Influence of Blind Spot Assistance Systems in Heavy Commercial Vehicles on Accident Reconstruction.

Accidents between right-turning commercial vehicles and crossing vulnerable road users (VRUs) in urban environments often lead to serious or fatal injuries and therefore play a significant role in forensic accident analysis. To reduce the risk of accidents, blind spot assistance systems have been installed in commercial vehicles for several years, among other things, to detect VRUs and warn the driver in time. However, since such systems cannot reliably prevent all turning accidents, an investigation by experts must clarify how the accident occurred and to what extent the blind spot assistance system influenced the course of the accident. The occurrence of the acoustic warning message can be defined as an objective reaction prompt for the driver, so that the blind spot assistance system can significantly influence the avoidability assessment. In order to be able to integrate the system into forensic accident analysis, a precise knowledge of how the system works and its limitations is required. For this purpose, tests with different systems and accident constellations were conducted and evaluated. It was found that the type of sensor used for the assistance systems has a great influence on the system's performance. The lateral distance between the right side of the commercial vehicle and the VRU, as well as obstacles between them, along with the speed difference can have great influence on the reliability of the assistance system. Depending on the concrete time of the system's warning signal, the accident can be avoided or not by the driver when reacting to this signal.

Microstates in complex and dynamical environments: Unraveling situational awareness in critical helicopter landing maneuvers.

Understanding decision-making in complex and dynamic environments is relevant for designing strategies targeting safety improvements and error rate reductions. However, studies evaluating brain dynamics in realistic situations are scarce in the literature. Given the evidence that specific microstates may be associated with perception and attention, in this work we explored for the first time the application of the microstate model in an ecological, dynamic and complex scenario. More specifically, we evaluated elite helicopter pilots during engine-failure missions in the vicinity of the so called "dead man's curve," which establishes the operational limits for a safe landing after the execution of a recovery maneuver (autorotation). Pilots from the Brazilian Air Force flew a AS-350 helicopter in a certified aerodrome and physiological sensor data were synchronized with the aircraft's flight test instrumentation. We assessed these neural correlates during maneuver execution, by comparing their modulations and source reconstructed activity with baseline epochs before and after flights. We show that the topographies of our microstate templates with 4, 5, and 6 classes resemble the literature, and that a distinct modulation characterizes decision-making intervals. Moreover, the source reconstruction result points to a differential activity in the medial prefrontal cortex, which is associated to emotional regulation circuits in the brain. Our results suggest that microstates are promising neural correlates to evaluate realistic situations, even in a challenging and intrinsically noisy environment. Furthermore, it strengthens their usage and expands their application for studying cognition under more realistic conditions.

Short Time Interval Between Neurologic Event and Carotid Surgery Is Not Associated With an Increased Procedural Risk.

BACKGROUND AND PURPOSE: Guidelines recommend that carotid endarterectomy should be performed within 2 weeks in patients with a symptomatic carotid stenosis. Because a Swedish register study indicated that patients treated within the first days after a stroke or transient ischemic attack might have an increased perioperative stroke and mortality risk, this study aimed to find out whether these findings are also true under everyday conditions in Germany. METHODS: Secondary data analysis including 56 336 elective carotid endarterectomy procedures performed for symptomatic carotid stenosis under everyday conditions between 2009 and 2014. The patient cohort was divided into 4 groups according to time interval between index event and surgery (I: 0-2, II: 3-7, III: 8-14, and IV: 14-180 days). Primary outcome was any in-hospital stroke or death. For risk-adjusted analyses, a multilevel multivariable regression model was used. RESULTS: Mean patients' age was 71.1±9.6 years; 67.5% were men. Overall rate of any stroke or death was 2.5% (n=1434). Risk of any in-hospital stroke or death was 3.0% in group I, 2.5% in group II, 2.6% in group III, and 2.3% in group IV. Multivariable regression analysis revealed that the time interval was not significantly associated with the primary outcome. CONCLUSIONS: The time interval between the index event and carotid endarterectomy was not associated with the risk of any in-hospital stroke or death in patients with symptomatic carotid stenosis in Germany. In clinically stable patients, carotid endarterectomy might, therefore, be performed safely as soon as possible after the neurological index event.

Evaluation of Different Blood Collection Tubes and Blood Storage Conditions for the Preservation and Stability of Cell-Free Circulating DNA for the Analysis of the Methylated mSEPT9 Colorectal Cancer Screening Marker.

For the subsequent analysis of the methylated mSEPT9 colorectal cancer screening marker in plasma, different blood collection tubes and blood storage conditions were investigated. The study demonstrated that methylated Septin 9 (mSEPT9) can be consistently detected in plasma samples derived from whole blood samples collected with S-Monovette® K3E and BD Vacutainer ® K2EDTA tubes stored at 2-8 °C for a maximum of 24 h and for samples collected in S-Monovette CPDA tubes stored at 18-25 °C for up to 48 h.

Temporal trends in fetal mortality at and beyond term and induction of labor in Germany 2005-2012: data from German routine perinatal monitoring.

PURPOSE: While a variety of factors may play a role in fetal and neonatal deaths, postmaturity as a cause of stillbirth remains a topic of debate. It still is unclear, whether induction of labor at a particular gestational age may prevent fetal deaths. METHODS: A multidisciplinary working group was granted access to the most recent set of relevant German routine perinatal data, comprising all 5,291,011 hospital births from 2005 to 2012. We analyzed correlations in rates of induction of labor (IOL), perinatal mortality (in particular stillbirths) at different gestational ages, and fetal morbidity. Correlations were tested with Pearson's product-moment analysis (α = 5 %). All computations were performed with SPSS version 22. RESULTS: Induction rates rose significantly from 16.5 to 21.9 % (r = 0.98; p < 0.001). There were no significant changes in stillbirth rates (0.28-0.35 per 100 births; r = 0.045; p = 0.806). Stillbirth rates 2009-2012 remained stable in all gestational age groups irrespective of induction. Fetal morbidity (one or more ICD-10 codes) rose significantly during 2005-2012. This was true for both children with (from 33 to 37 %, r = 0.784, p < 0.001) and without (from 25 to 31 %, (r = 0.920, p < 0.001) IOL. CONCLUSIONS: An increase in IOL at term is not associated with a decline in perinatal mortality. Perinatal morbidity increased with and without induction of labor.

Nitrogen and phosphorus removal of locally adapted plant species used in constructed wetlands in China.

This paper assesses the nitrogen and phosphorus removal efficiency of seven plant species (Schoenoplectus lacustris, Vetiveria zizanioides, Acorus calamus, Canna indica, Zizania latifolia, Phragmites communis, and Iris pseudacorus) commonly used in constructed wetland systems in southern China. The investigation considers two aspects that are relevant to determine nutrient removal efficiency: plants' biomass production and nutrient content in water effluent. Both assessments are correlated with each other. Three different hydraulic retention times with different nutrient loads have been applied in this ex-situ trial. The plants' biomass production correlates positively with the effluent's nutrient removal efficiency. Six out of seven species reviewed produce more biomass above ground than below ground (average: 67% of dried biomass in aerial part); only I. pseudacorus produces more biomass below ground. S. lacustris, V. zizanioides, I. pseudacorus, and C. indica have performed best in terms of nutrient removal efficiency (65.6-90.2% for nitrogen; 67.7-84.6% for phosphorus).

Reappraising the concept of massive transfusion in trauma.

INTRODUCTION: The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols. METHODS: Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed. RESULTS: In total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%. CONCLUSIONS: No threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.

An automated high throughput solution for DNA extraction and bisulfite-conversion from high volume liquid biopsy specimens: sample preparation for epigenetic analysis.

OBJECTIVE: DNA methylation analysis via real-time PCR or other analytical techniques requires purified bisulfite converted DNA. We report on an automated high throughput solution for DNA extraction, bisulfite-conversion, and purification of 96 samples with an input volume of up to 3.5 mL of plasma or urine, using reagents from the commercially available Epi BisKit. RESULTS: Magnetic bead-based DNA extraction, bisulfite conversion at high temperature, and efficient DNA purification was conducted on a customized commercially available liquid-handling platform. A highly interlaced 4 × 24 sample protocol was implemented for DNA extraction, elution in a 96-well plate, efficient bisulfite-conversion and extensive purification. The resulting bisulfite-converted DNA was stored in a 96-well format, ready for PCR set-up or other down-stream applications. The automated method is a walk-away solution for processing 96 samples in 7 h 30 min. Performance of the method was validated by comparison with the standard manual method of the Epi BiSKit using technical and biological samples. Overall DNA yield was assessed with a standardized ß-actin assay. The automated workflow demonstrated equivalent performance to the manual method for technical, plasma and urine samples. It may provide a new standard for effective high-throughput preparation of bisulfite-converted DNA from a variety of high volume liquid biopsy specimens.

Reduction in critical mortality in urban mass casualty incidents: analysis of triage, surge, and resource use after the London bombings on July 7, 2005.

BACKGROUND: The terrorist bombings in London on July 7, 2005, produced the largest mass casualty event in the UK since World War 2. The aim of this study was to analyse the prehospital and in-hospital response to the incident and identify system processes that optimise resource use and reduce critical mortality. METHODS: This study was a retrospective analysis of the London-wide prehospital response and the in-hospital response of one academic trauma centre. Data for injuries, outcome, triage, patient flow, and resource use were obtained by the review of emergency services and hospital records. FINDINGS: There were 775 casualties and 56 deaths, 53 at scene. 55 patients were triaged to priority dispatch and 20 patients were critically injured. Critical mortality was low at 15% and not due to poor availability of resources. Over-triage rates were reduced where advanced prehospital teams did initial scene triage. The Royal London Hospital received 194 casualties, 27 arrived as seriously injured. Maximum surge rate was 18 seriously injured patients per hour and resuscitation room capacity was reached within 15 min. 17 patients needed surgery and 264 units of blood products were used in the first 15 h, close to the hospital's routine daily blood use. INTERPRETATION: Critical mortality was reduced by rapid advanced major incident management and seems unrelated to over-triage. Hospital surge capacity can be maintained by repeated effective triage and implementing a hospital-wide damage control philosophy, keeping investigations to a minimum, and transferring patients rapidly to definitive care.

Validation of the SHOX2/PTGER4 DNA Methylation Marker Panel for Plasma-Based Discrimination between Patients with Malignant and Nonmalignant Lung Disease.

INTRODUCTION: Low-dose computed tomography (LDCT) is used for screening for lung cancer (LC) in high-risk patients in the United States. The definition of high risk and the impact of frequent false-positive results of low-dose computed tomography remains a challenge. DNA methylation biomarkers are valuable noninvasive diagnostic tools for cancer detection. This study reports on the evaluation of methylation markers in plasma DNA for LC detection and discrimination of malignant from nonmalignant lung disease. METHODS: Circulating DNA was extracted from 3.5-mL plasma samples, treated with bisulfite using a commercially available kit, purified, and assayed by real-time polymerase chain reaction for assessment of DNA methylation of short stature homeobox 2 gene (SHOX2), prostaglandin E receptor 4 gene (PTGER4), and forkhead box L2 gene (FOXL2). In three independent case-control studies these assays were evaluated and optimized. The resultant assay, a triplex polymerase chain reaction combining SHOX2, PTGER4, and the reference gene actin, beta gene (ACTB), was validated using plasma from patients with and without malignant disease. RESULTS: A panel of SHOX2 and PTGER4 provided promising results in three independent case-control studies examining a total of 330 plasma specimens (area under the receiver operating characteristic curve = 91%-98%). A validation study with 172 patient samples demonstrated significant discriminatory performance in distinguishing patients with LC from subjects without malignancy (area under the curve = 0.88). At a fixed specificity of 90%, sensitivity for LC was 67%; at a fixed sensitivity of 90%, specificity was 73%. CONCLUSIONS: Measurement of SHOX2 and PTGER4 methylation in plasma DNA allowed detection of LC and differentiation of nonmalignant diseases. Development of a diagnostic test based on this panel may provide clinical utility in combination with current imaging techniques to improve LC risk stratification.

Risk of Inhospital Stroke or Death Is Associated With Age But Not Sex in Patients Treated With Carotid Endarterectomy for Asymptomatic or Symptomatic Stenosis in Routine Practice: Secondary Data Analysis of the Nationwide German Statutory Quality Assurance Database From 2009 to 2014.

BACKGROUND: Guideline recommendations on carotid endarterectomy are based predominantly on randomized, controlled trials, in which women or elderly patients are often under-represented. This study analyzed the association of age and sex with the risk of in-hospital stroke or death following carotid endarterectomy under routine conditions in Germany. METHODS AND RESULTS: Secondary data analysis using the Statutory German Quality Assurance Database on all carotid endarterectomy procedures (n=142 074) performed between 2009 and 2014. Primary outcome was any stroke or death until discharge; secondary outcomes were any in-hospital stroke (alone), and death (alone). Descriptive statistics and multilevel multivariable regression analyses were applied. Patients were predominately male (68%), with mean age 71 years. Carotid stenosis was symptomatic in 40%. Primary outcome occurred in 1.8% of women and 1.9% of men. Multivariable regression analysis revealed that more-advanced age was associated with a higher primary outcome rate (relative risk [RR] per 10-year increase: 1.19; 95% CI, 1.14-1.24). Risk of death (alone) was associated with age (RR, 1.68; 95% CI, 1.54-1.84). Age was associated with the risk of stroke (alone; RR, 1.05; 95% CI, 1.00-1.11). Sex was not associated with primary outcome rate (1.01; 95% CI, 0.93-1.10), nor did it significantly modify the age effect. CONCLUSIONS: This study shows that increasing age, but not sex, is associated with a higher risk of in-hospital stroke or death following carotid endarterectomy under everyday conditions in Germany. Whereas the risk of death (alone) is significantly associated with age, the association between age and the risk of stroke (alone) can be considered of minor importance.

Global field synchronization reveals rapid eye movement sleep as most synchronized brain state in the human EEG.

Sleep is characterized by a loss of consciousness, which has been attributed to a breakdown of functional connectivity between brain regions. Global field synchronization (GFS) can estimate functional connectivity of brain processes. GFS is a frequency-dependent measure of global synchronicity of multi-channel EEG data. Our aim was to explore and extend the hypothesis of disconnection during sleep by comparing GFS spectra of different vigilance states. The analysis was performed on eight healthy adult male subjects. EEG was recorded during a baseline night, a recovery night after 40 h of sustained wakefulness and at 3 h intervals during the 40 h of wakefulness. Compared to non-rapid eye movement (NREM) sleep, REM sleep showed larger GFS values in all frequencies except in the spindle and theta bands, where NREM sleep showed a peak in GFS. Sleep deprivation did not affect GFS spectra in REM and NREM sleep. Waking GFS values were lower compared with REM and NREM sleep except for the alpha band. Waking alpha GFS decreased following sleep deprivation in the eyes closed condition only. Our surprising finding of higher synchrony during REM sleep challenges the view of REM sleep as a desynchronized brain state and may provide insight into the function of REM sleep.

Conjunctival lymphangioma in a 4-year-old girl revealed tuberous sclerosis complex.

Background: To present a case of conjunctival lymphangioma in a 4-year-old girl with tuberous sclerosis complex. Methods/results: A 4-year-old girl presented with a relapsing cystic lesion of the bulbar conjunctiva in the right eye with string-of-pearl-like dilation of lymphatic vessels and right-sided facial swelling with mild pain. Best-corrected vision was not impaired. Examination of the skin revealed three hypomelanotic macules and a lumbal Shagreen patch. Magnetic resonance imaging (MRI) findings displayed minimal enhancement of buccal fat on the right side. Cranial and orbital MRI showed signal enhancement in the right cortical and subcortical areas. Genetic analysis revealed a heterozygous deletion encompassing exon 1 and 2 of the TSC1 gene (tuberous sclerosis complex 1 gene), confirming the diagnosis of tuberous sclerosis complex. Conclusion: In conjunctival lymphangioma, tuberous sclerosis complex should be considered as the primary disease.

Pharmacological interventions in traumatic brain injury: Can we rely on systematic reviews for evidence?

INTRODUCTION: Providing current, reliable and evidence based information for clinicians and researchers in a synthesised and summarised way can be challenging particularly in the area of traumatic brain injury where a vast number of reviews exists. These reviews vary in their methodological quality and are scattered across varying sources. In this paper, we present an overview of systematic reviews that evaluate the pharmacological interventions in traumatic brain injury (TBI). By doing this, we aim to evaluate the existing evidence for improved outcomes in TBI with pharmacological interventions, and to identify gaps in the literature to inform future research. METHODS: We searched the Neurotrauma Evidence Map on systematic reviews relating to pharmacological interventions for managing TBI in acute phase. Two reviewers independently screened search results and appraised each systematic review using the validated AMSTAR tool and extracted data from the review. RESULTS: A total of 288 systematic reviews relating to TBI were available on the Neurotrauma Evidence Map at the time of this study. We identified 19 systematic reviews on pharmacological management for acute TBI with publications dates ranging from 1998 to 2014. The studies were of varying methodological quality, with a mean AMSTAR score of 7.78 (range 2-11]. CONCLUSION: The evidence from high quality systematic reviews show that there is currently insufficient evidence for the use of magnesium, monoaminergic and dopamine agonists, progesterone, aminosteroids, excitatory amino acid inhibitors, haemostatic and antifibrinolytic drugs in TBI. Anti-convulsants are only effective in reducing early seizures with no significant difference between phenytoin and leviteracetam. There is no difference between propofol and midazolam for sedation in TBI patients and ketamine may not cause increased ICP. Overviews of systematic review provide informative and powerful summaries of evidence based research.

