161 research outputs found

    Crime in Game Theoretic Models: An exploration of the rational criminal in a variety of frameworks

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    There is as much contention over the cause of crime as there is about how to solve it, and the two issues are inextricable from one another. While the idea of studying such a deeply social and humanistic issue through the ‘cold lens’ of mathematics may seem unorthodox or even unproductive to the layperson, the practice has become commonplace since Gary Becker’s introduction of the ‘rational criminal’ model in his paper Crime and Punishment: An Economic Approach in 1968. The rational criminal model is a method of explaining the actions of a criminal not by attributing them to an inherent mental difference or deficiency, nor by some product of social repression, but as decisions to be calculated in the same manner as all economic choices: a rational consideration of the costs and benefits of committing such an action. That this seems a natural way of looking at crime in the present day is a testament to its effectiveness in understanding some aspects of crime, as it was by no means orthodox when it was first proposed; the dominant view prior to Becker’s contribution was that criminals were produced by a combination of mental deficiency/illness and social oppression. Since this model entered the mainstream, the field of economics has subsumed many areas of crime research, and indeed a variety of other societal phenomena which would have previously been claimed by sociology or psychology. This paper will focus on the prevention aspect: What methods are most effective in preventing or reducing crime, and what approaches have we yet to study? The methodology of the paper is as follows: First, a simple game is introduced in which rational actors use Bayesian Inference to decide whether or not to commit a crime. This game is then modified by adding a false arrest component. Secondly, a simulation of a pure coordination game is constructed, in order to determine the effectiveness of an unrelated choreographer at producing and maintaining certain equilibria

    On-board processing satellite network architecture and control study

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    The market for telecommunications services needs to be segmented into user classes having similar transmission requirements and hence similar network architectures. Use of the following transmission architecture was considered: satellite switched TDMA; TDMA up, TDM down; scanning (hopping) beam TDMA; FDMA up, TDM down; satellite switched MF/TDMA; and switching Hub earth stations with double hop transmission. A candidate network architecture will be selected that: comprises multiple access subnetworks optimized for each user; interconnects the subnetworks by means of a baseband processor; and optimizes the marriage of interconnection and access techniques. An overall network control architecture will be provided that will serve the needs of the baseband and satellite switched RF interconnected subnetworks. The results of the studies shall be used to identify elements of network architecture and control that require the greatest degree of technology development to realize an operational system. This will be specified in terms of: requirements of the enabling technology; difference from the current available technology; and estimate of the development requirements needed to achieve an operational system. The results obtained for each of these tasks are presented

    Investigations into cubane based analogues of current pharmaceuticals

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    The cubane core has been shown to be physically similar to benzene across the body diagonal, yet remains electronically and physically different in all other ways. It is proposed that this similarity may allow cubane to act as a bioisostere for benzene in pharmaceutical applications. As such, a number of novel synthetic approaches have been used to develop new routes to previously unknown cubane derivatives. The synthesis of several novel cubane based compounds is described herein. The synthetic routes contained within provide further insight into the potential functional group modifications for the cubane framework. These derivatives form key intermediates in the synthesis of a number of target analogues based in a variety of drug classes. These classes include anticancer chemotherapeutic drugs, novel Alzheimer’s disease compounds, antibacterial compounds, topical scabies medications as well as a well known antifungal compound. The overall study is designed to act as a base level investigation into the potential of cubane to act as a bioisostere for benzene in pharmaceutical analogues. Compounds were selected based upon the presence of a benzene ring, drug class as well as potential synthetic approach. The described compounds are thus designed to be analogous to current pharmaceutical drugs which are undergoing Phase I clinical trials, later testing, or are already available for purchase. Biological tests of these novel compounds have been subjected to, at least, base level comparison to the known drug analogue. Results of these studies have demonstrated that cubane analogues have similar biological activity to a number of benzene analogues in a variety of classes and thus merit further investigation into the use of cubane as a bioisostere for benzene. Further to this a P450 oxidation study has also been performed to help understand the metabolic processes that may be imparted upon the cubane core in a biological system. The results herein also demonstrate that cubane derived compounds hold great potential for their application in pharmaceutical compounds, yet underline the fact that cubane remains a diamond in the rough, for which many syntheses remain undiscovered

    Synthesis of N-[(dialkylamino)methyl)]acrylamides and N-[(dialkylamino)methyl]methacrylamides from Schiff base salts : useful building blocks for smart polymers

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    The traditional thermal Mannich reaction is unsuitable for preparing polymerizable N-methylene amino substituted acrylamides and methacrylamides. Herein we provide a facile multi-gram high yield synthesis of these monomeric precursors to stimuli-responsive polymers by addition of acrylamide and methacrylamide onto in situ generated or freshly isolated methylene Schiff base (iminium) salts. X-ray crystal structure of the hydrated iminium salt, 1-(hydroxymethyl)azocan-1-ium chloride and monomer.HCl salt, (N-[(azocan-1-yl)methyl]prop-2-enamide hydrochloride) is described

    Genetic and pharmacological relationship between P-Glycoprotein and increased cardiovascular risk associated with clarithromycin prescription:An Epidemiological and Genomic Population-Based Cohort Study in Scotland, UK

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    BackgroundThere are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug-drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism.Methods and findingsWe conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 -AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0-14 days, 15-30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0-14 days (HR 1.31; 95% CI 1.17-1.46, p ConclusionsIn this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein

    Rare musculoskeletal diseases in adults: a research priority setting partnership with the James Lind Alliance

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    Background Osteogenesis imperfecta, fibrous dysplasia/McCune-Albright syndrome and X-linked hypophosphatemia are three rare musculoskeletal diseases characterised by bone deformities, frequent fractures and pain. Little high-quality research exists on appropriate treatment and long-term management of these conditions in adults. This is further worsened by limited research funding in rare diseases and a general mismatch between the existing research priorities and those of the patients. This partnership adopted the James Lind Alliance approach to identify the top 10 research priorities for rare musculoskeletal diseases in adults through joint patient, carer and healthcare professional collaboration. Results The initial survey for question collection recruited 198 respondents, submitting a total of 988 questions. 77% of the respondents were patients with a rare musculoskeletal disease. Following out-of-scope question exclusion, repeating query grouping and scientific literature check for answers, 39 questions on treatment and long-term management remained. In the second public survey, 220 respondents, of whom 85% were patients with a rare musculoskeletal disease, their carers, relatives or friends, prioritised these uncertainties, which allowed selection of the top 25. In the last stage, patients, carers and healthcare professionals gathered for a priority setting workshop to reach a consensus on the final top 10 research priorities. These focus on the uncertainties surrounding appropriate treatment and holistic long-term disease management, highlighting several aspects indirect to abnormal bone metabolism, such as extra-skeletal symptoms, psychological care of both patients and their families and disease course through ageing. Conclusions This James Lind Alliance priority setting partnership is the first to investigate rare bone diseases. The priorities identified here were developed jointly by patients, carers and healthcare professionals. We encourage researchers, funding bodies and other stakeholders to use these priorities in guiding future research for those affected by rare musculoskeletal disorders

    Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection

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    Background Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery. Methods Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020). Patients were enrolled within 96 h of admission, with longitudinal sampling up to 29 days. Control groups comprised non-COVID-19 acute lower respiratory tract infection (LRTI) and age-matched noninfected controls. Neutrophils were isolated from peripheral blood and analysed using mass spectrometry. COVID-19 severity and recovery were defined using the World Health Organization ordinal scale. Results Neutrophil proteomes from 84 COVID-19 patients were compared to those from 91 LRTI and 42 control participants. 5800 neutrophil proteins were identified, with &gt;1700 proteins significantly changed in neutrophils from COVID-19 patients compared to noninfected controls. Neutrophils from COVID-19 patients initially all demonstrated a strong interferon signature, but this signature rapidly declined in patients with severe disease. Severe disease was associated with increased abundance of proteins involved in metabolism, immunosuppression and pattern recognition, while delayed recovery from COVID-19 was associated with decreased granule components and reduced abundance of metabolic proteins, chemokine and leukotriene receptors, integrins and inhibitory receptors. Conclusions SARS-CoV-2 infection results in the sustained presence of circulating neutrophils with distinct proteomes suggesting altered metabolic and immunosuppressive profiles and altered capacities to respond to migratory signals and cues from other immune cells, pathogens or cytokines.</p
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