The Jupiter Energetic Particle Detector Instruments (JEDI) on the Juno Jupiter polar-orbiting, atmosphere-skimming, mission to Jupiter will coordinate with the several other space physics instruments ...on the Juno spacecraft to characterize and understand the space environment of Jupiter’s polar regions, and specifically to understand the generation of Jupiter’s powerful aurora. JEDI comprises 3 nearly-identical instruments and measures at minimum the energy, angle, and ion composition distributions of ions with energies from H:20 keV and O: 50 keV to >1 MeV, and the energy and angle distribution of electrons from <40 to >500 keV. Each JEDI instrument uses microchannel plates (MCP) and thin foils to measure the times of flight (TOF) of incoming ions and the pulse height associated with the interaction of ions with the foils, and it uses solid state detectors (SSD’s) to measure the total energy (
E
) of both the ions and the electrons. The MCP anodes and the SSD arrays are configured to determine the directions of arrivals of the incoming charged particles. The instruments also use fast triple coincidence and optimum shielding to suppress penetrating background radiation and incoming UV foreground. Here we describe the science objectives of JEDI, the science and measurement requirements, the challenges that the JEDI team had in meeting these requirements, the design and operation of the JEDI instruments, their calibrated performances, the JEDI inflight and ground operations, and the initial measurements of the JEDI instruments in interplanetary space following the Juno launch on 5 August 2011. Juno will begin its prime science operations, comprising 32 orbits with dimensions 1.1×40 RJ, in mid-2016.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in ...both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.
Objective
To determine whether relationships with gestational age and birthweight centile vary between specific causes of special educational need (SEN).
Design
Retrospective cohort study.
Setting
...Scotland.
Population
A cohort of 407 503 schoolchildren.
Methods
Polytomous logistic regression was used to examine the risk of each cause of SEN across the spectrum of gestation at delivery and birthweight centile, adjusting for potential confounding factors.
Main outcome measures
Crude and adjusted odds ratios and confidence intervals.
Results
Of the 19 821 children with SEN, 557 (2.8%) had sensory impairments, 812 (4.1%) had physical or motor disabilities, 876 (4.4%) had language impairments, 2823 (14.2%) had social, emotional, or behavioural problems, 7018 (35.4%) had intellectual disabilities, 4404 (22.2%) had specific learning difficulties, and 1684 (8.5%) autistic spectrum disorder (ASD). Extreme preterm delivery (at 24–27 weeks of gestation) was a strong predictor of sensory (adjusted OR 23.64, 95% CI 12.03–46.45), physical or motor (adjusted OR 29.69, 95% CI 17.49–50.40), and intellectual (adjusted OR 11.67, 95% CI 8.46–16.10) impairments, with dose relationships across the range of gestation. Similarly, birthweight below the third centile was associated with sensory (adjusted OR 2.85, 95% CI 2.04–3.99), physical or motor (adjusted OR 2.47, 95% CI 1.82–3.37), and intellectual (adjusted OR 2.67, 95% CI 2.41–2.96) impairments. Together, gestation and birthweight centile accounted for 24.0% of SEN arising from sensory impairment, 34.3% arising from physical or motor disabilities, and 26.6% arising from intellectual disabilities. Obstetric factors were less strongly associated with specific learning difficulties and social or emotional problems, and there were no significant associations with ASD.
Conclusions
The association between gestation and birthweight centile and overall risk of SEN is largely driven by very strong associations with sensory, physical or motor impairments, and intellectual impairments.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Digitizing clinical trials Inan, O T; Tenaerts, P; Prindiville, S A ...
NPJ digital medicine,
07/2020, Volume:
3, Issue:
1
Journal Article
Peer reviewed
Open access
Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as ...a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.
This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices ...governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.
Background
High levels of sedentary behaviour have a negative impact on health and well‐being. There is limited evidence on the prevalence and correlates of sedentary behaviour of adults with ...intellectual disabilities (ID).
Methods
A population‐based sample of adults with ID were invited to take part in a comprehensive health check programme. Demographic and health data were collected during a structured interview and physical examination. Screen time was used as a proxy measure of sedentary behaviour. Bivariate and multivariate statistical modelling examined correlates of screen time.
Results
Fifty per cent of the 725 participants reported four or more hours of screen time per day. Male gender, higher levels of intellectual ability, mobility problems, obesity, not having hearing impairment and not having epilepsy were all significantly associated with higher screen time in the final multivariate model (R2 = 0.16; Hosmer–Lemeshow goodness of fit statistic P = 0.36).
Conclusions
This is the first study to publish population‐based data on the prevalence and correlates of sedentary behaviour in adults with ID. Compared with adults who do not have ID, adults with ID have higher levels, and different correlates, of sedentary behaviour. A better understanding of the social context of sedentary behaviour will inform the design of effective behaviour change programmes for adults with ID.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Objectives We describe the development and validation of measures of human papillomavirus (HPV)/HPV vaccination knowledge, fear/anxiety about vaccination, involvement in HPV vaccine ...decision-making, and self-efficacy with regard to getting the vaccine, designed to evaluate the efficacy of an intervention to affect these domains (collectively termed the HAVIQ: HPV Adolescent Vaccine Intervention Questionnaire). Study design Literature search, cognitive interviews and cross-sectional survey. Methods A literature search identified existing items that were modified for the present measures. Experts reviewed draft measures for face and content validity. Cognitive interviews with adolescents were also used to assess content validity. Adolescents completed the measures and an internal reliability analysis of each measure was performed. Results The four experts concurred that the measures had face validity. Cognitive interviews identified items requiring refinement. Content validity was examined with ten experts and was deemed acceptable. There were 1800 adolescents who completed the measures; Cronbach's alpha was >0.6 for three of the four measures. The four final measures are brief, comprising 25 items in total. Conclusions The measures are robustly developed and validity-tested. The HAVIQ may be used in research settings to evaluate adolescents' knowledge and experiences of the process of HPV vaccination in a school-based vaccination programme.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Purpose: The optimal fractionation schedule for radiotherapy of head and neck cancer has been controversial. The objective of this randomized trial was to test the efficacy of hyperfractionation and ...two types of accelerated fractionation individually against standard fractionation.
Methods and Materials: Patients with locally advanced head and neck cancer were randomly assigned to receive radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5 days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1.2 Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3) accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5 days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy; or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5 days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113 patients entered, 1073 patients were analyzable for outcome. The median follow-up was 23 months for all analyzable patients and 41.2 months for patients alive.
Results: Patients treated with hyperfractionation and accelerated fractionation with concomitant boost had significantly better local-regional control (
p = 0.045 and
p = 0.050 respectively) than those treated with standard fractionation. There was also a trend toward improved disease-free survival (
p = 0.067 and
p = 0.054 respectively) although the difference in overall survival was not significant. Patients treated with accelerated fractionation with split had similar outcome to those treated with standard fractionation. All three altered fractionation groups had significantly greater acute side effects compared to standard fractionation. However, there was no significant increase of late effects.
Conclusions: Hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally advanced head and neck cancer. Acute but not late effects are also increased.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Regulation of the elongation phase of RNA polymerase II transcription by P-TEFb is a critical control point for gene expression. The activity of P-TEFb is regulated, in part, by reversible ...association with one of two HEXIMs and the 7SK snRNP. A recent proteomics survey revealed that P-TEFb and the HEXIMs are tightly connected to two previously-uncharacterized proteins, the methyphosphate capping enzyme, MEPCE, and a La-related protein, LARP7. Glycerol gradient sedimentation analysis of lysates from cells treated with P-TEFb inhibitors, suggested that the 7SK snRNP reorganized such that LARP7 and 7SK remained associated after P-TEFb and HEXIM1 were released. Immunodepletion of LARP7 also depleted most of the 7SK regardless of the presence of P-TEFb, HEXIM or hnRNP A1 in the complex. Small interfering RNA knockdown of LARP7 in human cells decreased the steady-state level of 7SK, led to an initial increase in free P-TEFb and increased Tat transactivation of the HIV-1 LTR. Knockdown of LARP7 or 7SK ultimately caused a decrease in total P-TEFb protein levels. Our studies have identified LARP7 as a 7SK-binding protein and suggest that free P-TEFb levels are determined by a balance between release from the large form and reduction of total P-TEFb.
PDF
