We employ a stable isotope strategy wherein both histones and their methylations are labeled in synchronized human cells. This allows us to differentiate between old and new methylations on ...pre-existing versus newly synthesized histones. The strategy is implemented on K79 methylation in an isoform-specific manner for histones H3.1, H3.2, and H3.3. Although levels of H3.3K79 monomethylation are higher than that of H3.2/H3.1, the rate of establishing the K79 methylation is the same for all three isoforms. Surprisingly, we find that pre-existing “old” histones continue to be K79-monomethylated and -dimethylated at a rate equal to the newly synthesized histones. These observations imply that some degree of positional “scrambling” of K79 methylation occurs through the cell cycle.
Although more than a dozen states have ratified laws that require booster seats for children older than 4 years, most states continue to have child restraint laws that only cover children through age ...4 years. Lack of booster seat effectiveness data may be a barrier to passage of stronger child restraint laws.
To quantify the association of belt-positioning booster seats compared with seat belts alone and risk of injury among 4- to 7-year-old children and to assess patterns of injury among children in booster seats vs seat belts.
Cross-sectional study of children aged 4 to 7 years in crashes of insured vehicles in 15 states, with data collected via insurance claims records and a telephone survey. A probability sample of 3616 crashes involving 4243 children, weighted to represent 56 593 children in 48 257 crashes was collected between December 1, 1998, and May 31, 2002.
Parent report of clinically significant injuries.
Injuries occurred among 1.81% of all 4- to 7-year-olds, including 1.95% of those in seat belts and 0.77% of those in belt-positioning booster seats. The odds of injury, adjusting for child, driver, crash, and vehicle characteristics, were 59% lower for children aged 4 to 7 years in belt-positioning boosters than in seat belts (odds ratio, 0.41; 95% confidence interval, 0.20-0.86). Children in belt-positioning booster seats had no injuries to the abdomen, neck/spine/back, or lower extremities, while children in seat belts alone had injuries to all body regions.
Belt-positioning booster seats were associated with added safety benefits compared with seat belts to children through age 7 years, including reduction of injuries classically associated with improper seat belt fit in children.
Background New Jersey (NJ) implemented the first Graduated Driver Licensing (GDL) decal provision in the U.S. in May 2010. An initial study reported a 1-year post-decal decrease in the crash rate ...among NJ intermediate drivers aged <21 years. Longer-term analysis is critical for policymakers in other states considering whether to implement a decal provision. Purpose To evaluate the longer-term (2-year) effect of NJ’s decal provision on overall and age-specific crash rates of young drivers with intermediate licenses. Methods Monthly per-driver police-reported crash rates during January 2006–June 2012 were estimated. Specific crash types included injury, midnight–4:59 am , single-vehicle, multiple-vehicle, and peer passenger crashes. Negative binomial modeling compared pre- versus post-decal crash rates, adjusting for age, gender, calendar month, gas price, and 21- to 24-year-old licensed driver crash rates; piecewise negative binomial regression models accounted for pre-decal crash trends among intermediate drivers. Analyses were conducted in 2013. Results The adjusted crash rate for intermediate drivers was 9.5% lower in the 2-year post-decal period than the 4-year pre-decal period (95% CI=0.88, 0.93). Crash rates decreased 1.8% per year before the provision and 7.9% per year in the post-decal period ( p <0.001 for difference in slopes). For several crash types, effects appeared to be particularly strong for 18- and 19-year-olds. An estimated 3,197 intermediate drivers had crashes prevented. Conclusions NJ’s decal provision was associated with a sustained decline in intermediate driver crashes. Future research should aim to better understand the causal mechanism by which NJ’s decal provision may have exerted an effect.
Objective To evaluate pediatricians' self-reported knowledge, attitudes, and dissemination practices regarding the new American Academy of Pediatrics' (AAP) child passenger safety (CPS) policy ...recommendations. Study design A cross-sectional survey was distributed to pediatric primary care physicians via AAP e-mail distribution lists. Knowledge, attitudes, and practices related to current AAP CPS recommendations and the revised policy statement were ascertained. Results There were 718 respondents from 3497 physicians with active e-mail addresses, resulting in a 20.5% response rate, of which 533 were eligible based on the initial survey question. All 6 CPS knowledge and scenario-based items were answered correctly by 52.9% of the sample; these respondents were identified as the “high knowledge” group. Pediatricians with high knowledge were more likely to be female ( P < .001), to have completed a pediatrics residency (vs medicine-pediatrics) ( P = .03), and have a child between 4 and 7 years of age ( P = .001). CPS information was distributed more frequently at routine health visits for patients 0-2 years of age vs those 4-12 years of age. Those with high knowledge were less likely to report several specific barriers to dissemination of CPS information, more likely to allot adequate time and discuss CPS with parents, and had greater confidence for topics related to all CPS topics. Conclusions Although CPS knowledge is generally high among respondents, gaps in knowledge still exist. Knowledge is associated with attitudes, practices, barriers, and facilitators of CPS guideline dissemination. These results identify opportunities to increase knowledge and implement strategies to routinely disseminate CPS information in the primary care setting.
•We examined interactive associations of license age, driving experience, and license phase.•Age at licensure and driving experience interact to influence crash rates.•Benefit of later licensure was ...most apparent in first 6 months of driving.•Benefit of increased experience was greatest for teens licensed immediately after eligible.•Regardless of age or experience, crash rates increase at transition to full license.
Few studies have concurrently assessed the influence of age and experience on young driver crashes, in particular in the post-Graduated Driver Licensing (GDL) era. Further, little attention is given to the transition from intermediate to full licensure. We examined the independent and joint contributions of licensing age, driving experience, and GDL license phase on crash rates among the population of young New Jersey (NJ) drivers.
From a unique linked database containing licensing and crash data, we selected all drivers who obtained their NJ intermediate license at 17–20 years old from 2006–2009 (n=410,230). We determined the exact age at which each driver obtained an intermediate and full license and created distinct, fixed cohorts of drivers based on their age at intermediate licensure. For each cohort, we calculated and graphed observed monthly crash rates over the first 24 months of licensure. Further, we examined crash rates by age at licensure, driving experience (i.e., time since licensure), and license phase.
First-month crash rates were higher among the youngest drivers (licensed at 17y0m). Drivers who were licensed later experienced a reduced “steepness” in the slope of their crash rates in the critical initial months of driving, but there did not appear to be any incremental benefit of later licensure once drivers had six months of driving experience. Further, at each age, those with more driving experience had lower crash rates; however, the benefit of increased experience was greatest for the substantial proportion of teens licensed immediately after becoming eligible (at 17y0m). Finally, independent of age and experience, teen drivers’ crash risk increased substantially at the point of transition to a full license, while drivers of a similar age who remained in the intermediate phase continued to experience a decline in crash rates.
Age and driving experience interact to influence crash rates. Further, independent of these two factors, there is an abrupt increase in crash risk at the point of transition from intermediate to full licensure. Future studies should investigate whether this increase is accounted for by a change in driving exposure, driving behaviors, and/or other factors.
For fractionation of intact proteins by molecular weight (MW), a sharply improved two-dimensional (2D) separation is presented to drive reproducible and robust fractionation before top-down mass ...spectrometry of complex mixtures. The “GELFrEE” (i.e., gel-eluted liquid fraction entrapment electrophoresis) approach is implemented by use of Tris-glycine and Tris-tricine gel systems applied to human cytosolic and nuclear extracts from HeLa S3 cells, to achieve a MW-based fractionation of proteins from 5 to >100 kDa in 1 h. For top-down tandem mass spectroscopy (MS/MS) of the low-mass proteome (5–25 kDa), between 5 and 8 gel-elution (GE) fractions are sampled by nanocapillary-LC-MS/MS with 12 or 14.5 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. Single injections give about 40 detectable proteins, about half of which yield automated ProSight identifications. Reproducibility metrics of the system are presented, along with comparative analysis of protein targets in mitotic versus asynchronous cells. We forward this basic 2D approach to facilitate wider implementation of top-down mass spectrometry and a variety of other protein separation and/or characterization approaches.
Molecular weight-based separation of intact proteins coupled to LC-FTMS/MS facilitated low-mass top-down proteomics. A heat map visualization of LC-MS injections is shown.
Objective To determine the prevalence and nature of residual cognitive disability after inpatient rehabilitation for children aged 7-18 years with traumatic injuries. Study design This retrospective ...cohort study included children aged 7-18 years in the Uniform Data System for Medical Rehabilitation who underwent inpatient rehabilitation for traumatic injuries in 523 facilities from 2002-2011. Traumatic injuries were identified by standardized Medicare Inpatient Rehabilitation Facility–Patient Assessment Instrument codes. Cognitive outcomes were measured by the Functional Independence Measure instrument. A validated, categorical staging system derived from responses to the items in the cognitive domain of the functional independence measure was used and consisted of clinically relevant levels of cognitive achievement from stage 1 (total cognitive disability) to stage 7 (completely independent cognitive function). Results There were 13 798 injured children who completed inpatient rehabilitation during the 10-year period. On admission to inpatient rehabilitation, patients with traumatic brain injury (TBI) had more cognitive disability (median stage 2) than those with spinal cord injury or other injuries (median stage 5). Cognitive functioning improved for all patients, but children with TBI still tended to have significant residual cognitive disability (median stage on discharge, 4). Conclusions Injured children gained cognitive functionality throughout inpatient rehabilitation. Those with TBI had more severe cognitive disability on admission and more residual disability on discharge. This is important not only for patient and family expectation setting but also for resource and service planning, as discharge from inpatient rehabilitation is a critical milestone for reintegration into society for children with serious injury.
The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic ...annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.
There is growing evidence for both the need to manage work-life conflict and the opportunity for mentors to advise their mentees on how to do this in an academic research environment.
A multiphase ...approach was used to develop and implement an evidence-informed training module to help mentors guide their mentees in issues of work-life conflict. Analysis of existing data from a randomized controlled trial (RCT) of a mentor training curriculum (n = 283 mentor/mentee dyads) informed the development of a work-life mentoring module which was incorporated into an established research mentor training curriculum and evaluated by faculty at a single academic medical center.
Only 39% of mentors and 36% of mentees in the RCT indicated high satisfaction with the balance between their personal and professional lives. The majority (75%) of mentors and mentees were sharing personal information as part of the mentoring relationship which was significantly associated with mentees' ratings of the balance between their personal and professional lives. The effectiveness of the work-life module was assessed by 60 faculty mentors participating in a mentor training program at an academic medical center from 2013 to 2017. Among the respondents to the post-training survey, 82.5% indicated they were very/somewhat comfortable addressing work-life issues with their mentees as a result of the training, with significant improvements (p = 0.001) in self-assessments of mentoring skill in this domain.
Our findings indicate that a structured training approach can significantly improve mentors' self-reported skills in addressing work-life issues with their mentees.
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