212 research outputs found
E-Voting in an ubicomp world: trust, privacy, and social implications
The advances made in technology have unchained the user from the desktop into interactions where access is anywhere, anytime. In addition, the introduction of ubiquitous computing (ubicomp) will see further changes in how we interact with technology and also socially. Ubicomp evokes a near future in which humans will be surrounded by “always-on,” unobtrusive, interconnected intelligent objects where information is exchanged seamlessly. This seamless exchange of information has vast social implications, in particular the protection and management of personal information. This research project investigates the concepts of trust and privacy issues specifically related to the exchange of e-voting information when using a ubicomp type system
Impact of motor fluctuations on real-life gait in Parkinson’s patients
Background people with PD (PWP) have an increased risk of becoming inactive. Wearable sensors can provide insights into daily physical activity and walking patterns. Research questions (1) is the severity of motor fluctuations associated with sensor-derived average daily walking quantity? (2) is the severity of motor fluctuations associated with the amount of change in sensor-derived walking quantity after levodopa intake? Methods 304 Dutch PWP from the Parkinson@Home study were included. At baseline, all participants received a clinical examination. During the follow-up period (median: 97 days; 25-Interquartile range-IQR: 91 days, 75-IQR: 188 days), participants used the Fox Wearable Companion app and streamed smartwatch accelerometer data to a cloud platform. The first research question was assessed by linear regression on the sensor-derived mean time spent walking/day with the severity of fluctuations (MDS-UPDRS item 4.4) as independent variable, controlled for age and MDS-UPDRS part-III score. The second research question was assessed by linear regression on the sensor-derived mean post-levodopa walking quantity, with the sensor-derived mean pre-levodopa walking quantity and severity of fluctuations as independent variables, controlled for mean time spent walking per day, age and MDS-UPDRS part-III score. Results PWP spent most time walking between 8am and 1pm, summing up to 72 ± 39 (mean ± standard deviation) minutes of walking/day. The severity of motor fluctuations did not influence the mean time spent walking (B = 2.4 ± 1.9, p = 0.20), but higher age (B = −1.3 ± 0.3, p = < 0.001) and greater severity of motor symptoms (B = −0.6 ± 0.2, p < 0.001) was associated with less time spent walking (F(3,216) = 14.6, p<.001, R2 =.17). The severity of fluctuations was not associated with the amount of change in time spent walking in relation to levodopa intake in any part of the day. Significance Analysis of sensor-derived gait quantity suggests that the severity of motor fluctuations is not associated with changes in real-life walking patterns in mildly to moderate affected PWP
Ligand-induced conformational changes in a SMALP-encapsulated GPCR.
The adenosine 2A receptor (A2AR), a G-protein-coupled receptor (GPCR), was solubilised and purified encapsulated in styrene maleic acid lipid particles (SMALPs). The purified A2AR-SMALP was associated with phospholipids characteristic of the plasma membrane of Pichia pastoris, the host used for its expression, confirming that the A2AR-SMALP encapsulated native lipids. The fluorescence spectrum of the A2AR-SMALP showed a characteristic broad emission peak at 330 nm, produced by endogenous Trp residues. The inverse agonist ZM241385 caused 30% increase in fluorescence emission, unusually accompanied by a red-shift in the emission wavelength. The emission spectrum also showed sub-peaks at 321 nm, 335 nm and 350 nm, indicating that individual Trp inhabited different environments following ZM241385 addition. There was no effect of the agonist NECA on the A2AR-SMALP fluorescence spectrum. Substitution of two Trp residues by Tyr suggested that ZM241385 affected the environment and mobility of Trp2466.48 in TM6 and Trp2687.33 at the extracellular face of TM7, causing transition to a more hydrophobic environment. The fluorescent moiety IAEDANS was site-specifically introduced at the intracellular end of TM6 (residue 2316.33) to report on the dynamic cytoplasmic face of the A2AR. The inverse agonist ZM241385 caused a concentration-dependent increase in fluorescence emission as the IAEDANS moved to a more hydrophobic environment, consistent with closing the G-protein binding crevice. NECA generated only 30% of the effect of ZM241385. This study provides insight into the SMALP environment; encapsulation supported constitutive activity of the A2AR and ZM241385-induced conformational transitions but the agonist NECA generated only small effects
The frequency distribution of presenting symptoms in children aged six months to six years to primary care.
