AuNP-Agglomerated monoliths in pipette tips for lectin affinity extraction of glycoproteins

• To in situ fabricate ethylene dimethacrylate porous polymer monoliths within the confines of a commercial 20 μL polypropylene pipette tips. • To enhance the monolith surface area by immobilising AuNPs and then functionalise the AuNPs with ECL lectin for selective extraction of galactosylated proteins from complex media

The problem of the end: A sociological study of the management of apocalyptic faith at Kensington Temple, a London Pentecostal church, at the turn of the millennium.

This thesis is a sociological study of the management of apocalyptic belief in Kensington Temple, a Pentecostal church in London, in the years 1997-2000. Apocalyptic or millenarian beliefs, in which the supernatural end of the world lies just around the corner, have often been explained in terms of material deprivation or psychological disturbance. This study shows how members of a church with an apocalyptic tradition reconciled the doctrine of the Second Coming with their daily lives. It rejects the idea that there is a simple cause of apocalyptic beliefs, focussing instead on millenarianism as a form of rhetoric whose prophecies are constantly overtaken by events - a phenomenon referred to as "the Problem of the End". Throughout history, members of apocalyptic religions have modified millenarian theology until its social costs are outweighed by its benefits. In practice, this has often meant the replacement of risky, time-specific predictions of Doomsday (predictive millenarianism) by apocalyptic narratives whose function is to account for features of the contemporary world (explanatory millenarianism). The data from Kensington Temple, which includes the results of a survey of 2,973 worshippers, points in this direction. It shows that worshippers assigned a low priority to the concept of the "End Times", subjecting it to the same rational scrutiny that they applied to other spiritual claims. Almost none of them expected the year 2000 to bring the Second Coming of Christ, though it did serve as a deadline for an unsuccessful plan to create a network of 2,000 church groups that carried eschatological overtones. The thesis concludes that the fragmentation of religious meaning in modern society undermines the plausibility of apocalyptic prophecies, at least in the industrialised West; literal belief in millenarian doctrines is a casualty of secularisation

Why do drivers become safer over the first three months of driving? A longitudinal qualitative study

Drivers are at high crash risk when they begin independent driving, with liability decreasing steeply over the first three months. Their behavioural development, and other changes underlying improved safety are not well understood. We adopted an innovative longitudinal qualitative design, with thirteen newly qualified drivers completing a total of 36 semi-structured interviews, one, two and three months after acquiring a full UK driving license. The interviews probed high-risk factors for new drivers, as well as allowing space for generating novel road safety issues. Analysis adopted a dual deductive and inductive interpretative thematic approach, identifying three super-ordinate themes: (1) Improvements in car control skills and situation awareness; (2) A reduction in the thrill of taking risks when driving against a background of generally increasing driving speed; (3) Early concerns about their social status in the eyes of other road users during the early stages of driving, which may put pressure on them to drive faster than they felt comfortable with. The study provides important new leads towards understanding how novice driving becomes safer over the first few months of driving, including how well-studied concepts of driving skill and style may change during development of independent driving, and a focus on the less rigorously studied concept of social status

Why are newly qualified motorists at high crash risk? Modelling driving behaviours across the first six months of driving

Objective: Novice driver crash risk diminishes steeply over the first few months of driving. We explore the characteristics of driving over this period to identify behaviours that might underlie this change in risk. Methods: We conducted a cross-sectional study of 1456 UK drivers aged 17-21 within six months of gaining their licence. We examined how various forms of driving exposure, such as weekly mileage and driving at night, were related to duration of licencing. We explored the factor structure of the Early Driving Development Questionnaire (EDD-Q); a new instrument designed to measure safety relevant attitudes and behaviours in recently qualified drivers. We examined the relationship of the derived factors to licence duration. Results: There was little evidence that greater exposure to risky driving situations was more common in those with shorter licence durations. Exploratory and Confirmatory Factor Analyses identified EDD-Q factors measuring risky style (12 items), skill deficiencies (8 items) and driving confidence (4 items). Licence duration was positively correlated with both risky style and confidence, with these relationships stronger for older novices. Licence duration was also negatively related to skill deficiencies (i.e., positively correlated with perceived driving skill development): this relationship was stronger in younger novices. Conclusions: The negative correlation between license duration and skill deficiencies is consistent with the observation of decreasing novice crash involvement as experience is gained. The EDD-Q offers a new brief measure of aberrant driving that is specifically tailored for newly qualified drivers

