On the organic carbon maximum on the continental slope of the eastern Arabian Sea

The sedimentary organic carbon maximum on the continental slope off western India is widely believed to be due to the preferential preservation of deposited organic matter at water depths where the intense oxygen minimum intersects the sea floor. This region is considered to constitute one of the modern analogues for the environment of formation of organic-rich sedimentary facies that are common in the geological record. We critically examine the hypothesis that the oxygen minimum in the eastern Arabian Sea is the site of enhanced organic matter accumulation and preservation using analyses of suites of samples with wide geographical coverage along this margin. Organic carbon and nitrogen reach maximum concentrations between 200 and 1600 m depth, whereas the lowest dissolved oxygen contents in the oxygen minimum lie between 200 and 800 m depth. The Corganic/N ratios and the δ13Corganic values show that the organic matter is overwhelmingly marine, and Rock-Eval pyrolysis data demonstrate that the hydrogen indices of the sediments are similar in the sediments accumulating within and outside the oxygen minimum. Thus, the organic carbon maximum extends over a larger depth range than the oxygen minimum (as is also evident on some other slopes), and there is no evidence for preferential preservation of the organic matter within the oxygen minimum. The distribution of organic matter on the western Indian continental margin is controlled by (1) variations in supply (decreasing westward away from the centers of coastal upwelling and also decreasing with increasing water depth), (2) dilution by other sedimentary components, and (3) the texture of the sediments (coarser-grained sediments having lower carbon contents), which is controlled in turn by sediment supply and reworking. The evidence available suggests that the organic carbon maximum on this slope is not related to the position of the oxygen minimum and, consequently, that oxygen minima cannot be used to explain the distribution of organic carbon at intermediate palaeodepths in the geological record

Automated mediator synthesis: combining behavioural and ontological reasoning

Software systems are increasingly composed of independently developed heterogeneous components. To ensure interoperability, mediators are needed that coordinate actions and translate exchanged messages between the components. We present a technique for automated synthesis of mediators, by means of a quotient operator, that is based on behavioural models of the components and an ontological model of the data domain. By not requiring a specification of the composed system, the method supports both off-line and run-time synthesis. The obtained mediator is the most general component that ensures freedom of both communication mismatches and deadlock in the composition. Validation of the approach is given by implementation of a prototype tool, while applicability is illustrated on heterogeneous holiday booking components

A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers

Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

The cancer vaccine 105AD7 is an anti-idiotypic monoclonal antibody that mimics the tumour-associated antigen 791T/gp72 (CD55, Decay Accelerating Factor) on colorectal cancer cells. Phase I studies in patients with advanced disease confirmed that 105AD7 is non-toxic, and that T cell responses could be generated. A prospective, randomized, double-blind, placebo-controlled survival study in patients with advanced colorectal cancer was performed. 162 patients were enrolled between April 1994 and October 1996. Patients attended at trial entry, and at 6 and 12 weeks, where they received 105AD7 or placebo. Study groups were comparable in terms of patient demographics, and time from diagnosis of advanced colorectal cancer (277.1 v 278.6 days). Baseline disease was similar, with 50% of patients having malignancy in at least 2 anatomic sites. Compliance with treatment was poor, with only 50% of patients receiving 3 planned vaccinations. Median survival from randomization date was 124 and 184 days in 105AD7 and placebo arms respectively (P = 0.38), and 456 and 486 days from the date of diagnosis of advanced disease (P = 0.82). 105AD7 vaccination does not prolong survival in patients with advanced colorectal cancer. The reasons for lack of efficacy are unclear, but may reflect the high tumour burden in the patient population, and poor compliance with immunization. Further vaccine studies should concentrate on patients with minimal residual disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

Changing knowledge, attitudes and behaviours towards cytomegalovirus in pregnancy through film-based antenatal education: a feasibility randomised controlled trial of a digital educational intervention

Background Congenital cytomegalovirus (CMV) is the most common congenital infection globally, however information about CMV is not routinely included in antenatal education in the United Kingdom. This feasibility study aimed to gather the essential data needed to design and power a large randomised controlled trial (RCT) to investigate the efficacy of a digital intervention in reducing the risk of CMV acquisition in pregnancy. In order to do this, we carried out a single-centre RCT, which explored the knowledge, attitudes and risk reduction behaviours in women in the intervention and treatment as usual groups, pre- and post-intervention. Methods CMV seronegative women living with a child less than four years old, receiving antenatal care at a single UK tertiary centre, were randomised to the digital intervention or ‘treatment as usual’ groups. Participants completed questionnaires before the digital intervention and after and at 34 gestational weeks, and responses within groups and between groups were compared using tailored randomisation tests. CMV serology was tested in the first trimester and at the end of pregnancy. Results Of the 878 women screened, 865 samples were analysed with 43% (n = 372) being CMV seronegative and therefore eligible to take part in the RCT; of these, 103 (27.7%) women were enrolled and 87 (84%) of these completed the study. Most participants (n = 66; 64%) were unfamiliar with CMV at enrolment, however at 34 gestational weeks, women in the intervention group (n = 51) were more knowledgeable about CMV compared to the treatment as usual group (n = 52) and reported engaging in activities that may increase the risk of CMV transmission less frequently. The digital intervention was highly acceptable to pregnant women. Overall, four participants seroconverted over the course of the study: two from each study group. Conclusions A large multi-centre RCT investigating the efficacy of a CMV digital intervention is feasible in the United Kingdom; this study has generated essential data upon which to power such a study. This single-centre feasibility RCT demonstrates that a digital educational intervention is associated with increase in knowledge about CMV and can result in behaviour change which may reduce the risk of CMV acquisition in pregnancy

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation