The Cost of Compositionality: A High-Performance Implementation of String Diagram Composition

String diagrams are an increasingly popular algebraic language for the analysis of graphical models of computations across different research fields. Whereas string diagrams have been thoroughly studied as semantic structures, much fewer attention has been given to their algorithmic properties, and efficient implementations of diagrammatic reasoning are almost an unexplored subject. This work intends to be a contribution in such direction. We introduce a data structure representing string diagrams in terms of adjacency matrices. This encoding has the key advantage of providing simple and efficient algorithms for composition and tensor product of diagrams. We demonstrate its effectiveness by showing that the complexity of the two operations is linear in the size of string diagrams. Also, as our approach is based on basic linear algebraic operations, we can take advantage of heavily optimised implementations, which we use to measure performances of string diagrammatic operations via several benchmarks

Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal

Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings. Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury. Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement. Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p

Optimality-based Analysis of XCSF Compaction in Discrete Reinforcement Learning

Learning classifier systems (LCSs) are population-based predictive systems that were originally envisioned as agents to act in reinforcement learning (RL) environments. These systems can suffer from population bloat and so are amenable to compaction techniques that try to strike a balance between population size and performance. A well-studied LCS architecture is XCSF, which in the RL setting acts as a Q-function approximator. We apply XCSF to a deterministic and stochastic variant of the FrozenLake8x8 environment from OpenAI Gym, with its performance compared in terms of function approximation error and policy accuracy to the optimal Q-functions and policies produced by solving the environments via dynamic programming. We then introduce a novel compaction algorithm (Greedy Niche Mass Compaction - GNMC) and study its operation on XCSF's trained populations. Results show that given a suitable parametrisation, GNMC preserves or even slightly improves function approximation error while yielding a significant reduction in population size. Reasonable preservation of policy accuracy also occurs, and we link this metric to the commonly used steps-to-goal metric in maze-like environments, illustrating how the metrics are complementary rather than competitive

The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic-industrial partnership

Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections

Ceramides: a new player in the inflammation-insulin resistance paradigm?

No abstract available

Health status in COPD cannot be measured by the St George's Respiratory Questionnaire alone: an evaluation of the underlying concepts of this questionnaire

Contains fulltext : 88421.pdf (publisher's version ) (Open Access)BACKGROUND: Improving patients' health status is one of the major goals in COPD treatment. Questionnaires could facilitate the guidance of patient-tailored disease management by exploring which aspects of health status are problematic, and which aspects are not. Health status consists of four main domains (physiological functioning, symptoms, functional impairment, and quality of life), and at least sixteen sub-domains. A prerequisite for patient-tailored treatment is a detailed assessment of all these sub-domains. Most questionnaires developed to measure health status consist of one or a few subscales and measure merely some aspects of health status. The question then rises which aspects of health status are measured by these instruments, and which aspects are not covered. As it is one of the most frequently used questionnaires in COPD, we evaluated which aspects of health status are measured and which aspects are not measured by the St George's Respiratory Questionnaire (SGRQ). METHODS: One hundred and forty-six outpatients with COPD participated. Correlations were calculated between the three sections of the SGRQ and ten sub-domains of the Nijmegen Integral Assessment Framework, covering Symptoms, Functional Impairment, and Quality of Life. As the SGRQ was not expected to measure physiological functioning, we did not include this main domain in the statistical analyses. Pearson's r > or = 0.70 was used as criterion for conceptual similarity. RESULTS: The SGRQ sections Symptoms and Total showed conceptual similarity with the sub-domain Subjective Symptoms (main domain Symptoms). The sections Activity, Impacts and Total were conceptual similar to Subjective Impairment (main domain Functional Impairment). The SGRQ sections were not conceptual similar to other sub-domains of Symptoms, Functional Impairment, nor to any sub-domain of Quality of Life. CONCLUSIONS: The SGRQ could facilitate the guidance of disease management in COPD only partially. The SGRQ is appropriately only for measuring problems in the sub-domains Subjective Symptoms and Subjective Impairment, and not for measuring problems in other sub-domains of health status, such as Quality of Life

A comparison of local phosphorescence detection and fluid dynamic gauging methods for studying the removal of cohesive fouling layers: Effect of layer roughness