Significant Association of Annual Hospital Volume With the Risk of Inhospital Stroke or Death Following Carotid Endarterectomy but Likely Not After Carotid Stenting: Secondary Data Analysis of the Statutory German Carotid Quality Assurance Database.

BACKGROUND: Associations between hospital volume and the risk of stroke or death following carotid endarterectomy (CEA) and carotid artery stenting (CAS) on a national level in Germany were analyzed. METHODS AND RESULTS: Secondary data analysis using microdata from the nationwide statutory German quality assurance database on all surgical or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014. Hospitals were categorized into empirically determined quintiles according to the annual case volume. The resulting volume thresholds were 10, 25, 46, and 79 for CEA and 2, 6, 12, and 26 for CAS procedures. The primary outcome was any stroke or death before hospital discharge. For risk-adjusted analyses, a multilevel regression model was applied. The analysis included 161 448 CEA and 17 575 CAS procedures. In CEA patients, the crude risk of stroke or death decreased monotonically from 4.2% (95% confidence interval, 3.6%-4.9%) in low-volume hospitals (first quintile 1-10 CEA per year) to 2.1% (2.0%-2.2%) in hospitals providing ≥80 CEA per year (fifth quintile; P<0.001 for trend). The overall risk of any stroke or death in CAS patients was 3.7% (3.5%-4.0%), but no trend on annual volume was seen (P=0.304). Risk-adjusted analyses confirmed a significant inverse relationship between hospital volume (categorized or continuous) and the risk of stroke or death after CEA but not CAS procedures. CONCLUSIONS: An inverse volume-outcome relationship in CEA-treated patients was demonstrated. No significant association between hospital volume and the risk of stroke or death was found for CAS.

The CD23b promoter is a target for NF-AT transcription factors in B-CLL cells.

CD23 is atypically highly expressed in various chronic diseases, including B-CLL, lupus erythematodes and rheumatoid arthritis. Its expression can be further enhanced by interleukin 4 (IL-4). We have shown before that in B-CLL cells nuclear factor(s) of activated T cells (NF-ATs) show permanent nuclear localization and therefore constitutive transcriptional activity. Here we identify CD23b promoter as a novel target for NF-AT factors in B-CLL cells. The CD23b promoter contains two NF-AT binding sites to which NF-ATp and NF-ATc factors bind with high affinity. Mutations introduced into these sites abolished NF-AT binding and impaired the promoter activity, as did cyclosporin A (CsA), an inhibitor of nuclear transport of NF-ATs. Furthermore, we show that IL-4-induced transcription factor STAT6 cooperates with NF-ATs in the induction of the CD23b promoter activity. These results show that the CD23b promoter is a target for NF-AT factors and suggest that the cooperation between NF-AT and STAT factors might be one of the molecular mechanisms responsible for high-level expression of CD23 on the surface of B-CLL cells.

Case Numbers and Process Quality in Breast Surgery in Germany: A Retrospective Analysis of Over 150,000 Patients From 2013 to 2014.

BACKGROUND: Numerous studies from around the world have shown a positive association between case numbers and the quality of medical care. The evidence to date suggests that conformity to guidelines for the treatment of patients with breast cancer is better in German hospitals that have higher case numbers. METHODS: We used data obtained by an external program for quality assurance in inpatient care (externe stationäre Qualitätssicherung, esQS) for the years 2013 and 2014 to investigate seven process indicators in the area of breast surgery, including histologic confirmation of the diagnosis before definitive treatment, axillary dissection as recommended by the guidelines, and an appropriate temporal interval between diagnosis and operation. Case numbers were categorized with the aid of various threshold values. Moreover, subgroup analyses were carried out for patients under age 65, patients in good general health, patients without lymph-node involvement, and patients with a tumor size pT0 or pT1 or an overall tumor size less than 5 cm. RESULTS: Data on 153,475 patients from 939 hospitals were analyzed. Six of seven indicators had values that were better overall, to a statistically significant extent, in hospitals with higher case numbers. Although this relationship was not consistently seen, the worst results were generally found in the category with the lowest case numbers. Similar though less striking results were obtained in the subgroup analyses. An exception to the general finding was that, in hospitals with higher case numbers, the interval between diagnosis and operation was more often longer than three weeks. CONCLUSION: Guideline adherence is higher in hospitals that treat more cases. The present study does not address the question whether this, in turn, affects morbidity or mortality. To improve process quality in peripheral hospitals, the quality assurance program should be continued.