A de novo mutation in the ß-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare hereditary leukoencephalopathy that was originally identified by MRI pattern analysis, and it has thus far defied all attempts at identifying the causal mutation. Only 22 cases are published in the literature to date. We performed exome sequencing on five family trios, two family quartets, and three single probands, which revealed that all eleven H-ABC-diagnosed individuals carry the same de novo single-nucleotide TUBB4A mutation resulting in nonsynonymous change p.Asp249Asn. Detailed investigation of one of the family quartets with the singular finding of an H-ABC-affected sibling pair revealed maternal mosaicism for the mutation, suggesting that rare de novo mutations that are initially phenotypically neutral in a mosaic individual can be disease causing in the subsequent generation. Modeling of TUBB4A shows that the mutation creates a nonsynonymous change at a highly conserved asparagine that sits at the intradimer interface of α-tubulin and ß-tubulin, and this change might affect tubulin dimerization, microtubule polymerization, or microtubule stability. Consistent with H-ABC's clinical presentation, TUBB4A is highly expressed in neurons, and a recent report has shown that an N-terminal alteration is associated with a heritable dystonia. Together, these data demonstrate that a single de novo mutation in TUBB4A results in H-ABC.

Bicycle boulevards and changes in physical activity and active transportation: findings from a natural experiment.

OBJECTIVE: This study evaluates changes in physical activity and active transportation associated with installation of new bicycle boulevards. METHODS: This natural experiment study uses data from a longitudinal panel of adults with children (n=353) in Portland, OR. Activity and active transportation outcomes were measured with GPS and accelerometers worn for up to 5 days in 2010-11 and 2012-13. The effect of the treatment was estimated using difference in differences estimation and multivariate regression models. RESULTS: In five of the seven models, the interaction term was not significant, indicating that after controlling for the main effects of time and exposure separately, there was no correlation between being in a treatment area and minutes of moderate and vigorous physical activity (MVPA) per day, bicycling >10 min, walking >20 min, minutes of walking (if >20), or making a bike trip. Significant covariates included rain, being female, living closer to downtown, and attitudes towards bicycling, walking, and car safety. CONCLUSION: This study could not confirm an increase in physical activity or active transportation among adults with children living near newly installed bicycle boulevards. Additional pre/post studies are encouraged, as well as research on the length of time after installation that behavior change is likely to occur.

The Effect of Implementation of the American Heart Association Mission Lifeline PreAct Algorithm for Prehospital Cardiac Catheterization Laboratory Activation on the Rate of "False Positive" Activations.

HYPOTHESIS: Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of "false positive" prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation. METHODS: This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B. RESULTS: A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B. CONCLUSIONS: The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.

Cancellation of the Cardiac Catheterization Lab After Activation for ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Prehospital ECG-based cardiac catheterization laboratory (CCL) activation for ST-segment-elevation myocardial infarction reduces door-to-balloon times, but CCL cancellations (CCLX) remain a challenging problem. We examined the reasons for CCLX, clinical characteristics, and outcomes of patients presenting as ST-segment-elevation myocardial infarction activations who receive emergent coronary angiography (EA) compared with CCLX. METHODS AND RESULTS: We reviewed all consecutive CCL activations between January 1, 2012, and December 31, 2014 (n=1332). Data were analyzed comparing 2 groups stratified as EA (n=466) versus CCLX (n=866; 65%). Reasons for CCLX included bundle branch block (21%), poor-quality prehospital ECG (18%), non-ST-segment-elevation myocardial infarction ST changes (18%), repolarization abnormality (13%), and arrhythmia (8%). A multivariate logistic regression model using age, peak troponin, and initial ECG findings had a high discriminatory value for determining EA versus CCLX (C statistic, 0.985). CCLX subjects were older and more likely to be women, have prior coronary artery bypass grafting, or a paced rhythm ( P<0.0001 for all). All-cause mortality did not differ between groups at 1 year or during the study period (mean follow-up, 2.186±1.167 years; 15.8% EA versus 16.2% CCLX; P=0.9377). Cardiac death was higher in the EA group (11.8% versus 3.0%; P<0.0001). After adjusting for clinical variables associated with survival, CCLX was associated with an increased risk for all-cause mortality during the study period (hazard ratio, 1.82; 95% CI, 1.28-2.59; P=0.0009). CONCLUSIONS: In this study, prehospital ECG without overreading or transmission lead to frequent CCLX. CCLX subjects differ with regard to age, sex, risk factors, and comorbidities. However, CCLX patients represent a high-risk population, with frequently positive cardiac enzymes and similar short- and long-term mortality compared with EA. Further studies are needed to determine how quality improvement initiatives can lower the rates of CCLX and influence clinical outcomes.

Abdominal Injuries in the "Found Down": Is Imaging Indicated?

BACKGROUND: We sought to investigate the incidence of abdominal injuries in "found down" trauma patients to better understand the value of emergency department (ED) imaging. Found down patients are at high risk for injuries to the head or neck and low risk to the abdomen or pelvis, so imaging with CT of the abdomen/pelvis (AP) or Focused Assessment with Sonography for Trauma (FAST) is of questionable value. STUDY DESIGN: The trauma registry was queried over a 10-year period ending December 2013 for found down patients. Demographics, CT AP, FAST scans, and injuries were abstracted from the trauma registry and then through a confirmatory chart review. The primary outcome was significant abdominal or pelvis injury, defined as abdomen/pelvis Abbreviated Injury Scale (AIS) ≥ 3 or an abdominal injury that required operative intervention. The secondary outcome was mortality due to abdominal injury. RESULTS: Of the 342 patients who met inclusion criteria, mean Glasgow Coma Scale (GCS) was 11.0, and 189 (60%) of those tested for alcohol were intoxicated. Abdominal imaging included: CT AP only, 88 (57%); FAST only, 37 (24%); and CT AP and FAST, 29 (19%). Neither CT AP nor FAST scan led to a change in treatment and no patient had abdomen/pelvis AIS ≥ 3. Overall mortality was 33 (10%).The 24 trauma deaths were attributed to serious head trauma (n = 16) or traumatic arrest in the ED (n = 8); the 9 medical deaths were due to cerebral vascular accident (n = 5) or sepsis (n = 4). CONCLUSIONS: Although patients found down have a high mortality, abdominal injuries identified by imaging are highly unlikely. Efforts should focus on rapidly identifying and treating other causes of mortality, especially trauma to the head and neck, or medical diagnoses such as cerebral vascular accident or sepsis.

Evaluation of bike boxes at signalized intersections.

This paper presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflicts between motor vehicles and cyclists, particularly in potential "right-hook" situations. Before and after video were analyzed for seven intersections with green bike boxes, three intersections with uncolored bike boxes, and two control intersections. User perceptions were measured through surveys of cyclists passing through five of the bike box intersections and of motorists working downtown, where the boxes were concentrated. Both the observations and survey of motorists found a high rate of compliance and understanding of the markings. Overall, 73% of the stopping motor vehicles did not encroach at all into the bike box. Both motor vehicle and bicycle encroachment in the pedestrian crosswalk fell significantly at the bike box locations compared to the control intersections. The bike boxes had mixed effects on the motorists' encroachment in the bicycle lane. The number of observed conflicts at the bike box locations decreased, while the total number of cyclists and motor vehicles turning right increased. Negative-binomial models based upon the data predict fewer conflicts with the boxes, particularly as right-turning motor vehicle volumes increase. Observations of yielding behavior at two bike box and one control intersection found an improvement in motorists yielding to cyclists at the bike box locations. Differences in the traffic volumes and location contexts make firm conclusions about the effects of green coloring of the boxes difficult. Higher shares of surveyed motorists felt that the bike boxes made driving safer rather than more dangerous, even when the sample was narrowed to respondents who were not also cyclists. Over three-quarters of the surveyed cyclists thought that the boxes made the intersection safer.