Development and validation of the tic score for early detection of traumatic coagulopathy upon hospital admission: a cohort study.

BACKGROUND: Critically injured patients need rapid and appropriate hemostatic treatment, which requires prompt identification of trauma-induced coagulopathy (TIC) upon hospital admission. We developed and validated the performance of a clinical score based on prehospital resuscitation parameters and vital signs at hospital admission for early diagnosis of TIC. METHODS: The score was derived from a level-1 trauma center registry (training set). It was then validated on data from two other level-1 trauma centers: first on a trauma registry (retrospective validation set), and then on a prospective cohort (prospective validation set). TIC was defined as a PTratio > 1.2 at hospital admission. Prehospital (vital signs and resuscitation care) and admission data (vital signs and laboratory parameters) were collected. We considered parameters independently associated with TIC in the score (binomial logistic regression). We estimated the score's performance for the prediction of TIC. RESULTS: A total of 3489 patients were included, and among these a TIC was observed in 22% (95% CI 21-24%) of cases. Five criteria were identified and included in the TIC Score: Glasgow coma scale < 9, Shock Index > 0.9, hemoglobin < 11 g.dL-1, prehospital fluid volume > 1000 ml, and prehospital use of norepinephrine (yes/no). The score, ranging from 0 and 9 points, had good performance for the identification of TIC (AUC: 0.82, 95% CI: 0.81-0.84) without differences between the three sets used. A score value < 2 had a negative predictive value of 93% and was selected to rule-out TIC. Conversely, a score value ≥ 6 had a positive predictive value of 92% and was selected to indicate TIC. CONCLUSION: The TIC Score is quick and easy to calculate and can accurately identify patients with TIC upon hospital admission.

ZeBraInspector, a platform for the automated segmentation and analysis of body and brain volumes in whole 5 days post-fertilization zebrafish following simultaneous visualization with identical orientations.

In recent years, the zebrafish has become a well-established laboratory model. We describe here the ZeBraInspector (ZBI) platform for high-content 3D imaging (HCI) of 5 days post-fertilization zebrafish eleuthero-embryos (EEs). This platform includes a mounting method based on 3D-printed stamps to create a grid of wells in an agarose cast, facilitating batch acquisitions with a fast-confocal laser scanning microscope. We describe reference labeling in cleared fish with a fluorescent lipophilic dye. Based on this labeling, the ZBI software registers. EE 3D images, making it possible to visualize numerous identically oriented EEs on a single screen, and to compare their morphologies and any fluorescent patterns at a glance. High-resolution 2D snapshots can be extracted. ZBI software is therefore useful for diverse high-content analyses (HCAs). Following automated segmentation of the lipophilic dye signal, the ZBI software performs volumetric analyses on whole EEs and their nervous system white matter. Through two examples, we illustrate the power of these analyses for obtaining statistically significant results from a small number of samples: the characterization of a phenotype associated with a neurodevelopmental mutation, and of the defects caused by treatments with a toxic anti-cancer compound.

The decoupled evolution of the organellar genomes of Silene nutans leads to distinct roles in the speciation process.

There is growing evidence that cytonuclear incompatibilities (i.e. disruption of cytonuclear coadaptation) might contribute to the speciation process. In a former study, we described the possible involvement of plastid-nuclear incompatibilities in the reproductive isolation between four lineages of Silene nutans (Caryophyllaceae). Because organellar genomes are usually cotransmitted, we assessed whether the mitochondrial genome could also be involved in the speciation process, knowing that the gynodioecious breeding system of S. nutans is expected to impact the evolutionary dynamics of this genome. Using hybrid capture and high-throughput DNA sequencing, we analyzed diversity patterns in the genic content of the organellar genomes in the four S. nutans lineages. Contrary to the plastid genome, which exhibited a large number of fixed substitutions between lineages, extensive sharing of polymorphisms between lineages was found in the mitochondrial genome. In addition, numerous recombination-like events were detected in the mitochondrial genome, loosening the linkage disequilibrium between the organellar genomes and leading to decoupled evolution. These results suggest that gynodioecy shaped mitochondrial diversity through balancing selection, maintaining ancestral polymorphism and, thus, limiting the involvement of the mitochondrial genome in evolution of hybrid inviability between S. nutans lineages.

Thromboelastometry-guided haemostatic resuscitation in severely injured patients: a propensity score-matched study.

BACKGROUND: To accelerate the diagnosis and treatment of trauma-induced coagulopathy (TIC), viscoelastic haemostatic assays (VHA) are increasingly used worldwide, although their value is still debated, with a recent randomised trial showing no improvement in outcome. The objective of this retrospective study was to compare 2 cohorts of injured patients in which TIC was managed with either a VHA-based algorithm or a conventional coagulation test (CCT)-based algorithm. METHODS: Data were retrieved from 2 registries and patients were included in the study if they received at least 1 unit of red blood cell in the first 24 h after admission. A propensity score, including sex, age, blunt vs. penetrating, systolic blood pressure, GCS, ISS and head AIS, admission lactate and PTratio, tranexamic acid administration, was then constructed. Primary outcome was the proportion of subjects who were alive and free of massive transfusion (MT) at 24 h after injury. We also compared the cost for blood products and coagulation factors. RESULTS: From 2012 to 2019, 7250 patients were admitted in the 2 trauma centres, and among these 624 were included in the study (CCT group: 380; VHA group: 244). After propensity score matching, 215 patients remained in each study group without any significant difference in demographics, vital signs, injury severity, or laboratory analysis. At 24 h, more patients were alive and free of MT in the VHA group (162 patients, 75%) as compared to the CCT group (112 patients, 52%; p < 0.01) and fewer patients received MT (32 patients, 15% vs. 91 patients, 42%, p < 0.01). However, no significant difference was observed for mortality at 24 h (odds ratio 0.94, 95% CI 0.59-1.51) or survival at day 28 (odds ratio 0.87, 95% CI 0.58-1.29). Overall cost of blood products and coagulation factors was dramatically reduced in the VHA group as compared to the CCT group (median [interquartile range]: 2357 euros [1108-5020] vs. 4092 euros [2510-5916], p < 0.001). CONCLUSIONS: A VHA-based strategy was associated with an increase of the number of patients alive and free of MT at 24 h together with an important reduction of blood product use and associated costs. However, that did not translate into an improvement in mortality.

Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial.

BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.

Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Estimating the time structure of descending activation that generates movements at different speeds.

In targeted movements of the hand, descending activation patterns must not only generate muscle activation but also adjust spinal reflexes from stabilizing the initial to stabilizing the final postural state. We estimate descending activation patterns that change minimally while generating a targeted movement within a given movement time based on a model of the biomechanics, the muscle dynamics, and the stretch reflex. The estimated descending activation patterns predict human movement trajectories quite well. Their temporal structure varies across workspace and with movement speed, from monotonic profiles for slow movements to nonmonotonic profiles for fast movements. Descending activation patterns at different speeds thus do not result from a mere rescaling of invariant templates but reflect varying needs to compensate for interaction torques and muscle dynamics. The virtual attractor trajectories, on which active muscle torques are zero, lie within reachable workspace and are largely invariant when represented in end-effector coordinates. Their temporal structure along movement direction changes from linear ramps to "N-shaped" profiles with increasing movement speed.NEW & NOTEWORTHY The descending activation patterns driving movement must be integrated with spinal reflexes, which would resist movement if left unchanged. We estimate the descending activation patterns at different movement speeds using a model of the stretch reflex and of muscle and limb dynamics. The descending activation patterns we find are temporally structured to compensate for interaction torques as predicted by internal models but also shift the reflex threshold, solving the posture-movement problem.

Reproductive isolation among lineages of Silene nutans (Caryophyllaceae): A potential involvement of plastid-nuclear incompatibilities.

Early stages of speciation in plants might involve genetic incompatibilities between plastid and nuclear genomes, leading to inter-lineage hybrid breakdown due to the disruption between co-adapted plastid and nuclear genes encoding subunits of the same plastid protein complexes. We tested this hypothesis in Silene nutans, a gynodioecious Caryophyllaceae, where four distinct genetic lineages exhibited strong reproductive isolation among each other, resulting in chlorotic or variegated hybrids. By sequencing the whole gene content of the four plastomes through gene capture, and a large part of the nuclear genes encoding plastid subunits from RNAseq data, we searched for non-synonymous substitutions fixed in each lineage on both genomes. Lineages of S. nutans exhibited a high level of dN/dS ratios for plastid and nuclear genes encoding most plastid complexes, with a strong pattern of coevolution for genes encoding the subunits of ribosome and cytochrome b6/f that could explain the chlorosis of hybrids. Overall, relaxation of selection due to past bottlenecks and positive selection have driven the diversity pattern observed in S. nutans plastid complexes, leading to plastid-nuclear incompatibilities. We discuss the possible role of gynodioecy in the evolutionary dynamics of the plastomes through linked selection.

Prehospital Tranexamic Acid in Major Pediatric Trauma Within a Physician-Led Emergency Medical Services System: A Multicenter Retrospective Study.

OBJECTIVES: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use. DESIGN: Multicenter, retrospective study, 2014-2020. SETTING: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system. PATIENTS: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9-16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13-17] vs 12 yr [6-16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9-25] vs 6 [2-13]; p < 0.001). The median dosage was 16 mg/kg (13-19 mg/kg). TXA administration was found in 51.8% cases ( n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients ( n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1-12.3 and OR, 4.5; 95% CI, 2.9-6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1-1.3) were associated with prehospital TXA administration. CONCLUSIONS: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription.

yacrd and fpa: upstream tools for long-read genome assembly.

MOTIVATION: Genome assembly is increasingly performed on long, uncorrected reads. Assembly quality may be degraded due to unfiltered chimeric reads; also, the storage of all read overlaps can take up to terabytes of disk space. RESULTS: We introduce two tools: yacrd for chimera removal and read scrubbing, and fpa for filtering out spurious overlaps. We show that yacrd results in higher-quality assemblies and is one hundred times faster than the best available alternative. AVAILABILITY AND IMPLEMENTATION: https://github.com/natir/yacrd and https://github.com/natir/fpa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Outcome of publicly funded nationwide first-tier noninvasive prenatal screening.

PURPOSE: Noninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal care. Belgium was the first country to implement and fully reimburse NIPS as a first-tier screening test offered to all pregnant women. A consortium consisting of all Belgian genetic centers report the outcome of two years genome-wide NIPS implementation. METHODS: The performance for the common trisomies and for secondary findings was evaluated based on 153,575 genome-wide NIP tests. Furthermore, the evolution of the number of invasive tests and the incidence of Down syndrome live births was registered. RESULTS: Trisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) of 92.4%, 84.6%, and 43.9%. Rare autosomal trisomies and fetal segmental imbalances were detected in respectively 0.23% and 0.07% of cases with PPVs of 4.1% and 47%. The number of invasive obstetric procedures decreased by 52%. The number of trisomy 21 live births dropped to 0.04%. CONCLUSION: Expanding the scope of NIPS beyond trisomy 21 fetal screening allows the implementation of personalized genomic medicine for the obstetric population. This genome-wide NIPS approach has been embedded successfully in prenatal genetic care in Belgium and might serve as a framework for other countries offering NIPS.

Association Between Short-, Intermediate-, and Long-term Mortality and Myocardial Injury After Noncardiac Surgery After Hip Fracture Surgery: A Retrospective Cohort.

BACKGROUND: For more than 20 years, hip fracture 1-year mortality has remained around 20%. An elevation of the postoperative troponin peak within 72 hours (myocardial injury after noncardiac surgery [MINS]) is associated with a greater risk of short-term mortality in the general population. However, there seem to be conflicting results in the specific population who undergo hip fracture surgery, with some studies finding an association between troponin and mortality and some not. The objective of the present study was to investigate the association of MINS and the short- (before 28th day), intermediate- (before 180th day), and long-term (before 365th day) mortality after hip fracture surgery. METHODS: We conducted a single-center retrospective cohort of patients undergoing hip fracture surgery from November 2013 to December 2015. MINS was defined as postoperative troponin peak within the 72 hours >5 ng/L. Four MINS subgroups were defined according to the value of troponin peak (ie, ≥5-<20, ≥20-<65, ≥65-<1000, and ≥1000 ng/L). To document the association between the different mortality terms and the troponin peak, odds ratio (OR) and adjusted OR (aOR) associated with their 95% confidence interval (CI) with the log of the scaled troponin peak within 72 hours were estimated, with and without patients presenting a postoperative acute coronary syndrome (ACS). Cox proportional hazards modeling was used to estimate hazard ratio (HR) and adjusted HR (aHR) of death between the no MINS and MINS subgroups. The adjustment was performed on the main confounding factors (ie, sex, American Society of Anesthesiologists [ASA] physical status, dementia status, age, and time from admission to surgery). RESULTS: Among 729 participants, the mean age was 83.1 (standard deviation [SD] = 10.8) years, and 77.4% were women; 30 patients presented an ACS (4%). Short-, intermediate-, and long-term mortality were at 5%, 16%, and 23%, respectively. The troponin peak was significantly associated with all terms of mortality before and after adjustment and before and after exclusion of patients presenting an ACS. HR and aHR for each subgroup of troponin level were significantly associated with an increased probability of survival, except for the 5 to 20 ng/L group for which aHR was not significant (1.75, 95% CI, 0.82-3.74). In the landmark analysis, there was still an association between survival at the 365th day and troponin peak after the short- and intermediate-term truncated mortality. CONCLUSIONS: MINS is associated with short-, intermediate-, and long-term mortality after hip fracture surgery. This could be a valuable indicator to determine the population at high risk of mortality that could benefit from targeted prevention and possible intervention.

