Optimal Investment in the Development of Oil and Gas Field

Let an oil and gas field consists of clusters in each of which an investor can launch at most one project. During the implementation of a particular project, all characteristics are known, including annual production volumes, necessary investment volumes, and profit. The total amount of investments that the investor spends on developing the field during the entire planning period we know. It is required to determine which projects to implement in each cluster so that, within the total amount of investments, the profit for the entire planning period is maximum. The problem under consideration is NP-hard. However, it is solved by dynamic programming with pseudopolynomial time complexity. Nevertheless, in practice, there are additional constraints that do not allow solving the problem with acceptable accuracy at a reasonable time. Such restrictions, in particular, are annual production volumes. In this paper, we considered only the upper constraints that are dictated by the pipeline capacity. For the investment optimization problem with such additional restrictions, we obtain qualitative results, propose an approximate algorithm, and investigate its properties. Based on the results of a numerical experiment, we conclude that the developed algorithm builds a solution close (in terms of the objective function) to the optimal one

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration

AIMS: To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events. METHODS AND RESULTS: Using two case–control studies, three cross-sectional, and seven prospective studies with up to 25 000 individuals and 5794 CHD events we evaluated associations of 34 genome-wide-association study-identified SNPs with CHD risk and 16 CHD-associated risk factors or biomarkers. The Ch9p21 SNPs rs1333049 (OR 1.17; 95% confidence limits 1.11–1.24) and rs10757274 (OR 1.17; 1.09–1.26), MIA3 rs17465637 (OR 1.10; 1.04–1.15), Ch2q36 rs2943634 (OR 1.08; 1.03–1.14), APC rs383830 (OR 1.10; 1.02, 1.18), MTHFD1L rs6922269 (OR 1.10; 1.03, 1.16), CXCL12 rs501120 (OR 1.12; 1.04, 1.20), and SMAD3 rs17228212 (OR 1.11; 1.05, 1.17) were all associated with CHD risk, but not with the CHD biomarkers and risk factors measured. Among the 20 blood lipid-related SNPs, LPL rs17411031 was associated with a lower risk of CHD (OR 0.91; 0.84–0.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.15–1.26) as well as total- and LDL-cholesterol, and apolipoprotein B. ANGPTL3 rs12042319 was associated with CHD risk (OR 1.11; 1.03, 1.19), total- and LDL-cholesterol, triglycerides, and interleukin-6. CONCLUSION: Several SNPs predicting CHD events appear to involve pathways not currently indexed by the established or emerging risk factors; others involved changes in blood lipids including triglycerides or HDL-cholesterol as well as LDL-cholesterol. The overlapping association of SNPs with multiple risk factors and biomarkers supports the existence of shared points of regulation for these phenotypes

Dental calculus evidence of Taï Forest Chimpanzee plant consumption and life history transitions

Dental calculus (calcified dental plaque) is a source of multiple types of data on life history. Recent research has targeted the plant microremains preserved in this mineralised deposit as a source of dietary and health information for recent and past populations. However, it is unclear to what extent we can interpret behaviour from microremains. Few studies to date have directly compared the microremain record from dental calculus to dietary records, and none with long-term observation dietary records, thus limiting how we can interpret diet, food acquisition and behaviour. Here we present a high-resolution analysis of calculus microremains from wild chimpanzees (Pan troglodytes verus) of Taï National Park, Côte d"Ivoire. We test microremain assemblages against more tan two decades of field behavioural observations to establish the ability of calculus to capture the composition of diet. Our results show that some microremain classes accumulate as long-lived dietary markers. Phytolith abundance in calculus can reflect the proportions of plants in the diet, yet this pattern is not true for starches. We also report microremains can record information about other dietary behaviours, such as the age of weaning and learned food processing techniques like nutcracking

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland:Scottish Family Health Study (GS:SFHS)

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average πN = 0.0033 and average πS = 0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease

An Anatomy Massive Open Online Course as a Continuing Professional Development Tool for Healthcare Professionals

Massive open online courses (MOOCs) remain a novel and under-evaluated learning tool within anatomical and medical education. This study aimed to provide valuable information by using an anatomy MOOC to investigate the demographic profile, patterns of engagement and self-perceived benefits to healthcare professionals. A 21-item survey aimed at healthcare professionals was embedded into the Exploring Anatomy: The Human Abdomen MOOC, in April 2016. The course attracted 2711 individual learners with 94 of these completing the survey, and 79 of those confirming they worked full- or part-time as healthcare professionals. Variations in use across healthcare profession (allied healthcare professional, nurse or doctor) were explored using a Fisher’s exact test to calculate significance across demographic, motivation and engagement items; one-way ANOVA was used to compare self-perceived benefits. Survey data revealed that 53.2% were allied healthcare professionals, 35.4% nurses and 11.4% doctors. Across all professions, the main motivation for enrolling was to learn new things in relation to their clinical practice, with a majority following the prescribed course pathway and utilising core, and clinically relevant, material. The main benefits were in relation to improving anatomy knowledge, which enabled better support for patients. This exploratory study assessing engagement and self-perceived benefits of an anatomy MOOC has shown a high level of ordered involvement, with some indicators suggesting possible benefits to patients by enhancing the subject knowledge of those enrolled. It is suggested that this type of learning tool should be further explored as an approach to continuing professional, and interprofessional, education

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201

Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial

Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. National Institute of Health and Research Health Technology Assessment. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.