Generic protease detection technology for monitoring periodontal disease

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.<br/

Conserving tropical biodiversity via market forces and spatial targeting

The recent report from the Secretariat of the Convention on Biological Diversity [(2010) Global Biodiversity Outlook 3] acknowledges that ongoing biodiversity loss necessitates swift, radical action. Protecting undisturbed lands, although vital, is clearly insufficient, and the key role of unprotected, private land owned is being increasingly recognized. Seeking to avoid common assumptions of a social planner backed by government interventions, the present work focuses on the incentives of the individual landowner. We use detailed data to show that successful conservation on private land depends on three factors: conservation effectiveness (impact on target species), private costs (especially reductions in production), and private benefits (the extent to which conservation activities provide compensation, for example, by enhancing the value of remaining production). By examining the high-profile issue of palm-oil production in a major tropical biodiversity hotspot, we show that the levels of both conservation effectiveness and private costs are inherently spatial; varying the location of conservation activities can radically change both their effectiveness and private cost implications. We also use an economic choice experiment to show that consumers’ willingness to pay for conservation-grade palm-oil products has the potential to incentivize private producers sufficiently to engage in conservation activities, supporting vulnerable International Union for Conservation of Nature Red Listed species. However, these incentives vary according to the scale and efficiency of production and the extent to which conservation is targeted to optimize its cost-effectiveness. Our integrated, interdisciplinary approach shows how strategies to harness the power of the market can usefully complement existing—and to-date insufficient—approaches to conservation

Determining the probability of cyanobacterial blooms: the application of Bayesian networks in multiple lake systems

A Bayesian network model was developed to assess the combined influence of nutrient conditions and climate on the occurrence of cyanobacterial blooms within lakes of diverse hydrology and nutrient supply. Physicochemical, biological, and meteorological observations were collated from 20 lakes located at different latitudes and characterized by a range of sizes and trophic states. Using these data, we built a Bayesian network to (1) analyze the sensitivity of cyanobacterial bloom development to different environmental factors and (2) determine the probability that cyanobacterial blooms would occur. Blooms were classified in three categories of hazard (low, moderate, and high) based on cell abundances. The most important factors determining cyanobacterial bloom occurrence were water temperature, nutrient availability, and the ratio of mixing depth to euphotic depth. The probability of cyanobacterial blooms was evaluated under different combinations of total phosphorus and water temperature. The Bayesian network was then applied to quantify the probability of blooms under a future climate warming scenario. The probability of the "high hazardous" category of cyanobacterial blooms increased 5% in response to either an increase in water temperature of 0.8°C (initial water temperature above 24°C) or an increase in total phosphorus from 0.01 mg/L to 0.02 mg/L. Mesotrophic lakes were particularly vulnerable to warming. Reducing nutrient concentrations counteracts the increased cyanobacterial risk associated with higher temperatures

The role of treatment beliefs in the placebo effect

Treatment beliefs and related illness representations are important determinants of treatment uptake and adherence. This thesis explores whether these representations might also explain placebo effects. Within this thesis, a literature review outlines placebo mechanisms and summarises theory and research in relation to representations of treatment and illness. The empirical section that follows addresses three research questions identified by the review and explored in four studies. Study 1 was a randomised controlled trial using the cold pressor paradigm in healthy volunteers (n=167). This demonstrated that treatment beliefs predicted pain responses to two placebos described as pharmaceutical versus natural, consistent with the theoretical model of specific and general treatment beliefs. Study 2 involved patients (n=136) with symptoms of gastric-reflux, undergoing a diagnostic test. It showed that pain intensity, in response to oesophageal saline perfusion, could be significantly reduced by describing the saline as ‘therapeutic’ rather than as a ‘non-therapeutic’ component of the test procedure. Patients’ beliefs about their condition moderated the effect of framing on pain response to saline with more negative representations of gastric-reflux associated with lower therapeutic response. Studies 3 and 4 were conducted in parallel to explore whether placebo-related treatment beliefs could be modified by brief interventions designed to change beliefs. Study 3, an analogue study in health volunteers (n=222), found that a brief informational intervention designed to increase coherence between representations of asthma and its treatment did not influence treatment beliefs. In Study 4, placebo effects to cough induction in health volunteers (n= 62) were influenced by treatment beliefs (general pharmaceutical schema), but treatment beliefs were again, not influenced by the intervention used in Study 3. Despite their limitations the empirical studies suggest that treatment beliefs and illness representations are related to placebo effects, justifying further work to extend the scope and quality of this research

Optimizing future dark energy surveys for model selection goals

We demonstrate a methodology for optimizing the ability of future dark energy surveys to answer model selection questions, such as `Is acceleration due to a cosmological constant or a dynamical dark energy model?'. Model selection Figures of Merit are defined, exploiting the Bayes factor, and surveys optimized over their design parameter space via a Monte Carlo method. As a specific example we apply our methods to generic multi-fibre baryon acoustic oscillation spectroscopic surveys, comparable to that proposed for SuMIRe PFS, and present implementations based on the Savage-Dickey Density Ratio that are both accurate and practical for use in optimization. It is shown that whilst the optimal surveys using model selection agree with those found using the Dark Energy Task Force (DETF) Figure of Merit, they provide better informed flexibility of survey configuration and an absolute scale for performance; for example, we find survey configurations with close to optimal model selection performance despite their corresponding DETF Figure of Merit being at only 50% of its maximum. This Bayes factor approach allows us to interpret the survey configurations that will be good enough for the task at hand, vital especially when wanting to add extra science goals and in dealing with time restrictions or multiple probes within the same project.Comment: 12 pages, 16 figure

A Game of Spot the Difference: Librarians, Repository Managers, and Publishers

Many library publishing programs emerged from institutional repositories. This close relationship has led to the emergence of content platforms that are designed to operate under either use case, however, the missions and requirements of the two types of program differ. A repository for example, may be primarily concerned with the curation, preservation, and accessibility of their institution’s academic output whilst publishers must also concern themselves with external discoverability, search engine optimization, getting indexed in abstract databases and marketing their journals. In this session, you will hear from three successful library publishers who have embraced this external facing aspect of publishing. The overlaps and differences between repositories and publishers will be explored and the speakers will share their thoughts on how library publishers can best serve their patrons be disseminating work and helping researchers to meet funder mandates for open access and data management

"Random" gentamicin concentrations do not predict trough levels in neonates receiving once daily fixed dose regimens

BACKGROUND: Monitoring plasma gentamicin concentrations in neonates 24 hours after a once daily dose (4 mg/kg) often necessitates additional blood sampling. In adults a nomogram has been developed enabling evaluation of gentamicin doses by sampling concentrations with other blood tests, 4 – 16 hours after administration. We attempted to develop a similar nomogram for neonates. METHODS: In addition to standard 24 hour sampling to monitor trough concentrations, one additional "random" gentamicin concentration was measured in each of 50 neonates <4 days of age (median gestation 33 weeks [28–41]), when other blood samples were clinically necessary, 4 – 20 hours after gentamicin administration. 24 hour concentrations of >1 mg/L were considered high, and an indication to extend the dosing interval. RESULTS: Highest correlation (r(2 )= 0.51) of plasma gentamicin concentration against time (4 to 20 hours) was with logarithmic regression. A line drawn 0.5 mg/L below the true regression line resulted in all babies with 24 hr gentamicin concentrations >1 mg/L having the additional "random" test result above that line, i.e. 100% sensitivity for 24 hour concentrations>1 mg/L, though only 58% specificity. Having created the nomogram, 39 further babies (median gestation 34 weeks [28–41]), were studied and results tested against the nomogram. In this validation group, sensitivity of the nomogram for 24 hr concentrations >1 mg/L was 92%; specificity 14%, positive predictive value 66%, and negative predictive value 50%. Prematurity (≤ 37 weeks) was a more sensitive (94%) and specific (61%) indicator of high 24-hour concentrations. 62 (87%) of 71 preterm babies had high 24-hour concentrations. CONCLUSION: It was not possible to construct a nomogram to predict gentamicin concentrations at 24 hours in neonates with a variety of gestational ages. Dosage tailored to gestation with monitoring of trough concentrations remains management of choice

Beliefs about pharmaceutical medicines and natural remedies explain individual variation in placebo analgesia

This study examined whether placebo responses were predicted by a theoretical model of specific and general treatment beliefs. Using a randomised cross-over, experimental design (168 healthy individuals) we assessed whether responses to a cold pressor task were influenced by two placebo creams described as Pharmaceutical vs Natural origin. We assessed whether placebo responses were predicted by pre-treatment beliefs about the treatments (placebo) and by beliefs about the pain. The efficacy of both Pharmaceutical and Natural Placebos in reducing Pain Intensity was predicted by aspects of pain catastrophizing including Feelings of Helplessness (Pharmaceutical: B=0.03, p<0.01, Natural: B=0.02, p<0.05) and Magnification of Pain (Pharmaceutical: B=0.04, p<0.05, Natural: B=0.05, p<0.05) but also by pre-treatment Necessity beliefs (Pharmaceutical: B=0.21, p<0.01, Natural: B=0.16, p<0.05) and, for the Pharmaceutical condition, by more general beliefs in personal sensitivity to pharmaceuticals (B=0.14, p<0.05). Treatment Necessity beliefs also partially mediated the effects of Helplessness on placebo responses. Treatment Necessity beliefs for the Pharmaceutical Placebo were influenced by general pharmaceutical beliefs whereas Necessity beliefs for the Natural Placebo were informed by general background beliefs about holistic treatments. Our findings demonstrate that treatment beliefs influence the placebo effect suggesting that they may offer an additional approach for understanding the placebo effect. PERSPECTIVE: Placebo effects contribute to responses to active analgesics. Understanding how beliefs about different types of medicines influence placebo analgesia may be useful in understanding variations in treatment response. Using the cold-pressor paradigm we found that placebo analgesia is influenced by beliefs about natural remedies, pharmaceutical medicines and about pain

The quality of vital signs measurements and value preferences in electronic medical records varies by hospital, specialty, and patient demographics

We aimed to assess the frequency of value preferences in recording of vital signs in electronic healthcare records (EHRs) and associated patient and hospital factors. We used EHR data from Oxford University Hospitals, UK, between 01-January-2016 and 30-June-2019 and a maximum likelihood estimator to determine the prevalence of value preferences in measurements of systolic and diastolic blood pressure (SBP/DBP), heart rate (HR) (readings ending in zero), respiratory rate (multiples of 2 or 4), and temperature (readings of 36.0 °C). We used multivariable logistic regression to investigate associations between value preferences and patient age, sex, ethnicity, deprivation, comorbidities, calendar time, hour of day, days into admission, hospital, day of week and speciality. In 4,375,654 records from 135,173 patients, there was an excess of temperature readings of 36.0 °C above that expected from the underlying distribution that affected 11.3% (95% CI 10.6–12.1%) of measurements, i.e. these observations were likely inappropriately recorded as 36.0 °C instead of the true value. SBP, DBP and HR were rounded to the nearest 10 in 2.2% (1.4–2.8%) and 2.0% (1.3–5.1%) and 2.4% (1.7–3.1%) of measurements. RR was also more commonly recorded as multiples of 2. BP digit preference and an excess of temperature recordings of 36.0 °C were more common in older and male patients, as length of stay increased, following a previous normal set of vital signs and typically more common in medical vs. surgical specialities. Differences were seen between hospitals, however, digit preference reduced over calendar time. Vital signs may not always be accurately documented, and this may vary by patient groups and hospital settings. Allowances and adjustments may be needed in delivering care to patients and in observational analyses and predictive tools using these factors as outcomes or exposures