Continuous correlated beta processes

In this paper we consider a (possibly continuous) space of Bernoulli experiments. We assume that the Bernoulli distributions are correlated. All evidence data comes in the form of successful or failed experiments at different points. Current state-ofthe-art methods for expressing a distribution over a continuum of Bernoulli distributions use logistic Gaussian processes or Gaussian copula processes. However, both of these require computationally expensive matrix operations (cubic in the general case). We introduce a more intuitive approach, directly correlating beta distributions by sharing evidence between them according to a kernel function, an approach which has linear time complexity. The approach can easily be extended to multiple outcomes, giving a continuous correlated Dirichlet process, and can be used for both classification and learning the actual probabilities of the Bernoulli distributions. We show results for a number of data sets, as well as a case-study where a mixture of continuous beta processes is used as part of an automated stroke rehabilitation system.

From patent to patient: analysing access to innovative cancer drugs.

Analysis of cancer drugs licensed through the European Medicines Agency (EMA) in 2000-2016 shows that the number of authorisations increased over that timeframe. The median number of licensed drugs each year rose from six for 2000-2008 to 13.5 for 2009-2016. Over 2000-2016, there were 64 drug authorisations for haematological, 15 for breast, and 12 for skin cancer, but none for oesophageal, brain, bladder, or uterine cancer. Only 6% of authorisations included a paediatric indication. The average time for a drug to progress from patent priority date to availability on the National Health Service (NHS) increased from 12.8 years for drugs first licensed in 2000-2008 to 14.0 years for those licensed in 2009-2016. There was evidence that the most innovative drugs were not being prioritised for EMA licensing and NICE approval

Validation of Continuous Glucose Monitoring in Children and Adolescents With Cystic Fibrosis: A prospective cohort study

OBJECTIVE: To validate continuous glucose monitoring (CGM) in children and adolescents with cystic fibrosis. RESEARCH DESIGN AND METHODS: Paired oral glucose tolerance tests (OGTTs) and CGM monitoring was undertaken in 102 children and adolescents with cystic fibrosis (age 9.5-19.0 years) at baseline (CGM1) and after 12 months (CGM2). CGM validity was assessed by reliability, reproducibility, and repeatability. RESULTS: CGM was reliable with a Bland-Altman agreement between CGM and OGTT of 0.81 mmol/l (95% CI for bias +/- 2.90 mmol/l) and good correlation between the two (r = 0.74-0.9; P < 0.01). CGM was reproducible with no significant differences in the coefficient of variation of the CGM assessment between visits and repeatable with a mean difference between CGM1 and CGM2 of 0.09 mmol/l (95% CI for difference +/- 0.46 mmol/l) and a discriminant ratio of 13.0 and 15.1, respectively. CONCLUSIONS: In this cohort of children and adolescents with cystic fibrosis, CGM performed on two occasions over a 12-month period was reliable, reproducible, and repeatable

Learning L2 collocations incidentally from reading

Previous studies have shown that intentional learning through explicit instruction is effective for the acquisition of collocations in a second language (L2) (e.g. Peters, 2014, 2015), but relatively little is known about the effectiveness of incidental approaches for the acquisition of L2 collocations. The present study examined the incidental acquisition of collocational knowledge when learners encounter adjective-pseudoword collocations while reading. Forty-one L2 learners read a story containing six target collocations in a classroom setting. One week after the reading they were interviewed about their knowledge of the form, meaning and collocation of the target items (at recall and recognition levels). Participants were randomly assigned to one of two experimental groups, i.e. the 4-repetition group and the 8-repetition group. Results showed that collocational knowledge can be learnt incidentally from reading; that it is learnt at a similar rate to other lexical components such as form and meaning of individual words; and that the frequency manipulation in this study did not seem to have a significant effect on the acquisition of any of the aspects examined

A regional benthic fauna assessment method for the Southern North Sea using Margalef diversity and reference value modelling

