246 research outputs found

    "The Law is just words after all": Torture, Truth, and Language in the Post-9/11 United States and Percival Everett's The Water Cure

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    Through a reading of Percival Everett's experimental novel, The Water Cure, this essay argues for the need to interrogate the law as literature and language if we are to understand the moral permissibility of torture in the changed cultural and political understandings of war since 9/11. Working from the premise that the law and literature, through language and narrative, create social worlds and are worldmaking, this essay analyzes what happens to the law and narrative when the law writes torture into being. When confronted with the practice of torture, the novel ceases to be worldmaking and instead enacts the world unmade

    An Overview of Current Practice in External Beam Radiation Oncology with Consideration to Potential Benefits and Challenges for Nanotechnology

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    Over the past two decades, there has been a significant evolution in the technologies and techniques employed within the radiation oncology environment. Over the same period, extensive research into the use of nanotechnology in medicine has highlighted a range of potential benefits to its incorporation into clinical radiation oncology. This short communication describes key tools and techniques that have recently been introduced into specific stages of a patient’s radiotherapy pathway, including diagnosis, external beam treatment and subsequent follow-up. At each pathway stage, consideration is given towards how nanotechnology may be combined with clinical developments to further enhance their benefit, with some potential opportunities for future research also highlighted. Prospective challenges that may influence the introduction of nanotechnology into clinical radiotherapy are also discussed, indicating the need for close collaboration between academic and clinical staff to realise the full clinical benefit of this exciting technology

    Biological consequences of nanoscale energy deposition near irradiated heavy atom nanoparticles

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    Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radiotherapy, seeking to take advantage of the increased X-ray absorption of gold compared to soft tissue. However, there is a great discrepancy between physically predicted increases in X-ray energy deposition and experimentally observed increases in cell killing. In this work, we present the first calculations which take into account the structure of energy deposition in the nanoscale vicinity of GNPs and relate this to biological outcomes, and show for the first time good agreement with experimentally observed cell killing by the combination of X-rays and GNPs. These results are not only relevant to radiotherapy, but also have implications for applications of heavy atom nanoparticles in biological settings or where human exposure is possible because the localised energy deposition high-lighted by these results may cause complex DNA damage, leading to mutation and carcinogenesis.</p

    Shaping electron wave functions in a carbon nanotube with a parallel magnetic field

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    A magnetic field, through its vector potential, usually causes measurable changes in the electron wave function only in the direction transverse to the field. Here we demonstrate experimentally and theoretically that in carbon nanotube quantum dots, combining cylindrical topology and bipartite hexagonal lattice, a magnetic field along the nanotube axis impacts also the longitudinal profile of the electronic states. With the high (up to 17T) magnetic fields in our experiment the wave functions can be tuned all the way from "half-wave resonator" shape, with nodes at both ends, to "quarter-wave resonator" shape, with an antinode at one end. This in turn causes a distinct dependence of the conductance on the magnetic field. Our results demonstrate a new strategy for the control of wave functions using magnetic fields in quantum systems with nontrivial lattice and topology.Comment: 5 figure

    Interferon- -Oligodendrocyte Interactions in the Regulation of Experimental Autoimmune Encephalomyelitis

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    Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human demyelinating disorder multiple sclerosis (MS). The immune cytokine interferon-gamma (IFN-gamma) is believed to participate in disease pathogenesis in both EAE and MS. In the present study, we examined the significance of IFN-gamma-oligodendrocyte interactions in the course of EAE. For the purpose of our study, we used the previously described [proteolipid protein/suppressor of cytokine signaling 1 (PLP/SOCS1)] transgenic mouse line that displays suppressed oligodendrocyte responsiveness to IFN-gamma. PLP/SOCS1 mice developed EAE with an accelerated onset associated with enhanced early inflammation and markedly increased oligodendrocyte apoptosis. Moreover, we found that IFN-gamma pretreatment of mature oligodendrocytes in vitro had a protective effect against oxidative stress and the inhibition of proteasome activity and resulted in upregulation in expression of a number of chemokines, including CXCL10 (IP10), CCL2 (MCP-1), CCL3 (MCP-1alpha), and CCL5 (RANTES). These results suggest that IFN-gamma-oligodendrocyte interactions are of significance to the clinical and pathological aspects of EAE. In addition, the present study suggests that oligodendrocytes are not simply targets of inflammatory injury but active participants of the neuroimmune network operating during the course of EAE

    Evaluation of a national complex oral health improvement programme: a population data linkage cohort study in Scotland

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    Objectives Child dental caries is a global public health challenge with high prevalence and wide inequalities. A complex public health programme (Childsmile) was established. We aimed to evaluate the reach of the programme and its impact on child oral health. Setting Education, health and community settings, Scotland-wide. Interventions Childsmile (national oral health improvement programme) interventions: nursery-based fluoride varnish applications (FVAs) and supervised daily toothbrushing, community-based Dental Health Support Worker (DHSW) contacts and primary care dental practice visits—delivered to the population via a proportionate universal approach. Participants: 50 379 children (mean age=5.5 years, SD=0.3) attending local authority schools (2014/2015). Design: Population-based individual child-level data on four Childsmile interventions linked to dental inspection survey data to form a longitudinal cohort. Logistic regression assessed intervention reach and the independent impact of each intervention on caries experience, adjusting for age, sex and area-based Scottish Index of Multiple Deprivation (SIMD). Outcome measures: Reach of the programme is defined as the percentage of children receiving each intervention at least once by SIMD fifth. Obvious dental caries experience (presence/absence) is defined as the presence of decay (into dentine), missing (extracted) due to decay or filled deciduous teeth. Results: 15 032 (29.8%) children had caries experience. The universal interventions had high population reach: nursery toothbrushing (89.1%), dental practice visits (70.5%). The targeted interventions strongly favoured children from the most deprived areas: DHSW contacts (SIMD 1: 29.5% vs SIMD 5: 7.7%), nursery FVAs (SIMD 1: 75.2% vs SIMD 5: 23.2%). Odds of caries experience were markedly lower among children participating in nursery toothbrushing (&gt;3 years, adjusted OR (aOR)=0.60; 95% CI 0.55 to 0.66) and attending dental practice (≥6 visits, aOR=0.55; 95% CI 0.50 to 0.61). The findings were less clear for DHSW contacts. Nursery FVAs were not independently associated with caries experience. Conclusions: The universal interventions, nursery toothbrushing and regular dental practice visits were independently and most strongly associated with reduced odds of caries experience in the cohort, with nursery toothbrushing having the greatest impact among children in areas of high deprivation

    Public Health and the Built Environment: Historical, Empirical, and Theoretical Foundations for an Expanded Role

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    In 2000, the Center for Disease Control and Prevention\u27s National Center for Environmental Health issued a report that explored some of the ways in which sprawl impacts public health. The report has generated great interest, and state health officials are beginning to discuss the relationship between land use and public health. The CDC report has also produced a backlash. For example, the Southern California Building Industry Association labeled the report a ludicrous sham and argued that the CDC should stick to fighting physical diseases, not defending political ones. In this environment, it is understandable if the CDC looks to such critiques as simply the latest partisan recruit to a political debate. But critics of the CDC\u27s efforts in this area may substantially overstate their case in the other direction. There is now and has long been a demonstrated connection between health, including physical disease, and the built environment. Moreover, government has intervened in the past in response to this connection and it continues to do so. While neither past practice nor current evidence make government intervention inevitable, this paper argues that such intervention is appropriate and supported by theory as well as history and empirical evidence

    What are the main inefficiencies in trial conduct : a survey of UKCRC registered clinical trials units in the UK

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    BACKGROUND: The UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Units (CTUs) Network aims to support high-quality, efficient and sustainable clinical trials research in the UK. To better understand the challenges in efficient trial conduct, and to help prioritise tackling these challenges, we surveyed CTU staff. The aim was to identify important inefficiencies during two key stages of the trial conduct life cycle: (i) from grant award to first participant, (ii) from first participant to reporting of final results. METHODS: Respondents were asked to list their top three inefficiencies from grant award to recruitment of the first participant, and from recruitment of the first participant to publication of results. Free text space allowed respondents to explain why they thought these were important. The survey was constructed using SurveyMonkey and circulated to the 45 registered CTUs in May 2013. Respondents were asked to name their unit and job title, but were otherwise anonymous. Free-text responses were coded into broad categories. RESULTS: There were 43 respondents from 25 CTUs. The top inefficiency between grant award and recruitment of first participant was reported as obtaining research and development (R&D) approvals by 23 respondents (53%), contracts by 22 (51%), and other approvals by 13 (30%). The top inefficiency from recruitment of first participant to publication of results was failure to meet recruitment targets, reported by 19 (44%) respondents. A common comment was that this reflected overoptimistic or inaccurate estimates of recruitment at site. Data management, including case report form design and delays in resolving data queries with sites, was reported as an important inefficiency by 11 (26%) respondents, and preparation and submission for publication by 9 (21%). CONCLUSIONS: Recommendations for improving the efficiency of trial conduct within the CTUs network include: further reducing unnecessary bureaucracy in approvals and contracting; improving training for site staff; realistic recruitment targets and appropriate feasibility; developing training across the network; improving the working relationships between chief investigators and units; encouraging funders to release sufficient funding to allow prompt recruitment of trial staff; and encouraging more research into how to improve the efficiency and quality of trial conduct

    Detection of microchromosomal aberrations in refractory epilepsy: a pilot study

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    ABSTRACT -Seizures often occur in patients with microchromosomal aberrations responsible for moderate to severe intellectual disability. We hypothesised that epilepsy alone could be caused by microdeletions or microduplications, which might also relate to epilepsy refractory to medication. Chromosomes from 20 subjects with epilepsy and repeated failure of antiepileptic medication were examined using molecular methods. Firstly, the 41 subtelomeric regions were scanned using fluorescence in situ hybridization and multiplex ligationdependent probe amplification. Secondly, a genome-wide scan was carried out using oligonucleotide-array comparative genome hybridisation on two platforms: Nimblegen and Agilent. Two aberrations (2/20) were identified: a recurrent microdeletion at 15q13.3 previously characterised in patients with seizures that generally respond to medication, and a novel 1.15 Mb microchromosomal duplication at 10q21.2 also present in the unaffected mother. We conclude that gene content of microchromosomal aberrations is not a major cause of refractory seizures, but that microchromosomal anomalies are found in an appreciable fraction of such cases

    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
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