Safety and efficacy of a strategy of vitamin K antagonist reversal with prothrombin complex concentrates compared to vitamin K in patients with hip fracture.

Background: Increased preoperative delay in patients with hip fractures may be responsible for increased morbidity and mortality. We hypothesized that a strategy of reversal of vitamin K antagonist (VKA) by prothrombin complexes concentrates (PCCs), as compared to vitamin K, is safe and reduces preoperative delay and hospital length of stay (LOS). Methods: In this pilot study, we reviewed the records of patients admitted to a university-affiliated hospital for hip fracture between Jan. 1, 2012, and Dec. 31, 2016, who were taking VKA. Patients were stratified according to reversal strategy (vitamin K v. PCC). Adverse effects, time to surgery, LOS and mortality were collected from the electronic medical record and were compared between the 2 study groups and a control group not treated with VKA. Results: A total of 141 patients were included in the study: 65 in the vitamin K group, 26 in the PCC group and 50 in the control group. The median preoperative delay in the PCC group (20 h [interquartile range (IQR)] 13-25 h]) and the control group (20 h [IQR 15-33 h]) was lower than that in the vitamin K group (45 h [IQR 31-52 h]) (p < 0.001). Patients in the PCC group had a shorter median hospital LOS than those in the vitamin K group (6 d [IQR 4-9 d] v. 8 d [IQR 6-11 d], p < 0.05). No difference was observed in the proportion of patients who received a red blood cell transfusion, or had thrombotic or hemorrhagic complications. No difference in mortality at 12 months was observed between the groups. Conclusion: In patients with hip fracture, the use of PCCs as compared to vitamin K to reverse the effect of VKA significantly reduced preoperative delay and hospital LOS, and was not associated with an increase in the rates of thrombotic or hemorrhagic complications. Prospective studies involving a greater number of patients are required to confirm these promising results.

Contexte: L'allongement du délai préopératoire chez les patients atteints d'une fracture de la hanche pourrait expliquer l'augmentation de la morbidité et de la mortalité. Selon notre hypothèse, une stratégie d'inversion des antagonistes de la vitamine K (AVK) au moyen de concentrés de complexes prothrombiques (CCP), plutôt que de vitamine K, est sécuritaire et réduit le délai préopératoire et la durée du séjour hospitalier. Méthodes: Pendant cette étude pilote, nous avons passé en revue les dossiers de patients sous AVK admis dans un centre universitaire pour fracture de la hanche entre le 1er janvier 2012 et le 31 décembre 2016. Les patients ont été stratifiés selon la stratégie d'inversion choisie (vitamine K c. CCP). Les effets indésirables, le délai préopératoire, la durée du séjour hospitalier et la mortalité ont été recueillis à partir des dossiers médicaux électroniques et ont été comparés entre les 2 groupes de l'étude et un groupe témoin non sous AVK. Résultats: En tout, 141 patients ont été inclus dans l'étude, 65 dans le groupe sous vitamine K, 26 dans le groupe sous CCP et 50 dans le groupe témoin. Le délai préopératoire médian pour le groupe sous CCP (20 h [éventail interquartile (ÉIQ)] 13­25 h]) et le groupe témoin (20 h [ÉIQ 15­33 h]) a été plus bref que pour le groupe sous vitamine K (45 h [ÉIQ 31­52 h]) (p < 0,001). Les patients du groupe sous CCP ont eu un séjour hospitalier médian plus bref que les patients du groupe sous vitamine K (6 j [ÉIQ 4­9 j] c. 8 j [ÉIQ 6­11 j]) (p < 0,05). Aucune différence n'a été observée quant à la proportion de patients ayant reçu une transfusion de culot globulaire ou ayant manifesté des complications thrombotiques ou hémorragiques. Aucune différence quant à la mortalité à 12 mois n'a été observée entre les groupes. Conclusion: Chez les patients atteints d'une fracture de la hanche, l'utilisation des CCP plutôt que de la vitamine K pour inverser l'effet des AVK a significativement abrégé le délai préopératoire et la durée du séjour hospitalier, et n'a pas été associée à une augmentation des taux de complications thrombotiques ou hémorragiques. Des études prospectives sur un plus grand nombre de patients sont nécessaires pour confirmer ces résultats prometteurs.

