Microfluidic PCR devices with electrochemical detection of DNA

This research undertaken involved designing, fabricating and testing of a microfiuidic peR micro device with real-time electrochemical detection. The aim was to provide an analytical device which could lower the cost and the time taken for running DNA amplification. The later addition of automated sample handling and detection would thereby reduce the time taken and consequently the overall cost. The real-time electrochemical detection utilised an electrochemical assay for the detection of DNA invented by Molecular Sensing Ltd. It used a single strand ferrocenylated probe DNA molecule which could be detected with an electrochemical cell. The integration of an electrochemical cell was a key feature of this work, along with the immobilisation of the Taq polymerase at its working temperature. Taq polymerase enzyme and T7 polymerase enzyme were immobilised on to microspheres. Taq polymerase was immobilised in four ways and T7 polymerase was immobilised in only one method. After immobilisation the enzymes were unable to amplify DNA within peR experiments. Microfiuidic peR devices, which incorporate the above two features, were designed and fabricated. 3 basic ideas of devices were investigated, fiowthrough, straight line and cyclic triangle device. All the devices had fundamental problems which inhibited there ability to successfully amplify DNA. An electrochemical assay was used within a microfiuidic device with internal electrochemical detection, which utilised a filter to bring about sequence specific DNA detection. Using biotinylated complementary probe DNA attached to streptavidin coated beads to hybridise to the sample DNA. This device incorporated a solid phase extraction and clean up step as well as producing sequence specific DNA detection

Does group assessment impact BME attainment?

Assessment of student learning is fundamental in Higher Education (HE) reflecting academic standards and impacting on student satisfaction, position in league tables and graduate employment. Nonetheless, there is a BME (Black and Minority Ethnic) attainment gap, the difference in the proportion of BME and White students who attain a first class or 2.1 honours degree (even when controlled for prior attainment and entry profile), which is persistent across the HE sector. As assessment strategies play an essential role in determining degree attainment, we have reviewed the role of group assessment and whether this form of assessment specifically impacts on the BME attainment gap. Overall, this study provided evidence that assessed group work does not adversely impact BME students. In addition, the performance in BME/non-BME/mixed groups did not suggest any consistent difference, suggesting that the demographic composition of groups does not affect BME performance. Therefore, group work would appear to be an inclusive form of assessment that does not appear to lead or contribute to exacerbating the BME attainment gap

Preparing potential teachers for the transition from employment to teacher training: an evaluative case study of a Maths Enhancement Course

In response to a UK government drive to improve maths teaching in schools, the South West London Maths Enhancement Course (MEC) has been set up though collaboration between three Higher Education institutions (HEIs) to provide an efficient route for non maths graduates in employment to upgrade their subject knowledge and give a smooth transition into teacher training (PGCE). An evaluation of the scheme, measured against Teacher Development Agency (TDA) objectives and success criteria agreed by university staff, involved thematic analysis of focus group discussions and interviews with students and staff during both the MEC and PGCE courses. This has revealed a high level of satisfaction and success related to a number of underlying issues, particularly around student recruitment, curriculum design, peer support and staff collaboration. The model offers an example of practice transferable to a range of programmes aimed at supporting students in the transition between levels and institutions

Abstracts from the NIHR INVOLVE Conference 2017

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Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder