We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz) rhythm ...modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.
Contemporary pulsar-timing experiments have reached a sensitivity level where systematic errors introduced by existing analysis procedures are limiting the achievable science. We have developed ...tempo2, a new pulsar-timing package that contains propagation and other relevant effects implemented at the 1-ns level of precision (a factor of ∼100 more precise than previously obtainable). In contrast with earlier timing packages, tempo2 is compliant with the general relativistic framework of the IAU 1991 and 2000 resolutions and hence uses the International Celestial Reference System, Barycentric Coordinate Time and up-to-date precession, nutation and polar motion models. tempo2 provides a generic and extensible set of tools to aid in the analysis and visualization of pulsar-timing data. We provide an overview of the timing model, its accuracy and differences relative to earlier work. We also present a new scheme for predictive use of the timing model that removes existing processing artefacts by properly modelling the frequency dependence of pulse phase.
The aim of the REMiniscence groups for people with dementia and their family CAREgivers (REMCARE) study was to assess the effectiveness and cost-effectiveness of joint reminiscence groups for people ...with dementia and their family caregivers as compared with usual care.
A multicentre, pragmatic randomised controlled trial with two parallel arms - an intervention group and a usual-care control group - was carried out. A restricted dynamic method of randomisation was used with an overall allocation ratio of 1 : 1, restricted to ensure intervention groups of a viable size. Assessments, blind to treatment allocation, were carried out at baseline, 3 months and 10 months (primary end point).
Most participants were recruited through NHS Memory Clinics and Community Mental Health Teams for older people. Assessments were usually carried out in the person's home, and treatment groups were held in a variety of community settings.
A total of 488 individuals (mean age 77.5 years) with mild to moderate dementia (meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria), who were initially living in the community, and who had a relative or other caregiver maintaining regular contact, who could act as an informant and was willing and able to participate in the intervention, were recruited to the study. Most carers were spouses (71%). A total of 350 dyads completed the study.
The intervention consisted of joint reminiscence groups held weekly for 12 consecutive weeks, followed by monthly maintenance sessions for a further 7 months. The sessions followed a treatment manual, and were led by two trained facilitators in each centre, supported by a number of volunteers. Up to 12 dyads were invited to attend each group.
The primary outcome measures were self-reported quality of life for the person with dementia and psychological distress for the carer General Health Questionnaire-28 item version (GHQ-28). Secondary outcome measures included autobiographical memory and activities of daily living for the person with dementia, carer stress for the carer and mood, relationship quality and service use and costs for both parties.
The intention-to-treat analysis identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes self-reported quality of life in Alzheimer's disease: mean difference 0.07, standard error (SE) 0.65; F = 0.48; p = 0.53. Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a subscale of the GHQ-28 at the 10-month end point (mean difference 1.25, SE 0.5; F = 8.28; p = 0.04). Compliance analyses suggested some benefits for people with dementia who attended more reminiscence sessions; however, carers attending more groups showed increased caregiving stress. Use of health- and social-care services was modest, with no significant difference in service use between conditions. Owing to negligible difference in quality-adjusted life-year gains (derived from European Quality of Life-5 Dimensions) between the conditions the planned full economic analysis was curtailed.
This trial does not provide support for the effectiveness or cost-effectiveness of joint reminiscence groups for people with dementia and their carers. Although there may be some beneficial effects for people with dementia who attend sessions as planned, this must be viewed in the context of raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions.
Current Controlled Trials ISRCTN42430123.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 48. See the HTA programme website for further project information.
Diabet. Med. 27, 249–256 (2010)
This paper systematically reviews the published literature on the economic evidence of diabetic retinopathy screening. Twenty‐nine electronic databases were searched ...for studies published between 1998 and 2008. Internet searches were carried out and reference lists of key studies were hand searched for relevant articles. The key search terms used were ‘diabetic retinopathy’, ‘screening’, ‘economic’ and ‘cost’. The search identified 416 papers of which 21 fulfilled the inclusion criteria, comprising nine cost‐effectiveness studies, one cost analysis, one cost‐minimization analysis, four cost–utility analyses and six reviews. Eleven of the included studies used economic modelling techniques and/or computer simulation to assess screening strategies. To date, the economic evaluation literature on diabetic retinopathy screening has focused on four key questions: the overall cost‐effectiveness of ophthalmic care; the cost‐effectiveness of systematic vs. opportunistic screening; how screening should be organized and delivered; and how often people should be screened. Systematic screening for diabetic retinopathy is cost‐effective in terms of sight years preserved compared with no screening. Digital photography with telemedicine links has the potential to deliver cost‐effective, accessible screening to rural, remote and hard‐to‐reach populations. Variation in compliance rates, age of onset of diabetes, glycaemic control and screening sensitivities influence the cost‐effectiveness of screening programmes and are important sources of uncertainty in relation to the issue of optimal screening intervals. There is controversy in relation to the economic evidence on optimal screening intervals. Further research is needed to address the issue of optimal screening interval, the opportunities for targeted screening to reflect relative risk and the effect of different screening intervals on attendance or compliance by patients.
tempo2 is a new software package for the analysis of pulsar pulse times of arrival. In this paper, we describe in detail the timing model used by tempo2, and discuss limitations on the attainable ...precision. In addition to the intrinsic slow-down behaviour of the pulsar, tempo2 accounts for the effects of a binary orbital motion, the secular motion of the pulsar or binary system, interstellar, Solar system and ionospheric dispersion, observatory motion (including Earth rotation, precession, nutation, polar motion and orbital motion), tropospheric propagation delay, and gravitational time-dilation due to binary companions and Solar system bodies. We believe that the timing model is accurate in its description of predictable systematic timing effects to better than 1 ns, except in the case of relativistic binary systems where further theoretical development is needed. The largest remaining sources of potential error are measurement error, interstellar scattering, Solar system ephemeris errors, atomic clock instability and gravitational waves.
Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their ...embedded behaviour change techniques.
Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price.
We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using 'gamification' (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals.
64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5-22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; r
=0.23) or price (p=0.45; r
=0.10).
Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits) and game content or price. Further research is required to evaluate effective behaviour change techniques and to assess clinical outcomes.
CRD42015029841.
Previous work has identified two families of proteins that transport classical neurotransmitters into synaptic vesicles, but the protein responsible for vesicular transport of the principal ...excitatory transmitter glutamate has remained unknown. We demonstrate that a protein that is unrelated to any known neurotransmitter transporters and that was previously suggested to mediate the Na+-dependent uptake of inorganic phosphate across the plasma membrane transports glutamate into synaptic vesicles. In addition, we show that this vesicular glutamate transporter, VGLUT1, exhibits a conductance for chloride that is blocked by glutamate.
We present the results of a systematic, unbiased search for subpulse modulation of 187 pulsars performed with the Westerbork Synthesis Radio Telescope (WSRT) in the Netherlands at an observing ...wavelength of 21 cm. Using new observations and archival WSRT data we have increased the list of pulsars that show the drifting subpulse phenomenon by 42, indicating that at least one in three pulsars exhibits this phenomenon. The real fraction of pulsars that show the drifting phenomenon is likely to be larger than 55%. The majority of the analysed pulsars show subpulse modulation (170), of which the majority were not previously known to show subpulse modulation and 30 show clear systematic drifting. The large number of new drifters we have found allows us, for the first time, to do meaningful statistics on the drifting phenomenon. We find that the drifting phenomenon is correlated with the pulsar age such that drifting is more likely to occur in older pulsars. Pulsars that drift more coherently seem to be older and have a lower modulation index. There is no significant correlation found between P3 and other pulsar parameters (such as the pulsar age), as has been reported in the past. There is no significant preference of drift direction and the drift direction is not found to be correlated with pulsar parameters. None of the four complexity parameters predicted by different emission models are shown to be inconsistent with the set of modulation indices of our sample of pulsars. Therefore none of the models can be ruled out based on our observations. We also present results on some interesting new individual sources like a pulsar that shows similar subpulse modulation in both the main- and interpulse and six pulsars with opposite drift senses in different components.
Analysis of 10 years of high-precision timing data on the millisecond pulsar PSR J0437-4715 has resulted in a model-independent kinematic distance based on an apparent orbital period derivative, ...image, determined at the 1.5% level of precision (image pc), making it one of the most accurate stellar distance estimates published to date. The discrepancy between this measurement and a previously published parallax distance estimate is attributed to errors in the DE200 solar system ephemerides. The precise measurement of image allows a limit on the variation of Newton's gravitational constant, image yr super(-1). We also constrain any anomalous acceleration along the line of sight to the pulsar to image s super(-1) at 95% confidence, and derive a pulsar mass, image, one of the highest estimates so far obtained.
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