Primary care providers and researchers wishing to estimate study recruitment rates need estimates of illness frequency in primary care. Previous studies of children's symptoms have found that presentations are most common for the symptoms: cough, fever, earache, rash, diarrhoea and vomiting. Since 2000, primary care provision in the United Kingdom has changed with the introduction of Walk-in-Centres (WICs) and new Out of Hours (OoHs) providers. To describe the type and frequency of parent-reported presenting symptoms at a range of primary care sites between 2005 and 2007. Parent-reported presenting symptoms, recorded in their own words, were extracted from data collected from all children aged six months to six years during recruitment to a randomised controlled trial. Presenting symptoms were coded and presented as frequency per 100 'consulting sessions' by type of primary care site. Results were evaluated from 2491 episodes of illness at 35 sites. When grouped by primary care site, respiratory symptoms were the most common at OoHs centres, the WIC and general practitioner (GP) surgeries. Trauma symptoms were common in the Emergency Department, but unexpectedly, diarrhoea and vomiting were more common in the Emergency Department and skin presenting symptoms more common at the WIC than at GP sites. We report the relative frequency of acute symptoms by type of primary care provider. These data may be useful to those planning recruitment to primary care paediatric studies and policy makers for planning primary care service provision
Polymerase chain reaction on a viral nanoparticle
The field of synthetic biology includes studies that aim to develop new materials and devices from biomolecules. In recent years much work has been carried out using a range of biomolecular chassis including α-helical coiled coils, α-sheet amyloids and even viral particles. In this work we show how hybrid bionanoparticles can be produced from a viral M13 bacteriophage scaffold through conjugation to DNA primers that can template a polymerase chain reaction (PCR). This unprecedented example of a PCR on a virus particle has been studied by flow aligned linear dichroism spectroscopy, which gives information on the structure of the product as well as a new protototype methodology for DNA detection. We propose that this demonstration of PCR on the surface of a bionanoparticle is a useful addition to ways in which hybrid assemblies may be constructed using synthetic biology
Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough
Objective To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing.
Design Primary care feasibility cluster randomised controlled trial.
Setting 32 general practices in South West England recruiting children from October 2014 to April 2015.
Participants Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI).
Intervention A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record.
Controls Usual practice, with clinicians recording data on symptoms, signs and treatment decisions.
Results Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children’s RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm.
Conclusion Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records
Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder, controls, and PD
OBJECTIVE: We sought to identify motor features that would allow the delineation of individuals with sleep study-confirmed idiopathic REM sleep behavior disorder (iRBD) from controls and Parkinson disease (PD) using a customized smartphone application. METHODS: A total of 334 PD, 104 iRBD, and 84 control participants performed 7 tasks to evaluate voice, balance, gait, finger tapping, reaction time, rest tremor, and postural tremor. Smartphone recordings were collected both in clinic and at home under noncontrolled conditions over several days. All participants underwent detailed parallel in-clinic assessments. Using only the smartphone sensor recordings, we sought to (1) discriminate whether the participant had iRBD or PD and (2) identify which of the above 7 motor tasks were most salient in distinguishing groups. RESULTS: Statistically significant differences based on these 7 tasks were observed between the 3 groups. For the 3 pairwise discriminatory comparisons, (1) controls vs iRBD, (2) controls vs PD, and (3) iRBD vs PD, the mean sensitivity and specificity values ranged from 84.6% to 91.9%. Postural tremor, rest tremor, and voice were the most discriminatory tasks overall, whereas the reaction time was least discriminatory. CONCLUSIONS: Prodromal forms of PD include the sleep disorder iRBD, where subtle motor impairment can be detected using clinician-based rating scales (e.g., Unified Parkinson's Disease Rating Scale), which may lack the sensitivity to detect and track granular change. Consumer grade smartphones can be used to accurately separate not only iRBD from controls but also iRBD from PD participants, providing a growing consensus for the utility of digital biomarkers in early and prodromal PD
The inter-observer agreement of examining pre-school children with acute cough: a nested study
BACKGROUND: The presence of clinical signs have implications for diagnosis, prognosis and treatment. Therefore, the aim of this study was to examine the inter-observer agreement of clinical signs in pre-school children presenting to primary care. METHODS: A nested study comparing two clinical assessments within a prospective cohort of 256 pre-school children with acute cough recruited from eight general practices in Leicestershire, UK. We examined agreement (using kappa statistics) between unstandardised and standardised clinical assessments of tachypnoea, chest signs and fever. RESULTS: Kappa values were poor or fair for all clinical signs (range 0.12 to 0.39) with chest signs the most reliable. CONCLUSIONS: Primary care clinicians should be aware that clinical signs may be unreliable when making diagnosis, prognosis and treatment decisions in pre-school children with cough. Future research should aim to further our understanding of how best to identify abnormal clinical signs
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