Efficacy and acceptability of pharmacological and non-pharmacological interventions for non-specific chronic low back pain:a protocol for a systematic review and network meta-analysis

Background: Despite the enormous financial and humanistic burden of chronic low back pain (CLBP), there is little consensus on what constitutes the best treatment options from a multitude of competing interventions. The objective of this network meta-analysis (NMA) is to determine the relative efficacy and acceptability of primary care treatments for non-specific CLBP, with the overarching aim of providing a comprehensive evidence base for informing treatment decisions. Methods: We will perform a systematic search to identify randomised controlled trials of interventions endorsed in primary care guidelines for the treatment of non-specific CLBP in adults. Information sources searched will include major bibliographic databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO and LILACS) and clinical trial registries. Our primary outcomes will be patient-reported pain ratings and treatment acceptability (all-cause discontinuation), and secondary outcomes will be functional ability, quality of life and patient/physician ratings of overall improvement. A hierarchical Bayesian class-based NMA will be performed to determine the relative effects of different classes of pharmacological (NSAIDs, opioids, paracetamol, anti-depressants, muscle relaxants) and non- pharmacological (exercise, patient education, manual therapies, psychological therapy, multidisciplinary approaches, massage, acupuncture, mindfulness) interventions and individual treatments within a class (e.g. NSAIDs: diclofenac, ibuprofen, naproxen). We will conduct risk of bias assessments and threshold analysis to assess the robustness of the findings to potential bias. We will compute the effect of different interventions relative to placebo/no treatment for both short- and long-term efficacy and acceptability. Discussion: While many factors are important in selecting an appropriate intervention for an individual patient, evidence for the analgesic effects and acceptability of a treatment are key factors in guiding this selection. Thus, this NMA will provide an important source of evidence to inform treatment decisions and future clinical guidelines

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

Author version made available in accordance with publisher policy.Abstract Background The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett’s esophagus. Methods Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett’s esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett’s esophagus (Mann-Whitney U test, P<0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett’s esophagus (linear regression, P0.7, P<0.05). A multi-biomarker panel (RNU6-1/miR- 16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR- 30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC=0.99, 95 % CI 0.96–1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett’s esophagus. Conclusions This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma

Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study

Author version made available following 12 month embargo from date of publication (27 March 2015) in accordance with publisher copyright policy.Purpose Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Methods Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45–50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Results Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. Conclusions This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted

Driving impairment and crash risk in Parkinson disease

OBJECTIVES: To provide the best possible evidence base for guiding driving decisions in Parkinson disease (PD), we performed a meta-analysis comparing patients with PD to healthy controls (HCs) on naturalistic, on-the-road, and simulator driving outcomes. METHODS: Seven major databases were systematically searched (to January 2018) for studies comparing patients with PD to HCs on overall driving performance, with data analyzed using random-effects meta-analysis. RESULTS: Fifty studies comprising 5,410 participants (PD = 1,955, HC = 3,455) met eligibility criteria. Analysis found the odds of on-the-road test failure were 6.16 (95% confidence interval [CI] 3.79-10.03) times higher and the odds of simulator crashes 2.63 (95% CI 1.64-4.22) times higher for people with PD, with poorer overall driving ratings also observed (standardized mean differences from 0.50 to 0.67). However, self-reported real-life crash involvement did not differ between people with PD and HCs (odds ratio = 0.84, 95% CI 0.57-1.23, p = 0.38). Findings remained unchanged after accounting for any differences in age, sex, and driving exposure, and no moderating influence of disease severity was found. CONCLUSIONS: Our findings provide persuasive evidence for substantive driving impairment in PD, but offer little support for mandated PD-specific relicensure based on self-reported crash data alone, and highlight the need for objective measures of crash involvement

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy