Abstract
Summary
Large-scale sharing of genomic quantification data requires standardized access interfaces. In this Global Alliance for Genomics and Health project, we developed RNAget, an API for ...secure access to genomic quantification data in matrix form. RNAget provides for slicing matrices to extract desired subsets of data and is applicable to all expression matrix-format data, including RNA sequencing and microarrays. Further, it generalizes to quantification matrices of other sequence-based genomics such as ATAC-seq and ChIP-seq.
Availability and implementation
https://ga4gh-rnaseq.github.io/schema/docs/index.html.
Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds "tracer" levels. Negative bias would also arise in successive PET ...scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant K
of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo K
. This method was applied in a study of healthy human subjects with the histamine H
receptor radioligand
CGSK189254 to measure the PK-occupancy relationship of the H
antagonist PF-03654746. From three test/retest studies,
CGSK189254 K
was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%-97% and 30%-93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%-15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H
binding sites ( RO
= 100%), and its IC
was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC
was 26% higher.
The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, ...diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda.
The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors.
In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions.
The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals.
The first very long baseline interferometry (VLBI) detections at 870 μm wavelength (345 GHz frequency) are reported, achieving the highest diffraction-limited angular resolution yet obtained from the ...surface of the Earth and the highest-frequency example of the VLBI technique to date. These include strong detections for multiple sources observed on intercontinental baselines between telescopes in Chile, Hawaii, and Spain, obtained during observations in 2018 October. The longest-baseline detections approach 11 Gλ, corresponding to an angular resolution, or fringe spacing, of 19 μas. The Allan deviation of the visibility phase at 870 μm is comparable to that at 1.3 mm on the relevant integration timescales between 2 and 100 s. The detections confirm that the sensitivity and signal chain stability of stations in the Event Horizon Telescope (EHT) array are suitable for VLBI observations at 870 μm. Operation at this short wavelength, combined with anticipated enhancements of the EHT, will lead to a unique high angular resolution instrument for black hole studies, capable of resolving the event horizons of supermassive black holes in both space and time.
A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and ...efficacy of OROS MPH in a multicenter, randomized, clinical trial.
Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward.
Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively.
For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.
Graduated autonomy is fundamental as trainees transition to independent practice. Family-centered rounds (FCR), the leading model of inpatient rounding in pediatrics, is an opportunity for trainees ...to demonstrate their competence in leading a health care team, which is an entrustable professional activity for all pediatric residents. At our institution, senior residents (SRs) at baseline performed at a novice level on the basis of the Senior Resident Empowerment Actions 21 (SREA-21), a validated tool that is used to assess SR autonomy during FCR. Our objective for this study was to increase the median percentage of SREA-21 domains in which SRs perform at a competent level from 38% to 75% within 6 months.
Researchers observed 4 FCR encounters weekly and calculated SREA-21 scores after 2 weeks on the basis of actions promoting SR autonomy performed by the SR-hospitalist dyad. The primary outcome measure was the percentage of SREA-21 domains in which the SR achieved a competent score on the SREA-21. We used the model for improvement to identify key drivers and test proposed interventions using serial plan-do-study-act cycles. Interventions included creation of unified inpatient SR expectations, introduction of a SR-hospitalist pre-FCR huddle, auditing of FCR interruptions, and direct feedback to the SR-hospitalist dyad after FCR. Run charts were used to track SR and hospitalist scores on the SREA-21.
After multiple plan-do-study-act cycles, there was special cause improvement with a desirable shift upward in the centerline to 100%, which correlated with the project's interventions and surpassed our goal.
Using quality improvement methodology, we improved SR autonomy during FCR, as measured by the SREA-21.
Few treatment studies of attention-deficit/hyperactivity disorder (ADHD) extend beyond a few months. This article reports an interim analysis of a 24-month study evaluating the 12-month tolerability ...and effectiveness of a once-daily OROS formulation of methylphenidate (OROS MPH) in children with ADHD.
Children, aged 6-13 years, with ADHD who participated in previous controlled studies and were MPH responders, received once-daily OROS MPH in this multicenter, open-label, nonrandomized study. Effectiveness was evaluated monthly by parents/caregivers and schoolteachers using validated rating scales (e.g., IOWA Conners). Safety and adverse events assessments involved objective (e.g., vital signs, growth) and subjective (sleep quality, tics) reporting.
Seventy-one percent of subjects (289/407) completed 12 months' treatment. Effectiveness was maintained throughout 12 months as demonstrated by stable IOWA Conners ratings and sustained improvements in peer interaction and Global Assessment Scale scores. OROS MPH was well tolerated, with adverse events similar to those expected with short-acting stimulant medication. OROS MPH had minimal impact on sleep quality and tics. There were no clinically meaningful changes in blood pressure, pulse, or height. The apparent absence of meaningful changes is tempered by the fact that children were MPH responders and were medicated at baseline, most for extended periods prior to enrollment.
In this open-label study, once-daily OROS MPH treatment appears to be well tolerated and effectiveness was maintained for up to 12 months in these children with ADHD.
To measure the primary and secondary school-age neurologic, cognitive, and educational outcomes in a cohort of extremely premature infants born after the introduction of exogenous surfactant therapy ...in a circumscribed region.
Two hundred thirteen infants born at <29 weeks' gestation were cared for at a regional referral center during 1985-1987. At primary school age, neurologic and cognitive outcomes, educational achievement, school placement, health status, and socioeconomic status were determined by follow-up visit. At secondary school age, school placement and health status were evaluated by telephone interview.
One hundred thirty-two infants survived to school age, of whom 127 (96%) were evaluated in 1992-1995 and 126 (95%) were evaluated in 2000. Mean ages were 7.0 years at first follow-up and 14.1 years at second follow-up. At primary-school age follow-up, 19 children (15%) had cerebral palsy, 24 (19%) had a general cognitive index <70, and 41 (32%) were placed in a self-contained, special classroom. Thirty-nine children (31%) had no physical or educational impairment, whereas 27 (21%) had at least 1 severe disability. At secondary school age, cerebral palsy incidence remained unchanged, whereas 36 children (29%) were placed in a special classroom. Fifty-one children (41%) had no physical or educational impairment, whereas 24 (19%) had at least 1 severe disability. Neonatal intraventricular hemorrhage and low socioeconomic status were the strongest predictors of adverse outcomes.
Premature infants born in the surfactant era remain at high risk of neurodevelopmental compromise. Although many of these children do well, a significant minority will require intensive special educational services through secondary school age.
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