How can industry engage with the NICRN?

The Northern Ireland Clinical Research Network (NICRN) undertakes research in a range of medical fields. The NICRN is part of a UK-wide initiative to provide opportunities for patients and clinicians to participate in high-quality clinical research. This leaflet is targeted towards commercial partners who may wish to conduct clinical trials within Health and Social Care (HSC). The NICRN offers a range of supports for commercial partners, which allow clinical trials to get underway quickly and ensure they run smoothly.� Increasing opportunities for HSC service users to participate in clinical research and trials has the potential to bring benefits for the patients themselves and longer-term benefits to the HSC system in Northern Ireland as a whole.

Germline transformation of Aedes fluviatilis (Diptera:Culicidae) with the piggyBac transposable element

The technique to generate transgenic mosquitoes requires adaptation for each target species because of aspects related to species biology, sensitivity to manipulation and rearing conditions. Here we tested different parameters on the microinjection procedure in order to obtain a transgenic Neotropical mosquito species. By using a transposon-based strategy we were able to successfully transform Aedes fluviatilis (Lutz), which can be used as an avian malaria model. These results demonstrate the usefulness of the piggyBac transposable element as a transformation vector for Neotropical mosquito species and opens up new research frontiers for South American mosquito vectors.

Multimedia materials for education, training, and advocacy in international health: experiences with the Schistosomiasis Control Initiative CD-ROM

We describe an innovative use of multimedia materials to support training and advocacy within a schistosomiasis control programme. The Schistosomiasis Control Initiative (SCI) at Imperial College London works with selected sub-Saharan African countries to develop schistosomiasis control programmes. Two elements of the SCI programme were supported by multimedia materials developed at the Wellcome Trust in collaboration with the SCI: (1) training of programme managers, district health officers, and those delivering practical elements of the programme; and (2) advocacy targeted at decision-makers and donors. Evaluation of the materials revealed high reported ratings for both user satisfaction and impact from use of the product. From this experience we draw out several general messages about development of multimedia materials and how these will play a growing future role in promoting training within international health.

Independent relations of left ventricular structure with the 24-hour urinary excretion of sodium and aldosterone.

Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa(prox)) and distal (RNa(dist)) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (+2.48 g/m(2); P=0.005) and aldosterone (+2.63 g/m(2); P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12 mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070 mm; P=0.28). Higher RNa(dist) was associated with lower relative wall thickness (-0.81x10(-2), P=0.017), because of opposite trends in LVID (+0.33 mm; P=0.13) and MWT (-0.130 mm; P=0.040). LVMI was not associated with PRA or RNa(prox.) In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

Pathway analysis of glioblastoma tissue after preoperative treatment with the EGFR tyrosine kinase inhibitor gefitinib--a phase II trial.

Amplification of the epidermal growth factor receptor (EGFR) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we aimed at investigating the molecular effects of the tyrosine kinase inhibitor gefitinib on the EGFR signaling pathway in human glioblastoma. Twenty-two patients selected for reoperation of recurrent glioblastoma were treated within a phase II trial for 5 days with 500 mg gefitinib before surgery followed by postoperative gefitinib until recurrence. Resected glioblastoma tissues exhibited high concentrations of gefitinib (median, 4.1 μg/g), 20 times higher than respective plasma. EGFR-pathway activity was evaluated with phosphorylation-specific assays. The EGFR was efficiently dephosphorylated in treated patients as compared to a control cohort of 12 patients. However, no significant effect on 12 pathway constituents was detected. In contrast, in vitro treatment of a glioblastoma cell line, BS-153, with endogenous EGFRwt amplification and EGFRvIII expression resulted not only in dephosphorylation of the EGFR, but also of key regulators in the pathway such as AKT. Treating established xenografts of the same cell line as an in vivo model showed dephosphorylation of the EGFR without affecting downstream signal transductors, similar to the human glioblastoma. Taken together, gefitinib reaches high concentrations in the tumor tissue and efficiently dephosphorylates its target. However, regulation of downstream signal transducers in the EGFR pathway seems to be dominated by regulatory circuits independent of EGFR phosphorylation.

Pédiatrie. 5. Le partage de l'information médicale en 2012 [Pediatrics. Sharing of the medical letter with the patient].

Some paediatrics centres routinely send the medical consultation letter not only to the primary or referring physician but to the patient and his/her family as well. This way of sharing medical information is appreciated not only by the patients themselves but also by a majority of physicians.

Proposing a 'Consent Commons' in open education - balancing the desire for openness with the rights of people to refuse or withdraw from participation

A new 'Consent Commons' licensing framework is proposed, complementing Creative Commons, to clarify the permissions given for using and reusing clinical and non-clinical digital recordings of people (patients and non-patients) for educational purposes. Consent Commons is a sophisticated expression of ethically based 'digital professionalism', which recognises the rights of patients, carers, their families, teachers, clinicians, students and members of the public to have some say in how their digital recordings are used (including refusing or withdrawing their consent), and is necessary in order to ensure the long term sustainability of teaching materials, including Open Educational Resources (OER). Consent Commons can ameliorate uncertainty about the status of educational resources depicting people, and protect institutions from legal risk by developing robust and sophisticated policies and promoting best practice in managing their information.

Capturing and Organizing Prior Student Learning with the OCW Backpack

The purpose of this paper is to present an approach for students to have non-traditional learning assessed for credit and introduce a tool that facilitates this process. The OCW Backpack system can connect self-learners with KNEXT assessment services to obtain college credit for prior learning. An ex post facto study based on historical data collected over the past two years at Kaplan University (KU) is presented to validate the portfolio assessment process. Cumulative GPA was compared for students who received experiential credit for learning derived from personal or professional experience with a matched sample of students with no experiential learning credits. The study found that students who received experiential credits perform better than the matched sample students on GPA. The findings validate the KU portfolio assessment process. Additionally, the results support the capability of the OCW Backpack to capture the critical information necessary to evaluate non-traditional learning for university credit.

The redox potential interferes with the expression of laminin binding molecules in Bacteroides fragilis

The Bacteroides fragilis ATCC strain was grown in a synthetic media with contrasting redox potential (Eh) levels [reduced (-60 mV) or oxidised (+100mV)] and their adhesion capacity to extracellular matrix components was evaluated. The strain was capable of adhering to laminin, fibronectin, fibronectin + heparan sulphate and heparan sulphate. A stronger adherence to laminin after growing the strain under oxidising conditions was verified. Electron microscopy using ruthenium red showed a heterogeneous population under this condition. Dot-blotting analyses confirmed stronger laminin recognition by outer membrane proteins of cells cultured at a higher Eh. Using a laminin affinity column, several putative laminin binding proteins obtained from the cultures kept under oxidising (60 kDa, 36 kDa, 25 kDa and 15 kDa) and reducing (60 kDa) conditions could be detected. Our results show that the expression of B. fragilis surface components that recognise laminin are influenced by Eh variations.

Hepatitis C among former athletes: association with the use of injectable stimulants in the past

This study was performed with the purpose of testing the hypothesis that the high prevalence of hepatitis C among former athletes is associated with their past use of injectable stimulants. The study involved the participation of 208 former professional and amateur soccer and basketball players from the region of Ribeirão Preto, Brazil, who answered a questionnaire regarding their exposure to risk factors, including the use of injectable stimulants in the time they were engaged in sporting activities. ELISA tests were used to detect infection by the hepatitis C virus, and confirmed with PCR and genotyping for the positive cases. It was observed that the former use of injectable stimulants was a practice disseminated among the participants (24.5%), reaching 50.8% in the professionals. The overall prevalence for hepatitis C was 7.2%, with values of 11% among professionals and 5.5% among amateurs. In both categories, the presence of infection was markedly higher among those who admitted past use of injectable stimulants when compared to those who denied such practice (36% and 0.8% among amateurs; 21.9% and 0% among professionals, respectively). Multivariate analysis showed that the use of those substances was the only variable associated with the risk of hepatitis C. This confirms previous observations, performed with reduced sample sizes and without comparison groups, which indicated that the use of injectable vitamins was a risk factor of hepatitis C among former athletes.

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

The immune response is crucial for protection against disease; however, immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. Several studies have evaluated the cellular and humoral immune responses in chagasic patients in an attempt to correlate immunological findings with clinical forms of Chagas disease. Moreover, immunoglobulins and cytokines are important for parasitic control and are involved in lesion genesis. Here, cytokine and IgG isotype production were studied, using total epimastigote antigen on sera of chagasic patients with indeterminate (IND, n = 27) and cardiac (CARD, n = 16) forms of the disease. Samples from normal, uninfected individuals (NI, n = 30) were use as controls. The results showed that sera from both IND and CARD patients contained higher levels of Trypanosoma cruzi-specific IgG1 (IgG1) antibodies than sera from NI. No difference in IgG2 production levels was observed between NI, IND and CARD patients, nor was a difference in IL-10 and IFN-³ production detected in the sera of IND, CARD and NI patients. However, IND patients displayed a positive correlation between IL-10 and IFN-³ levels in serum, while CARD patients showed no such correlation, indicating an uncontrolled inflammatory response in CARD patients. These findings support the hypothesis that a lack of efficient regulation between IFN-³ and IL-10 productions in CARD patients may lead to cardiac immunopathology.

New records of calyptrate dipterans (Fanniidae, Muscidae and Sarcophagidae) associated with the decomposition of domestic pigs in Brazil

The calyptrate dipterans are the most important decomposers of human cadavers. Knowledge of their species and distribution are of great importance to forensic entomology, especially because of the enormous diversity in Brazil. Carcasses of domestic pigs (Sus scrofa, L) were the experimental models used to attract calyptrates of forensic interest during the winters of 2006 and 2007 and the summers of 2006 and 2008. A total of 24,423 specimens from 44 species were collected (19 Muscidae, 2 Fanniidae and 23 Sarcophagidae), three of which were new records of occurrence and 20 of which were new forensic records for the state of Rio de Janeiro. Fourteen of these species were newly identified as forensically important in Brazil.

Biological activity of the mite Sancassania sp. (Acari: Acaridae) from bat guano associated with the pathogenic fungus Histoplasma capsulatum

Mites and the mammal pathogenic fungus Histoplasma capsulatum are the major components of bat guano microbiota. Interactions between mites and H. capsulatum were evaluated under laboratory conditions. Acarid mites, mainly Sancassania sp., were the most abundant microarthropod in the sampled guano of the Mexican bat Tadarida brasiliensis mexicana and, based on its morphology, Sancassania sp. was similar to the cosmopolitan species Sancassania sphaerogaster. The mycophagous and vectoring activities of this mite were tested for H. capsulatum and two other fungal species, Sporothrix schenckii (pathogenic) and Aspergillus sclerotiorum (non-pathogenic). S. ca. sphaerogaster was able to reproduce in H. capsulatum and S. schenckii colonies, multiplying in great numbers under controlled fungal mycelial-phase culture conditions. H. capsulatum colonies were completely destroyed after 14 days of in vitro interaction with mites. In contrast, S. ca. sphaerogaster did not reproduce in A. sclerotiorum cultures. S. ca. sphaerogaster was found vectoring H. capsulatum, but not the two other fungal species studied.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-γ, TNF-α and TGF-β, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, γ-glutamil transferase (γ-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-α (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), γ-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.