Genome-Wide Identification, Structure Characterization, and Expression Pattern Profiling of the Aquaporin Gene Family in Betula pendula.

Aquaporin water channels (AQPs) constitute a large family of transmembrane proteins present throughout all kingdoms of life. They play key roles in the flux of water and many solutes across the membranes. The AQP diversity, protein features, and biological functions of silver birch are still unknown. A genome analysis of Betula pendula identified 33 putative genes encoding full-length AQP sequences (BpeAQPs). They are grouped into five subfamilies, representing ten plasma membrane intrinsic proteins (PIPs), eight tonoplast intrinsic proteins (TIPs), eight NOD26-like intrinsic proteins (NIPs), four X intrinsic proteins (XIPs), and three small basic intrinsic proteins (SIPs). The BpeAQP gene structure is conserved within each subfamily, with exon numbers ranging from one to five. The predictions of the aromatic/arginine selectivity filter (ar/R), Froger's positions, specificity-determining positions, and 2D and 3D biochemical properties indicate noticeable transport specificities to various non-aqueous substrates between members and/or subfamilies. Nevertheless, overall, the BpePIPs display mostly hydrophilic ar/R selective filter and lining-pore residues, whereas the BpeTIP, BpeNIP, BpeSIP, and BpeXIP subfamilies mostly contain hydrophobic permeation signatures. Transcriptional expression analyses indicate that 23 BpeAQP genes are transcribed, including five organ-related expressions. Surprisingly, no significant transcriptional expression is monitored in leaves in response to cold stress (6 °C), although interesting trends can be distinguished and will be discussed, notably in relation to the plasticity of this pioneer species, B. pendula. The current study presents the first detailed genome-wide analysis of the AQP gene family in a Betulaceae species, and our results lay a foundation for a better understanding of the specific functions of the BpeAQP genes in the responses of the silver birch trees to cold stress.

Graph analysis of fragmented long-read bacterial genome assemblies.

MOTIVATION: Long-read genome assembly tools are expected to reconstruct bacterial genomes nearly perfectly; however, they still produce fragmented assemblies in some cases. It would be beneficial to understand whether these cases are intrinsically impossible to resolve, or if assemblers are at fault, implying that genomes could be refined or even finished with little to no additional experimental cost. RESULTS: We propose a set of computational techniques to assist inspection of fragmented bacterial genome assemblies, through careful analysis of assembly graphs. By finding paths of overlapping raw reads between pairs of contigs, we recover potential short-range connections between contigs that were lost during the assembly process. We show that our procedure recovers 45% of missing contig adjacencies in fragmented Canu assemblies, on samples from the NCTC bacterial sequencing project. We also observe that a simple procedure based on enumerating weighted Hamiltonian cycles can suggest likely contig orderings. In our tests, the correct contig order is ranked first in half of the cases and within the top-three predictions in nearly all evaluated cases, providing a direction for finishing fragmented long-read assemblies. AVAILABILITY AND IMPLEMENTATION: https://gitlab.inria.fr/pmarijon/knot . SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hydrogen peroxide generated by over-expression of cytosolic superoxide dismutase in transgenic plums enhances bacterial canker resistance and modulates plant defence responses.

