Mapping the dynamic transfer functions of eukaryotic gene regulation.

Biological information can be encoded within the dynamics of signaling components, which has been implicated in a broad range of physiological processes including stress response, oncogenesis, and stem cell differentiation. To study the complexity of information transfer across the eukaryotic promoter, we screened 119 dynamic conditions-modulating the pulse frequency, amplitude, and pulse width of light-regulating the binding of an epigenome editor to a fluorescent reporter. This system revealed tunable gene expression and filtering behaviors and provided a quantification of the limit to the amount of information that can be reliably transferred across a single promoter as ∼1.7 bits. Using a library of over 100 orthogonal chromatin regulators, we further determined that chromatin state could be used to tune mutual information and expression levels, as well as completely alter the input-output transfer function of the promoter. This system unlocks the information-rich content of eukaryotic gene regulation.

Outcomes After Pediatric Out-of-Hospital Cardiopulmonary Interventions.

OBJECTIVE: The aim of the study was to evaluate outcomes after pediatric out-of-hospital cardiopulmonary interventions (CPIs) by emergency medical services (EMS). METHODS: Children (age, ≤18 years) who received CPI by EMS from 2001 to 2008 were identified from the Utah Department of Health. Cardiopulmonary intervention was defined as oxygenation, ventilation or CPR, and transport to a hospital by EMS. Univariate and multivariable regression analyses evaluated associations between potential predictors and outcomes (death and new neurologic dysfunction). RESULTS: A total of 464 patients (58% male) received EMS attention. For the 71% patients (327) who were alive on EMS arrival, 63% (205) received CPI without CPR. Of note, 6% (12) of these patients died after arrival to the hospital and new neurologic dysfunction was diagnosed in 6% (13). Among the 12 patients who died, 50% (6) were younger than 1 year.On multivariable regression analysis, factors associated with increased risk of death before and in-hospital are the following: age younger than 1 year (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.17-0.39), shorter EMS transport time (OR, 0.94; 95% CI, 0.89-0.99), and longer EMS dispatch time (OR, 1.23; 95% CI, 1.08-1.40). Factors associated with increased risk of new neurologic dysfunction are the following: lack of pulse (OR, 0.14; 95% CI, 0.04-0.53), requiring CPR (OR, 6.15; 95% CI, 1.48-25.6), and CPR duration (OR, 1.20; 95% CI, 1.05-1.37). CONCLUSIONS: Age younger than 1 year, shorter transport time, and longer dispatch time were associated with increased risk of death. Being pulseless upon discovery and receiving CPR were associated with new neurologic dysfunction. Maximizing EMS transport interventions for patients younger than 1 year requiring CPI may improve patient outcomes.

Factors Associated With Resource Utilization and Coronary Artery Dilation in Refractory Kawasaki Disease (from the Pediatric Health Information System Database).

Management guidelines for refractory Kawasaki disease (KD) are vague. We sought to assess practice variation and identify factors associated with large/complex coronary artery aneurysms (LCAA) and resource utilization in refractory KD. This retrospective cohort study identified patients aged ≤18 years with KD (2004 to 2014) using the Pediatric Health Information System. Refractory KD was defined as receiving >1 dose of intravenous immunoglobulin. Demographics, medications, concomitant infections, length of stay (LOS), and charges were collected. Antithrombotic therapy was a surrogate for LCAA. LOS and hospital charges assessed resource utilization. Multivariate regression identified factors associated with LOS, charges, and LCAA. Of 14,194 patients with KD, 2,974 (21%) had refractory KD and 203 of those 2,974 (7%) had LCAA. Additional intravenous immunoglobulin was the sole medication in 77%. Other medications added were steroids (18%), infliximab (2%), and both (3%). Warfarin, low-molecular-weight heparin, tissue plasminogen activator, and clopidogrel were prescribed with equal frequency (2%). Male gender (adjusted relative risk 1.52, 95% confidence interval [CI] 1.08 to 2.16, p <0.01), admission to an intensive care unit (4.79, 95% CI 3.40 to 6.74, p <0.001), arrhythmia (3.00, 95% CI 1.94 to 4.65, p <0.001), and concomitant viral infection (2.29, 95% CI 1.49 to 3.52, p <0.001) were associated with LCAA. Severe illness, race, region, and payer were independently associated with increased charges (p <0.05 for all). In conclusion, treatment for refractory KD varies widely. Concomitant viral infection was associated with a greater risk of LCAA in refractory KD. Better understanding of optimal management may improve outcomes and decrease both variability in management and resource utilization for refractory KD.