852 research outputs found
Game Theoretical Interactions of Moving Agents
Game theory has been one of the most successful quantitative concepts to
describe social interactions, their strategical aspects, and outcomes. Among
the payoff matrix quantifying the result of a social interaction, the
interaction conditions have been varied, such as the number of repeated
interactions, the number of interaction partners, the possibility to punish
defective behavior etc. While an extension to spatial interactions has been
considered early on such as in the "game of life", recent studies have focussed
on effects of the structure of social interaction networks.
However, the possibility of individuals to move and, thereby, evade areas
with a high level of defection, and to seek areas with a high level of
cooperation, has not been fully explored so far. This contribution presents a
model combining game theoretical interactions with success-driven motion in
space, and studies the consequences that this may have for the degree of
cooperation and the spatio-temporal dynamics in the population. It is
demonstrated that the combination of game theoretical interactions with motion
gives rise to many self-organized behavioral patterns on an aggregate level,
which can explain a variety of empirically observed social behaviors
GMOs: Non-Health Issues
The controversy over genetically modified [GM] organisms is often framed in terms of possible hazards for human health. Articles in a previous volume of this *Encyclopedia* give a general overview of GM crops [@Mulvaney2014] and specifically examine human health [@Nordgard2014] and labeling [@Bruton2014] issues surrounding GM organisms. This article explores several other aspects of the controversy: environmental concerns, political and legal disputes, and the aim of "feeding the world" and promoting food security. Rather than discussing abstract, hypothetical GM organisms, this article explores the consequences of the GM organisms that have actually been deployed in the particular contexts that they have been deployed, on the belief that there is little point in discussing GM organisms in an idealized or context-independent way
Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions
The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits
Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial
BACKGROUND: Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation. METHODS: BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz. FINDINGS: Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50). CONCLUSIONS: Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring. TRIAL REGISTRATION: EudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016
The Eastern Origins of the Rise of the West and the “Return” of Asia
With the current interest in China (and India) proliferating within the Western Academy, this article claims that what we are witnessing today is not the rise but the “return” of China (and India). Many academics assume that the West has been the dominant civilization in the world economy in the last 500 years and that the current “rise” of China threatens to knock the West off its perch. However, this article provides an alternative take to this cherished axiom of Eurocentric world history by inverting the standard belief that the West pioneered modernity and then expanded outwards to remake the world. Thus, I argue not only that globalization preceded the rise of the West but that it was Eastern-led on the one hand and that it enabled the Western breakthrough into modernity on the other. This, in turn, rests on my claim that Chinese development stems back not to 1978 but to 960 ce as the Sung Dynasty emerged and subsequently undertook a quasi-industrial miracle. Moreover, between 1450/1492 and ca. 1830 China lay at the centre of the nascent global economy, fanning the integration process alongside other key non-Western regions such as India and West Asia/North Africa. And, while the West was the dominant player after ca. 1830 down to the turn of the third millennium, nevertheless, what we witness today is the return of China to the centre of the global economy whence it came
Divergent mind-sets, convergent policies: Policing models against organized crime in Italy and in England within international frameworks
The fight against organized crime is a very fertile ground for policymaking at various levels. On one side, because of the perceived transnationality of the phenomenon, national states are inclined to develop harmonized responses within the European or international law frameworks. On the other side, national conceptualizations and manifestations of organized crime often make these harmonizations quite challenging. This paper shares the findings of a socio-legal investigation carried out in England and in Italy through interviews and document analysis, comparing the two national models against organized crime. The paper presents these two models ? the Italian Structure Model and the English Activity Model, which are very different in many ways ? in order to identify divergences and convergences of policies and practices. This comparative exercise not only improves our understanding of national approaches, beyond cultural, linguistic and legal boundaries, but also improves the dialogue towards concerted efforts at the international level. Nevertheless, the globalization of criminal markets and the internationalization of policies have influenced perceptions of organized crime and related policing tactics at national levels too. This paper will briefly look at international perspectives to assess to what extent divergent and convergent areas between the two models are also areas of interest and focus at the international level, in order to conclude with an enhanced understanding of both models before drawing conclusions
The role of power in financial statement fraud schemes
In this paper, we investigate a large-scale financial statement fraud to better understand the process by which individuals are recruited to participate in financial statement fraud schemes. The case reveals that perpetrators often use power to recruit others to participate in fraudulent acts. To illustrate how power is used, we propose a model, based upon the classical French and Raven taxonomy of power, that explains how one individual influences another individual to participate in financial statement fraud. We also provide propositions for future research
Environmental harm and environmental victims: scoping out a ‘green victimology'
In this paper I intend to discuss the adaptability of victimological study to the question of ‘environmental victimisation’. The impact on those affected by environment crime, or other environmentally damaging activities, is one that has received scarce attention in the mainstream victimological literature (see Williams, 1996). The role or position of such victims in criminal justice and/or other processes has likewise rarely been topic of academic debate. I have recently expanded upon various aspects of this subject and surrounding issues at greater length (Hall, 2013) but for the purposes of this article I wish to expand specifically on what a so-called ‘green victimology’ might look like, together with some of the particular questions and challenges it will face
Bi-modal confirmation of liposome delivery to the brain after focused ultrasound-induced blood-brain barrier opening
Focused ultrasound-mediated opening of the blood-brain barrier offers a great opportunity to deliver therapeutics into hard-to-treat brain tumors such as glioblastoma multiforme or diffuse midline glioma. However, the potential of the technique to offer a time window for efficient nanomedicine delivery has not been thoroughly studied. Non-invasive and targeted delivery of large drug-loaded nanocarriers, such as liposomes, could offer a safe and scalable method of personalized therapy for the treatment of brain pathologies. Additionally, it is essential to monitor the safety and efficacy of such treatments, tracking drug delivery in real-time through quantitative medical imaging. In this study, liposomes were modified to have an MRI contrast agent (i.e., Gd) in both lipid membrane and core, while an infrared dye (i.e., CW800) was coupled to lipids introduced in the lipid bilayer for bimodal detection and treatment verification. Targeted delivery of 110 nm-in-diameter liposomes to the brain was quantified using 9.4-T MRI and near infrared fluorescence imaging. The spatiotemporal distribution of liposomes in vivo was assessed up to 4 h post treatment using T1 weighted MRI. In vivo MRI signal co-localized with NIRF signal from excised brains ex vivo. Passive acoustic detection during treatments revealed a correlation between acoustic signal and MRI contrast, providing a scalable metric for assessing clinical treatment efficacy in real-time. In conclusion, therapeutic ultrasound exposure can enhance delivery of large trackable nanoparticles into the brain, while enabling real-time treatment monitoring and verification
Brief Report: Dolutegravir Plasma Protein Binding and Unbound Concentrations During Pregnancy and Postpartum
BackgroundClinical interpretation of the reduced dolutegravir (DTG) plasma concentrations reported during pregnancy is complicated by its high plasma protein binding. Plasma proteins significantly decrease during pregnancy, and understanding changes in DTG protein binding and its therapeutically active unbound concentrations are necessary to evaluate the impact of pregnancy changes on DTG pharmacokinetics.MethodsRetrospective assessment of plasma samples from pregnant women living with HIV enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s study receiving 50 mg DTG film-coated tablets once daily as part of clinical care. Unbound and total DTG concentrations were determined predose (C0) and at maximum (Cmax) concentrations during the second trimester (2T), third trimester (3T), and postpartum (PP). Percentage unbound was calculated as the ratio of ultrafiltrate unbound DTG concentration to total DTG concentration.ResultsTwenty-nine mothers were included for protein binding evaluations; 15, 27, and 23 from the 2T, 3T, and PP, respectively. DTG % unbound for C0 and Cmax were significantly different by stage of pregnancy, with 3T significantly higher compared with PP; 1.02% vs. 0.69% (P = 0.0067) for C0 and 0.76% vs. 0.46% for Cmax (P = 0.0056). Median (IQR) unbound concentrations for C0 were 6.3 (4.7-18.4) for the 2T, 8.0 (5.6-16.9) for the 3T, and 13.3 (8.4-22.7) ng/mL PP, significantly different between 2T and PP (P = 0.0039), but not different between 3T and PP (P = 0.46).ConclusionLower total DTG plasma concentrations during pregnancy coincide with temporal decreases in DTG protein binding, resulting in comparable unbound DTG concentrations during the 3T and PP
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