29 research outputs found
Enhancing environmental engagement with natural language interfaces for in-vehicle navigation systems
Four on-road studies were conducted in the Clifton area of Nottingham, UK, aiming to explore the relationships between driver workload and environmental engagement associated with ‘active’ and ‘passive’ navigation systems. In a between-subjects design, a total of 61 experienced drivers completed two experimental drives comprising the same three routes (with overlapping sections), staged one week apart. Drivers were provided with the navigational support of a commercially-available navigation device (‘satnav’), an informed passenger (a stranger with expert route knowledge), a collaborative passenger (an individual with whom they had a close, personal relationship) or a novel interface employing conversational natural language NAV-NLI). The NAV-NLI was created by curating linguistic intercourse extracted from the earlier conditions, and delivering this using a Wizard-of-Oz technique. The different navigational methods were notable for their varying interactivity and the preponderance of environmental landmark information within route directions. Participants experienced the same guidance on each of the two drives to explore changes in reported and observed behaviour. Results show that participants who were more active in the navigation task (collaborative passenger or NAV-NLI) demonstrated enhanced environmental engagement (landmark recognition, route-learning and survey knowledge) allowing them to reconstruct the route more accurately post-drive, compared to drivers using more passive forms of navigational support (SatNav or informed passenger). Workload measures (TDT, NASA-TLX) indicated no differences between conditions, although satnav users and collaborative passenger drivers reported lower workload during their second drive. The research demonstrates clear benefits and potential for a navigation system employing two-way conversational language to deliver instructions. This could help support a long-term perspective in the development of spatial knowledge, enabling drivers to become less reliant on the technology and begin to re-establish associations between viewing an environmental feature and the related navigational manoeuvre
Driven to discussion: engaging drivers in conversation with a digital assistant as a countermeasure to passive task-related fatigue
Using a Wizard-of-Oz approach, we explored the effectiveness of engaging drivers in conversation with a digital assistant as an operational strategy to combat the symptoms of passive task-related fatigue. Twenty participants undertook two 30-minute drives in a medium-fidelity driving simulator between 13:00 and 16:30, when circadian and homeostatic influences naturally reduce alertness. Participants were asked to follow a lead-car travelling at a constant speed of 68mph, in a sparsely-populated UK motorway scenario. During one of the counterbalanced drives, participants were engaged in conversation by a digital assistant (‘Vid’). Results show that interacting with Vid had a positive effect on driving performance and arousal, evidenced by better lane-keeping, earlier response to a potential hazard situation, larger pupil diameter, and an increased spread of attention to the road-scene (i.e. fewer fixations concentrated on the road-centre indicating a lower incidence of ‘cognitive tunnelling’). Drivers also reported higher levels of alertness and lower sleepiness following the Vid drive. Subjective workload ratings suggest that drivers exerted less effort to ‘stay awake’ when engaged with Vid. The findings support the development and application of in-vehicle natural language interfaces, and can be used to inform the design of novel countermeasures for driver fatigue
Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers
<p>Abstract</p> <p>Background</p> <p>This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA.</p> <p>Methods</p> <p>Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance.</p> <p>Results</p> <p>Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P.</p> <p>Conclusions</p> <p>Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.</p
Driver-passenger collaboration as a basis for human-machine interface design for vehicle navigation systems
Human Factors concerns exist with vehicle navigation systems, particularly relating to the effects of current Human-Machine Interfaces (HMIs) on driver disengagement from the environment. A road study was conducted aiming to provide initial input for the development of intelligent HMIs for in-vehicle systems, using the traditional collaborative navigation relationship between the driver and passenger to inform future design. Sixteen drivers navigated a predefined route in the city of Coventry, UK with the assistance of an existing vehicle navigation system (SatNav), whereas a further 16 followed the navigational prompts of a passenger who had been trained along the same route. Results found that there were no significant differences in the number of navigational errors made on route for the two different methods. However, drivers utilising a collaborative navigation approach had significantly better landmark and route knowledge than their SatNav counterparts. Analysis of individual collaborative transcripts revealed the large individual differences in descriptor use by passengers and reference to environmental landmarks, illustrating the potential for the replacement of distance descriptors in vehicle navigation systems. Results are discussed in the context of future HMIs modelled on a collaborative navigation relationship
Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing
Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC50 = 4.5 nM) compared with vorinostat (VOR; EC50 = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC50 = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 μM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART
Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts
Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication