37 (0 %) in the TVT group (ARR 7 % [95 %CI: 3 to 19 %], p = 0.11). After 24 months there was one further participant in the no TVT group who received a TVT for treatment of SUI compared with none in the TVT group (4 out of 43, 9.3 % versus 0 out of 37; ARR 9.3 % [95 %CI: -1 to 22 %], p = 0.06). Both groups showed improvement in QOL difference scores for within-group analysis, without difference between groups. CONCLUSION: These results support a policy that routine insertion of a sling in women with OSI at the time of prolapse repair is questionable and should be subject to shared decision-making between clinician and patient.

Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

INTRODUCTION: The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. METHODS: Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. RESULTS: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. CONCLUSIONS: Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.

Working Arrangements For The Welfare & Safeguarding of Child Victims of Human Trafficking - February 2011 (PDF 2.91MB)

Guidance issued by The Department of Health, Social Services & Public Safety & The Police Service for Northern Ireland

Mécanismes physiopathologiques impliqués dans la dysfonction d'organes au cours du sepsis [Pathophysiological mechanisms of organ dysfunction in sepsis].

Sepsis is defined as the systemic inflammatory response to an infection. The occurrence of organ dysfunction increases the severity of sepsis. Complex interactions between multiple immunomodulating mediators and various cell populations, activated secondarily to the initial infectious insult, promote the development of organ dysfunction in sepsis. Although septic organ dysfunction has long been considered as the end result of chaotic, uncontrolled and deregulated inflammatory cascades, it might instead represent an adaptive response to avoid the occurrence of irreversible tissue damage and end-organ injury. In this article, we review the major mechanisms involved in organ dysfunction during sepsis, and also present the concept of organ dysfunction as an adaptive response to the septic process.

Influenza vaccination and humoral alloimmunity in solid organ transplant recipients.

Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8 months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.

Evidence Base to Inform the Operational Arrangements for the Proposed Prescribing and Supply of Specialist Medicines

Executive Summary

New Local Body Arrangements for Nurses, Midwives and Health Visitors (PDF 44KB)

This paper proposes the creation of a new local body to support the initial and ongoing education, practice and performance of Nurses, Midwives and Health Visitors with the primary purpose of enhancing public protection. åÊ

Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.

As part of the ACuteTox project aimed at the development of non-animal testing strategies for predicting human acute oral toxicity, aggregating brain cell cultures (AGGR) were examined for their capability to detect organ-specific toxicity. Previous multicenter evaluations of in vitro cytotoxicity showed that some 20% of the tested chemicals exhibited significantly lower in vitro toxicity as expected from in vivo toxicity data. This was supposed to be due to toxicity at supracellular (organ or system) levels. To examine the capability of AGGR to alert for potential organ-specific toxicants, concentration-response studies were carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression levels of four selected genes. The lowest observed effect concentration (LOEC) determined for each chemical was compared with the IC20 reported for the 3T3/NRU cytotoxicity assay. A LOEC lower than IC20 by at least a factor of 5 was taken to alert for organ-specific toxicity. The results showed that the frequency of alerts increased with the level of toxicity observed in AGGR. Among the chemicals identified as alert were many compounds known for their organ-specific toxicity. These findings suggest that AGGR are suitable for the detection of organ-specific toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay, improve the predictive capacity of in vitro toxicity testing.