2,899 research outputs found
Random qubit-states and how best to measure them
We consider the problem of measuring a single qubit, known to have been prepared in either a randomly selected pure state or a randomly selected real pure state. We seek the measurements that provide either the best estimate of the state prepared or maximise the accessible information. Surprisingly, any sensible measurement turns out to be optimal. We discuss the application of these ideas to multiple qubits and higher-dimensional systems
Exploiting biological and physical determinants of radiotherapy toxicity to individualise treatment.
This is the final version of the article. It first appeared from the British Institute of Radiology via http://dx.doi.org/10.1259/bjr.20150172The recent advances in radiation delivery can improve tumour control probability and reduce treatment related toxicity. The use of intensity-modulated radiotherapy (IMRT) in particular can reduce normal tissue toxicity, an objective in its own right, and can allow safe dose escalation in selected cases. Ideally IMRT should be combined with image guidance to verify the position of the target, since patients, target and organs at risk can move day-to-day. Daily image guidance scans can be used to identify the position of normal tissue structures, and potentially to compute the daily delivered dose. Fundamentally, it is still the tolerance of the normal tissues which limits radiotherapy dose and therefore tumour control. However, the dose response relationships for both tumour and normal tissues are relatively steep, meaning that small dose differences can translate into clinically relevant improvements. Differences exist between individuals in the severity of toxicity experienced for a given dose of radiotherapy. Some of this difference may be the result of differences between the planned dose and the accumulated dose (DA). However, some may be due to intrinsic differences in radiosensitivity of the normal tissues between individuals. This field has been developing rapidly, with the demonstration of definite associations between genetic polymorphisms and variation in toxicity recently described. It might be possible to identify more resistant patients who would be suitable for dose escalation, as well as more sensitive patients for whom toxicity could be reduced or avoided. Daily differences in delivered dose have been investigated within the VoxTox research programme, using the rectum as an example organ at risk. In prostate cancer patients receiving curative radiotherapy, considerable daily variation in rectal position and dose can be demonstrated, although the median position matches the planning scan well. Overall, in 10 patients, the mean difference between planned and accumulated rectal equivalent uniform doses (EUDs) was -2.7 Gy (5%), and a dose reduction was seen in 7/10 cases. If dose escalation were performed to take rectal dose back to the planned level, this should increase the mean tumour control probability (TCP) (as biochemical progression-free survival) by 5%. Combining radiogenomics with individual estimates of DA might identify almost half of patients undergoing radical radiotherapy who might benefit from either dose escalation, suggesting improved tumour cure, or reduced toxicity, or both.JS is supported by Cancer Research UK through the Cambridge Cancer Centre. NGB is
supported by the NIHR Cambridge Biomedical Research Centre. The VoxTox Research
Programme is funded by Cancer Research UK
External carotid steal and lateral medullary infarction - is there a pathogenetic connection?
Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population
Background
Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry.
Methods
We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects.
Results
The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7).
Conclusion
Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups
Small-scale land use change modelling using transient groundwater levels and salinities as driving factors – An example from a sub-catchment of Australia’s Murray-Darling Basin
This is the final version. Available from Elsevier via the DOI in this record. Data availability:
Data will be made available on requestAlthough land-use change (LUC) can have detrimental environmental impacts, very few studies have explored the idea that changes in groundwater conditions and water management directly influence LU. This study models how water management policies, groundwater quality (as salinity) and availability drive and impact LUC at a small scale. The Angas Bremer (AB) irrigation district (Murray-Darling Basin, Australia) was used as a case study because it provides a rare example of complex and transient groundwater management. The key questions raised were (i) how has LU, more specifically agricultural practices, changed groundwater quality and availability; (ii) how have groundwater conditions (salinity and levels) subsequently driven LUC and influenced policy changes; and, (iii) how have groundwater conditions improved as a consequence of LU and policy changes. Using the newly-developed Patch-generating LU Simulation (PLUS) model, LUC was simulated and driving factors analysed for the period 1949–2014. To the best of our knowledge, PLUS was able to successfully model groundwater-driven LUC at a small, local scale for the first time in the international literature. The results show that (i) LUC driving factors depend on groundwater conditions and extent of policy in place, and (ii) changes in groundwater salinity and levels led to new water management policy, which in turn dictated LU changes where more water-efficient crops were favoured. LUC likely contributed to a recovery of groundwater levels and low salinity, i.e. groundwater improved to pre-development conditions. Groundwater-related driving factors are responsible for 5–12% depending on agricultural land use and phase.Engineering and Physical Sciences Research Counci
Ab-initio Quantum Enhanced Optical Phase Estimation Using Real-time Feedback Control
Optical phase estimation is a vital measurement primitive that is used to
perform accurate measurements of various physical quantities like length,
velocity and displacements. The precision of such measurements can be largely
enhanced by the use of entangled or squeezed states of light as demonstrated in
a variety of different optical systems. Most of these accounts however deal
with the measurement of a very small shift of an already known phase, which is
in stark contrast to ab-initio phase estimation where the initial phase is
unknown. Here we report on the realization of a quantum enhanced and fully
deterministic phase estimation protocol based on real-time feedback control.
Using robust squeezed states of light combined with a real-time Bayesian
estimation feedback algorithm, we demonstrate deterministic phase estimation
with a precision beyond the quantum shot noise limit. The demonstrated protocol
opens up new opportunities for quantum microscopy, quantum metrology and
quantum information processing.Comment: 5 figure
Fungal microbiota from rain water and pathogenicity of Fusarium species isolated from atmospheric dust and rainfall dust
In order to determine the presence of Fusarium spp. in atmospheric dust and rainfall dust, samples were collected during September 2007, and July, August, and October 2008. The results reveal the prevalence of airborne Fusarium species coming from the atmosphere of the South East coast of Spain. Five different Fusarium species were isolated from the settling dust: Fusarium oxysporum, F. solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples were obtained during significant rainfall events in January and February 2009. Using the dilution-plate method, 12 fungal genera were identified from these rainwater samples. Specific analyses of the rainwater revealed the presence of three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Piñonet and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were chosen because they are the main herbaceous crops in Almeria province. The results presented in this work indicate strongly that spores or propagules of Fusarium are able to cross the continental barrier carried by winds from the Sahara (Africa) to crop or coastal lands in Europe. Results show differences in the pathogenicity of the isolates tested. Both hosts showed root rot when inoculated with different species of Fusarium, although fresh weight measurements did not bring any information about the pathogenicity. The findings presented above are strong indications that long-distance transmission of Fusarium propagules may occur. Diseases caused by species of Fusarium are common in these areas. They were in the past, and are still today, a problem for greenhouses crops in AlmerÃa, and many species have been listed as pathogens on agricultural crops in this region. Saharan air masses dominate the Mediterranean regions. The evidence of long distance dispersal of Fusarium spp. by atmospheric dust and rainwater together with their proved pathogenicity must be taken into account in epidemiological studies
Telomerase Efficiently Elongates Highly Transcribing Telomeres in Human Cancer Cells
RNA polymerase II transcribes the physical ends of linear eukaryotic chromosomes into a variety of long non-coding RNA molecules including telomeric repeat-containing RNA (TERRA). Since TERRA discovery, advances have been made in the characterization of TERRA biogenesis and regulation; on the contrary its associated functions remain elusive. Most of the biological roles so far proposed for TERRA are indeed based on in vitro experiments carried out using short TERRA-like RNA oligonucleotides. In particular, it has been suggested that TERRA inhibits telomerase activity. We have exploited two alternative cellular systems to test whether TERRA and/or telomere transcription influence telomerase-mediated telomere elongation in human cancer cells. In cells lacking the two DNA methyltransferases DNMT1 and DNMT3b, TERRA transcription and steady-state levels are greatly increased while telomerase is able to elongate telomeres normally. Similarly, telomerase can efficiently elongate transgenic inducible telomeres whose transcription has been experimentally augmented. Our data challenge the current hypothesis that TERRA functions as a general inhibitor of telomerase and suggest that telomere length homeostasis is maintained independently of TERRA and telomere transcription
Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study
This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of
Technology Centre for Healthcare (MATCH)
Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice
Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge
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