H2O2 generated during the oxidative burst, plays important roles in plant defenses responses against pathogens. In this study we examined the role of H2O2 on bacterial canker resistance in transgenic plums over-expressing cytosolic superoxide dismutase. Three transgenic lines (C64, C66 and F12) with elevated levels of H2O2 accumulation showed enhanced resistance against bacterial canker disease caused by Pseudomonas syringae pv. syringae, when compared to the non-transformed control. Analysis of the expression of several genes involved in the plant-pathogen interaction showed that the expression of those involved in SA pathway (pr1 and npr1) and JA (lox3) were activated earlier and transiently in transgenic lines C66 and F12 when compared to the wild type. However, the expression of genes involved in anthocyanin synthesis (chi, chs, f3h, dfr, atcs, myb10) and ethylene (acs) was induced at very low levels whereas it was activated by the pathogen at exaggerated levels in the non-transformed line. These results suggest that resistance observed in transgenic lines over-producing H2O2 is correlated with an early and transient induction of defense genes associated with the SA and JA pathways and inhibition of gene expression associated with ethylene and anthocyanin biosynthesis.

Prenatally detected copy number variants in a national cohort: A postnatal follow-up study.

OBJECTIVE: Belgian genetic centers established a database containing data on all chromosomal microarrays performed in a prenatal context. A study was initiated to evaluate postnatal development in children diagnosed prenatally with a non-benign copy number variant (CNV). METHODS: All children diagnosed with a prenatally detected non-benign CNV in a Belgian genetic center between May 2013 and February 2015 were included in the patient population. The control population consisted of children who had undergone an invasive procedure during pregnancy, with no or only benign CNVs. Child development was evaluated at 36 months using three (3) questionnaires: Ages and Stages Questionnaire Third edition, Ages and Stages Questionnaire Social-Emotional Second Edition and a general questionnaire. RESULTS: A significant difference in communication and personal-social development was detected between children with a reported susceptibility CNV and both children with an unreported susceptibility CNV and the control population. The outcome of children with a particular CNV is discussed in a case-by-case manner. CONCLUSION: Our postnatal follow-up project of children with a prenatally detected non-benign CNV is the first nationwide project of its kind. A higher number of cases for each CNV category is however needed to confirm our findings.

Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality: A retrospective analysis.

BACKGROUND: Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption. OBJECTIVES: Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration. DESIGN: This was a retrospective analysis of prospectively acquired data from a trauma registry. SETTING: An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016. PATIENTS: We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%. MAIN OUTCOME MEASURE: Mortality at 24 h and at hospital discharge. RESULTS: During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2). CONCLUSION: The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.

Genome Wild Analysis and Molecular Understanding of the Aquaporin Diversity in Olive Trees (Olea Europaea L.).

Cellular aquaporin water channels (AQPs) constitute a large family of transmembrane proteins present throughout all kingdoms of life, playing important roles in the uptake of water and many solutes across the membranes. In olive trees, AQP diversity, protein features and their biological functions are still largely unknown. This study focuses on the structure and functional and evolution diversity of AQP subfamilies in two olive trees, the wild species Olea europaea var. sylvestris (OeuAQPs) and the domesticated species Olea europaea cv. Picual (OleurAQPs), and describes their involvement in different physiological processes of early plantlet development and in biotic and abiotic stress tolerance in the domesticated species. A scan of genomes from the wild and domesticated olive species revealed the presence of 52 and 79 genes encoding full-length AQP sequences, respectively. Cross-genera phylogenetic analysis with orthologous clustered OleaAQPs into five established subfamilies: PIP, TIP, NIP, SIP, and XIP. Subsequently, gene structures, protein motifs, substrate specificities and cellular localizations of the full length OleaAQPs were predicted. Functional prediction based on the NPA motif, ar/R selectivity filter, Froger's and specificity-determining positions suggested differences in substrate specificities of Olea AQPs. Expression analysis of the OleurAQP genes indicates that some genes are tissue-specific, whereas few others show differential expressions at different developmental stages and in response to various biotic and abiotic stresses. The current study presents the first detailed genome-wide analysis of the AQP gene family in olive trees and it provides valuable information for further functional analysis to infer the role of AQP in the adaptation of olive trees in diverse environmental conditions in order to help the genetic improvement of domesticated olive trees.