The aims of this study are to develop an optimized method for regional benthic fauna assessment of the Southern North Sea which (a) is sensitive and precise (quantified as the slope and the R2 value of the pressure-impact relationships, respectively) for the anthropogenic pressures bottom fishing and organic enrichment, (b) is suitable for estimating and modelling reference values, (c) is transparent, (d) can be efficiently applied using dedicated software; and to apply this method to benthic data from the Southern North Sea. Margalef diversity appeared to be the best performing benthic index regarding these criteria, even better than several Multi-Metric Indices (MMIs) containing e.g. AMBI (AZTI Marine Biotic Index) and ITI (Infaunal Trophic Index). Therefore, this relatively simple and very practical index, including a new reference value estimation and modelling method, and BENMMI software were selected as a common OSPAR (Oslo Paris convention) method for the benthic fauna assessment of the Southern North Sea. This method was applied to benthic fauna data from the Southern North Sea collected during the period 2010–2015. The results in general show lower normalized Margalef values in coastal areas, and higher normalized Margalef values in deeper offshore areas. The following benthic indices were compared in this study: species richness, Margalef diversity, SNA index, Shannon index, PIE index, AMBI, ITI. For each assessment area, the least disturbed benthic dataset was selected as an adjacent 6 year period with, on average, the highest Margalef diversity values. For these datasets, the reference values were primarily set as the 99th percentile values of the respective indices. This procedure results in the highest stable reference values that are not outliers. In addition, a variable percentile method was developed, in which the percentile value is adjusted to the average bottom fishing pressure (according to data from the International Council for the Exploration of the Sea, ICES) in the period 2009–2013. The adjusted percentile values were set by expert judgement, at 75th (low fishing pressure), 95th (medium fishing pressure) and 99th (high fishing pressure) percentile. The estimated reference values for Margalef diversity correlate quite well with the median depth of the assessment areas using a sigmoid model (pseudo-R2 = 0.86). This relationship between depth and Margalef diversity was used to estimate reference values in case an assessment area had insufficient benthic data .For testing the effects of bottom fishing pressure, normalized index values (NIV; index value divided by reference value) were used. The rationale for using NIVs is the assumption that, although a certain level of bottom fishing pressure will have a larger absolute effect on more biodiverse benthic communities in deeper waters than on more robust and less biodiverse coastal benthic communities, the relative effects (tested using NIVs) are comparable. A clear exponentially decreasing relationship (R2 = 0.26–0.27, p 2 cm, respectively) and normalized Margalef diversity values, with an asymptotic normalized Margalef value of 0.45 at a subsurface fishing activity >2.3 sweeps/year. This asymptotic value is predominantly found in coastal waters, and probably shows that the naturally more robust coastal benthic communities have been transformed into resilient benthic communities, which rapidly recover from increasing fishing pressure

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Different bottom trawl fisheries have a differential impact on the status of the North Sea seafloor habitats

Fisheries using bottom trawls are the most widespread source of anthropogenic physical disturbance to seafloor habitats. To mitigate such disturbances, the development of fisheries-, conservation-, and ecosystem-based management strategies requires the assessment of the impact of bottom trawling on the state of benthic biota. We explore a quantitative and mechanistic framework to assess trawling impact. Pressure and impact indicators that provide a continuous pressure–response curve are estimated at a spatial resolution of 1 χ 1 min latitude and longitude (~2 km2) using three methods: L1 estimates the proportion of the community with a life span exceeding the time interval between trawling events; L2 estimates the decrease in median longevity in response to trawling; and population dynamic (PD) estimates the decrease in biomass in response to trawling and the recovery time. Although impact scores are correlated, PD has the best performance over a broad range of trawling intensities. Using the framework in a trawling impact assessment of ten métiers in the North Sea shows that muddy habitats are impacted the most and coarse habitats are impacted the least. Otter trawling for crustaceans has the highest impact, followed by otter trawling for demersal fish and beam trawling for flatfish and flyshooting. Beam trawling for brown shrimps, otter trawling for industrial fish, and dredging for molluscs have the lowest impact. Trawling is highly aggregated in core fishing grounds where the status of the seafloor is low but the catch per unit of effort (CPUE) per unit of impact is high, in contrast to peripheral grounds, where CPUE per unit of impact is low.</p