917 research outputs found

    The impact of consent on observational research: a comparison of outcomes from consenters and non consenters to an observational study

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    Background Public health benefits from research often rely on the use of data from personal medical records. When neither patient consent nor anonymisation is possible, the case for accessing such records for research purposes depends on an assessment of the probabilities of public benefit and individual harm. Methods In the late 1990s, we carried out an observational study which compared the care given to affluent and deprived women with breast cancer. Patient consent was not required at that time for review of medical records, but was obtained later in the process prior to participation in the questionnaire study. We have re-analysed our original results to compare the whole sample with those who later provided consent. Results Two important findings emerged from the re-analysis of our data which if presented initially would have resulted in insufficient and inaccurate reporting. Firstly, the reduced dataset contains no information about women presenting with locally advanced or metastatic cancer and we would have been unable to demonstrate one of our initial key findings: namely a larger number of such women in the deprived group. Secondly, our re-analysis of the consented women shows that significantly more women from deprived areas (51 v 31%, p = 0.018) received radiotherapy compared to women from more affluent areas. Previously published data from the entire sample demonstrated no difference in radiotherapy treatment between the affluent and deprived groups. Conclusion The risk benefit assessment made regarding the use of medical records without consent should include the benefits of obtaining research evidence based on 100% of the population and the possibility of inappropriate or insufficient findings if research is confined to consented populations

    Formal and model driven design of the bright light therapy system Luxamet

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    Seasonal depression seriously diminishes the quality of life for many patients. To improve their condition, we propose LUXAMET, a bright light therapy system. This system has the potential to relieve patients from some of the symptoms caused by seasonal depression. The system was designed with a formal and model driven design methodology. This methodology enabled us to minimize systemic hazards, like blinding patients with an unhealthy dose of light. This was achieved by controlling race conditions and memory leaks, during design time. We prove that the system specification is deadlock as well as livelock free and there are no invariant violations. These proofs, together with the similarity between specification model and implementation code, make us confident that the implemented system is a reliable tool which can help patients during seasonal depression

    Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

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    Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon

    The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

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    Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

    Extracting the Distribution Amplitudes of the rho meson from the Color Glass Condensate

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    We extract the leading twist-2 and subleading twist-3 Distribution Amplitudes (DAs) of the rho meson using the HERA data on diffractive rho photoproduction. We do so using several Colour Glass Condensate (CGC) inspired and a Regge inspired dipole models. We find that our extracted twist-2 DA is not much model dependent and is consistent with QCD Sum Rules and lattice predictions. The extracted twist-3 DA is more model dependent but is still consistent with the Sum Rules prediction.Comment: 21 pages, 10 figures, 3 tables. Section 6 revised, figures 8 and 9 and table 3 updated. Conclusions essentially unchange

    Inclusive top-pair production phenomenology with TOPIXS

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    We discuss various aspects of inclusive top-quark pair production based on TOPIXS, a new, flexible program that computes the production cross section at the Tevatron and LHC at next-to-next-to-leading logarithmic accuracy in soft and Coulomb resummation, including bound-state effects and the complete next-to-next-to-leading order result in the q-qbar channel, which has recently become available. We present the calculation of the top-pair cross section in pp collisions at 8 TeV centre-of-mass energy, as well as the cross sections for hypothetical heavy quarks in extensions of the standard model. The dependence on the parton distribution input is studied. Further we investigate the impact of LHC top cross section measurements at sqrt(s)=7 TeV on global fits of the gluon distribution using the NNPDF re-weighting method.Comment: 27 pages, 5 figures; v2: corrected typos in Eqs. (2.8) and (6.2) and the text, added footnote on page 4, matches published versio

    Size and shape constancy in consumer virtual reality

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    With the increase in popularity of consumer virtual reality headsets, for research and other applications, it is important to understand the accuracy of 3D perception in VR. We investigated the perceptual accuracy of near-field virtual distances using a size and shape constancy task, in two commercially available devices. Participants wore either the HTC Vive or the Oculus Rift and adjusted the size of a virtual stimulus to match the geometric qualities (size and depth) of a physical stimulus they were able to refer to haptically. The judgments participants made allowed for an indirect measure of their perception of the egocentric, virtual distance to the stimuli. The data show under-constancy and are consistent with research from carefully calibrated psychophysical techniques. There was no difference in the degree of constancy found in the two headsets. We conclude that consumer virtual reality headsets provide a sufficiently high degree of accuracy in distance perception, to allow them to be used confidently in future experimental vision science, and other research applications in psychology

    Changing Epidemiology of Serious Bacterial Infections in Febrile Infants without Localizing Signs

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    Objective: Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time. Patients and Methods: We performed a retrospective review of all infants meeting FWLS criteria at our institution from 1997–2006. We examined all clinical and outcome data and performed statistical analysis of SBI rates and ampicillin resistance rates. Results: 668 infants met criteria for FWLS. The overall rate of SBIs was 10.8%, with a significant increase from 2002–2006 (52/ 361, 14.4%) compared to 1997–2001 (20/307, 6.5%) (p = 0.001). This increase was driven by an increase in E. coli urinary tract infections (UTI), particularly in older infants (31–90 days). Conclusions: We observed a significant increase in E. coli UTI among FWLS infants with high rates of ampicillin resistance. The reasons are likely to be multifactorial, but the results themselves emphasize the need to examine urine in all febrile infants,90days and consider local resistance patterns when choosing empiric antibiotics
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