The performance of industrial cleaning in place (CIP) procedures is critically important for food manufacture. CIP has yet to be optimised for many processes, in part since the mechanisms involved in cleaning are not fully understood. Laboratory tests have an important role in guiding industrial trials, and this paper introduces and compares two experimental techniques developed for studying CIP mechanisms: local phosphorescence detection (LPD), and scanning fluid dynamic gauging (sFDG). To illustrate the comparison, each technique is used to investigate the influence of soil topology on the cleaning of pre-gelatinised starch-based layers from 316 stainless steel substrates by aqueous NaOH solutions at ambient temperature. The roughness of the soil surface is varied by incorporating zinc sulphide particles with different particle size distributions (range 1 - 80 μm) into the starch suspensions. The soil roughness increased with the use of larger particles, increasing the 3D arithmetic mean roughness (Sa) of the dry layers (range 0.37 - 3.33 μm). Rough layers were cleaned more readily than those containing small inclusions, with a good correlation between the cleaning rates observed during LPD and FDG measurements. The LPD technique, which is an instrumented CIP test, gives a better indication of the cleaning time, while sFDG measurements provide further insight into the removal mechanisms.NOTICE: this is the author's version of a work that was accepted for publication in Food Bioproducts Processing. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Food Bioproducts Proc., 92, 46-53 DOI http://dx.doi.org/10.1016/j.fbp.2013.07.01

Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Background: Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.Methods: 308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded. From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index. The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts.Results: All four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters. The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively. Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham. The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death.Conclusions: This study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions. The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems

Baseline Severity as Predictor of Change in St George's Respiratory Questionnaire Scores in Trials of Long-acting Bronchodilators with COPD Patients.

Background: In trials oflong-acting bronchodilators, health status is an important trial outcome, however the influence of baseline severity on response measured by St George's Respiratory Questionnaire (SGRQ) is not known. We have compared SGRQ changes between patients with chronic obstructive pulmonary disease (COPD) of mild-moderate severity or dyspnea (Global initiative for chronic Obstructive Lung disease [GOLD] grades 1 and 2; modified Medical Research Council [mMRC] grades 1 and 2) to those with severe-very severe severity or dyspnea (GOLD grades 3 and 4; mMRC grades 3 and 4). Methods: Combined individual patient data from the COPD Biomarkers Qualification Consortium database (trials of long-acting bronchodilators) were used comprising of patients from short-term (≤1-year duration; n=10802) and medium-term (2-4 years' duration; n=8963) studies. A repeated measures analysis of variance (ANOVA) was used to determine the effects of baseline severity (GOLD/mMRC) on SGRQ response to treatment. All treatment arms were combined. Results: In short-term studies, milder patients showed a greater response than those with more severe disease in terms of GOLD grade (partial Eta(2) = 0.03, p < 0.0001) and mMRC grade (partial Eta(2) = 0.05, p < 0.0001). Similar results were seen in the medium-term studies (partial Eta(2) = 0.02, p < 0.0001; mMRC: partial Eta(2) = 0.05, p < 0.0001,). Conclusions: Patients with less severe airflow limitation and less severe dyspnea showed larger improvements in SGRQ score than more severely obstructed or dyspneic patients. Although these severity influences are small (2%-5% of the variance in SGRQ score), they do suggest that pre-specified separate analyses are warranted to test for differences in response, based on baseline severity

Responder Analyses for Treatment Effects in COPD Using the St George's Respiratory Questionnaire.

Background: Patient-reported outcomes data in clinical trials are usually reported as mean values, interpreted in comparison to a minimum clinically important difference (MCID) and ignoring the possibility of a sizable proportion of patients experiencing a worthwhile benefit when the majority did not. This analysis tested the reliability of calculated responder rates (from chronic obstructive pulmonary disease [COPD] patients) with the St George's Respiratory Questionnaire (SGRQ) using a range of responder cut-points above and below the MCID (4 units). Methods: Individual patient data (i.e., data from long-acting bronchodilator [LAB] and inhaled corticosteroids [ICS]/long-acting beta2-agonist [LABA] randomized clinical studies) in the COPD Biomarker Qualification Consortium database were used: short-term (≤1-year duration; 14,814 patients,) and medium-term (2-4 years; 12,043 patients). Responder rates versus placebo across SGRQ score change thresholds ranging from -1.5 to -8.0 were tested; differences were expressed as the odds ratio (OR) of a patient exceeding the threshold versus no change or deterioration. Results: The ORs measuring benefit of active treatment were similar across thresholds in short-term studies (LAB, ORs 1.40-1.42; LABA/ICS, 1.50-1.56) and medium-term LAB studies (ORs 1.34-1.43), whereas ORs in medium-term studies with LABA/ICS intervention showed a trend for higher response rates at higher values of threshold cut-points (1.64-1.79). In short-term studies, different thresholds had little effect on the OR between active drugs versus a trend for lower ORs with lower thresholds in medium-term studies. Conclusions: The OR for a treatment effect compared with placebo appears consistent across a range of responder cut-points. In medium-term trials, the treatment difference between active drugs suggests that use of a lower threshold would not increase the odds of observing a measured treatment difference