Multi-train trajectory optimisation to maximise rail network energy efficiency under travel-time constraints

Optimising the trajectories of multiple interacting trains to maximise energy efficiency is a difficult, but highly desirable, problem to solve. A bespoke genetic algorithm has been developed for the multi-train trajectory optimisation problem and used to seek a near-optimal set of control point distances for multiple trains, such that a weighted sum of the time and energy objectives is minimised. Genetic operators tailored to the problem are developed including a new mutation operation and the insertion and deletion pairs of control points during the reproduction process. Compared with published results, the new GA was shown to increase the quality of solutions found by an average of 27.6% and increase consistency by a factor of 28. This allows more precise control over the relative priority given to achieving time targets or increasing energy efficiency

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

Using high-resolution LiDAR data to quantify the three-dimensional structure of vegetation in urban green space

The spatial arrangement and vertical structure of vegetation in urban green spaces are key factors in determining the types of benefits that urban parks provide to people. This includes opportunities for recreation, spiritual fulfilment and biodiversity conservation. However, there has been little consideration of how the fine-scale spatial and vertical structure of vegetation is distributed in urban parks, primarily due to limitations in methods for doing so. We addressed this gap by developing a method using Light Detection and Ranging (LiDAR) data to map, at a fine resolution, tree cover, vegetation spatial arrangement, and vegetation vertical structure. We then applied this method to urban parks in Brisbane, Australia. We found that parks varied mainly in their amount of tree cover and its spatial arrangement, but also in vegetation vertical structure. Interestingly, the vertical structure of vegetation was largely independent of its cover and spatial arrangement. This suggests that vertical structure may be being managed independently to tree cover to provide different benefits across urban parks with different levels of tree cover. Finally, we were able to classify parks into three distinct classes that explicitly account for both the spatial and vertical structure of tree cover. Our approach for mapping the three-dimensional vegetation structure of urban green space provides a much more nuanced and functional description of urban parks than has previously been possible. Future research is now needed to quantify the relationships between vegetation structure and the actual benefits people derive from urban green space.</p