Risk-minimal routes for emergency cars

The computation of an optimal route for given start and destination in a static transportation network is used in many applications of private route planning. In this work we focus on route planning for emergency cars, such as for example police, fire brigade and ambulance. In case of private route planning typical quantities to be minimized are travel time or route length. However, the idea of this paper is to minimize the risk of a travel time exceeding a certain limit. This is inspired by the fact that the emergency cars have to reach the destination within a legal time. We consider mainly two approaches. The first approach takes into account relevant information to determine the weight, i.e. the desirability of certain edges of a graph during the minimization procedure. One possible risk factor to be aware of would be a suddenly jammed single-lane road on which the emergency car has no chance to make use of the benefits of the siren for instance. The same holds for full-closure situations and railroad crossings. We present a catalogue of risk factors along with an appropriate algorithm for practical route planning in emergency situations. The second one takes into account a weekly updated set of probe-vehicle data for each minute of the week along with data of current travel times. Comparing those travel-time data allows calculation of the associated risk for traveling certain edges of a route in a road network. We expect our algorithm to be a major advancement especially for destinations that lie outside the typical region travelled weekdays. In this case the automatic route planning naturally goes along with an additional gain of time

EmerT – a web based decision support tool for Traffic Management

This paper describes the EmerT portal (Emergency mobility of rescue forces and regular Traffic), an extended version of the DELPHI web tool. EmerT is a web decision support application for real time traffic situation, prognosis and traffic simulation. One of the main features in this system is to provide traffic state estimation and forecasts with use of the mesoscopic traffic simulation. Traffic bottlenecks can be identified by the simulation which helps the decision maker to take appropriate traffic management actions. Another feature is the information exchange and cooperation between the Traffic Management Center, Emergency Rescue Services, Police and Emergency Call Center. This application supports three demonstration regions in Germany, Cologne, Bonn and Munich, and will be extended for the whole region of Germany. The main purpose is to handle major incidents and large events which affect changes in the traffic demand and current traffic situation. The EmerT system supports users to get a quick overview of the current traffic situation. This paper aims to present the current development state of the EmerT portal with focus on the backend including traffic simulation, data acquisition and aerial imaging

Successful surgical repair and perioperative management of 6-month-old with total anomalous pulmonary venous return in a developing country: Considerations for the treatment of pulmonary hypertension

Total anomalous pulmonary venous return (TAPVR) is a rare congenital cardiac defect, accounting for 1.5-3% of cases of congenital heart disease. With prenatal ultrasonography, the majority of these patients are diagnosed in utero with definitive surgery performed during the neonatal period. However, as prenatal screening may not be available in developing countries, patients may present in later infancy. We present successful surgical repair of a 6-month-old infant with TAPVR who presented for medical care at 5 months of age in Lima, Peru. The late presentation of such infants and the limited resources available for the treatment of elevated pulmonary vascular resistance may impact successful surgical correction of such defects. The perioperative care of such infants in developing countries is discussed and strategies for managing postoperative pulmonary hypertension is reviewed

Interaction of yeast Rad51 and Rad52 relieves Rad52-mediated inhibition of de novo telomere addition.

DNA double-strand breaks (DSBs) are toxic forms of DNA damage that must be repaired to maintain genome integrity. Telomerase can act upon a DSB to create a de novo telomere, a process that interferes with normal repair and creates terminal deletions. We previously identified sequences in Saccharomyces cerevisiae (SiRTAs; Sites of Repair-associated Telomere Addition) that undergo unusually high frequencies of de novo telomere addition, even when the original chromosome break is several kilobases distal to the eventual site of telomerase action. Association of the single-stranded telomere binding protein Cdc13 with a SiRTA is required to stimulate de novo telomere addition. Because extensive resection must occur prior to Cdc13 binding, we utilized these sites to monitor the effect of proteins involved in homologous recombination. We find that telomere addition is significantly reduced in the absence of the Rad51 recombinase, while loss of Rad52, required for Rad51 nucleoprotein filament formation, has no effect. Deletion of RAD52 suppresses the defect of the rad51Δ strain, suggesting that Rad52 inhibits de novo telomere addition in the absence of Rad51. The ability of Rad51 to counteract this effect of Rad52 does not require DNA binding by Rad51, but does require interaction between the two proteins, while the inhibitory effect of Rad52 depends on its interaction with Replication Protein A (RPA). Intriguingly, the genetic interactions we report between RAD51 and RAD52 are similar to those previously observed in the context of checkpoint adaptation. Forced recruitment of Cdc13 fully restores telomere addition in the absence of Rad51, suggesting that Rad52, through its interaction with RPA-coated single-stranded DNA, inhibits the ability of Cdc13 to bind and stimulate telomere addition. Loss of the Rad51-Rad52 interaction also stimulates a subset of Rad52-dependent microhomology-mediated repair (MHMR) events, consistent with the known ability of Rad51 to prevent single-strand annealing

Correction to “Abietane-Type Diterpenoids Inhibit Protein Tyrosine Phosphatases by Stabilizing an Inactive Enzyme Conformation”

Protein tyrosine phosphatases (PTPs) contribute to a striking variety of human diseases, yet they remain vexingly difficult to inhibit with uncharged, cell-permeable molecules; no inhibitors of PTPs have been approved for clinical use. This study uses a broad set of biophysical analyses to evaluate the use of abietane-type diterpenoids, a biologically active class of phytometabolites with largely nonpolar structures, for the development of pharmaceutically relevant PTP inhibitors. Results of nuclear magnetic resonance analyses, mutational studies, and molecular dynamics simulations indicate that abietic acid can inhibit protein tyrosine phosphatase 1B, a negative regulator of insulin signaling and an elusive drug target, by binding to its active site in a non-substrate-like manner that stabilizes the catalytically essential WPD loop in an inactive conformation; detailed kinetic studies, in turn, show that minor changes in the structures of abietane-type diterpenoids (e.g., the addition of hydrogens) can improve potency (i.e., lower IC50) by 7-fold. These findings elucidate a previously uncharacterized mechanism of diterpenoid-mediated inhibition and suggest, more broadly, that abietane-type diterpenoids are a promising source of structurally diverseand, intriguingly, microbially synthesizablemolecules on which to base the design of new PTP-inhibiting therapeutics

Age at surgery and outcomes following neonatal cardiac surgery: An analysis from the Pediatric Cardiac Critical Care Consortium

Objective: The optimal timing for neonatal cardiac surgery is a potentially modifiable factor that may affect outcomes. We studied the relationship between age at surgery (AAS) and outcomes across multiple hospitals, focusing on neonatal operations where timing appears is not emergency. Methods: We studied neonates ≥37 weeks\u27 gestation and ≥2.5 kg admitted to a treating hospital on or before day of life 2 undergoing selected index cardiac operations. The impact of AAS on outcomes was evaluated across the entire cohort and a standard risk subgroup (ie, free of preoperative mechanical ventilation, mechanical circulatory support, or other organ failure). Outcomes included mortality, major morbidity (ie, cardiac arrest, mechanical circulatory support, unplanned cardiac reintervention, or neurologic complication), and postoperative cardiac intensive care unit and hospital length of stay. Post hoc analyses focused on operations undertaken between day of life 2 and 7. Results: We studied 2536 neonates from 47 hospitals. AAS from day of life 2 through 7 was not associated with risk adjusted mortality or major morbidity among the entire cohort and the standard risk subgroup. Older AAS, although associated with modest increases in postoperative cardiac intensive care unit and hospital length of stay in the entire cohort, was not associated with hospital length of stay in the standard risk subgroup. Conclusions: Among select nonemergency neonatal cardiac operations, AAS between day of life 2 and 7 was not found to be associated with risk adjusted mortality or major morbidity. Although delays in surgical timing may modestly increase preoperative resource use, studies of AAS and outcomes not evident at the time of discharge are needed

Effect of Location on Tracheal Intubation Safety in Cardiac Disease-Are Cardiac ICUs Safer?

OBJECTIVES: Evaluate differences in tracheal intubation-associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in children with underlying cardiac disease. DESIGN: Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children). SETTING: Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016. PATIENTS: Children with medical or surgical cardiac disease who underwent intubation in an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was the rate of any adverse tracheal intubation-associated event. Secondary outcomes were severe tracheal intubation-associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo [interquartile range, 0-6 mo]) compared with noncardiac ICUs (median 3 mo [interquartile range, 1-11 mo]; p\u3c0.001). Tracheal intubation-associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54-1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52-0.97; p = 0.033). Rates of severe tracheal intubation-associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04-1.15; p = 0.002). CONCLUSIONS: In children with underlying cardiac disease, rates of adverse tracheal intubation-associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models