An interplay between a hydrogen atmosphere and dislocation characteristics in BCC Fe from time-averaged molecular dynamics.

The interplay between hydrogen and dislocations (e.g., core and elastic energies, and dislocation-dislocation interactions) has implications on hydrogen embrittlement but is poorly understood. Continuum models of hydrogen enhanced local plasticity have not considered the effect of hydrogen on dislocation core energies. Energy minimization atomistic simulations can only resolve dislocation core energies in hydrogen-free systems because hydrogen motion is omitted so hydrogen atmosphere formation can't occur. Additionally, previous studies focused more on face-centered-cubic than body-centered-cubic metals. Discrete dislocation dynamics studies of hydrogen-dislocation interactions assume isotropic elasticity, but the validity of this assumption isn't understood. We perform time-averaged molecular dynamics simulations to study the effect of hydrogen on dislocation energies in body-centered-cubic iron for several dislocation character angles. We see atmosphere formation and highly converged dislocation energies. We find that hydrogen reduces dislocation core energies but can increase or decrease elastic energies of isolated dislocations and dislocation-dislocation interaction energies depending on character angle. We also find that isotropic elasticity can be well fitted to dislocation energies obtained from simulations if the isotropic elastic constants are not constrained to their anisotropic counterparts. These results are relevant to ongoing efforts in understanding hydrogen embrittlement and provide a foundation for future work in this field.

Cognitive Digital Biomarkers from Automated Transcription of Spoken Language.

BACKGROUND: Although patients with Alzheimer's disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status. OBJECTIVE: To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing. DESIGN: Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses. SETTING: Observational cohort study. PARTICIPANTS: 146 participants in the Framingham Heart Study. MEASUREMENTS: Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions. RESULTS: Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90. CONCLUSIONS: The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.

Synthetic biology as driver for the biologization of materials sciences.

Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field.

Estimated salt intake and risk of atrial fibrillation in a prospective community-based cohort.

INTRODUCTION: Hypertension predisposes to atrial fibrillation (AF) - a major risk factor for ischaemic stroke. Since a high dietary salt consumption is associated with hypertension, we investigated the association between urinary sodium excretion as a marker for dietary sodium intake and risk of new-onset AF in community-dwelling adults. METHOD: The UK Biobank includes 40- to 69-year-old British residents recruited 2006-2010. Participants were divided into sex-specific quintiles according to 24-hour sodium excretion estimated based on spot samples with the Kawasaki equation. We excluded participants with AF at baseline. Cox regression adjusted for cardiovascular risk factors was used to assess associations with risk of AF, using the third quintile as reference. RESULTS: A total of 257 545 women and 215 535 men were included. During up to 10 years' follow-up, 2221 women and 3751 men were diagnosed with AF. There was a tendency for an increased risk of AF in the lowest and highest quintiles of estimated daily salt intake in both women and men. In the fully adjusted model, significant associations were seen amongst men in the lowest and highest quintiles of sodium excretion (hazard ratio, HRQv1 , 1.20; 95% CI, 1.08-1.32, P < 0.001, and HRQv5 1.15, 95% CI, 1.03-1.27, P = 0.011). CONCLUSION: We found evidence for a U-shaped association between estimated daily salt intake and AF risk amongst men. A suggestive J-shaped association in women was not statistically confirmed, but analyses were likely underpowered. Our results suggest that above a certain physiological minimum level progressively higher salt intake is associated with increasing risk of AF.

Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes.

We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p < 0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p = 0.00002] and the replication cohort [95% CI (0.12, 0.39) p = 0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men.Trial registration: ClinicalTrials.gov identifier NCT01049737.

History-driven population structure and asymmetric gene flow in a recovering large carnivore at the rear-edge of its European range.

Understanding the mechanisms and patterns involved in population recoveries is challenging and important in shaping conservation strategies. We used a recovering rear-edge population of brown bears at their southernmost European range in Greece as a case study (2007-2010) to explore the recovery genetics at a species' distribution edge. We used 17 microsatellite and a mitochondrial markers to evaluate genetic structure, estimate effective population size and genetic diversity, and infer gene flow between the identified subpopulations. To understand the larger picture, we also compared the observed genetic diversity of each subpopulation with other brown bear populations in the region. The results indicate that the levels of genetic diversity for bears in western Greece are the lowest recorded in southeastern Europe, but still higher than those of other genetically depauperate bear populations. Apart from a complete separation of bear populations in eastern and western Greece, our results also indicate a considerable genetic sub-structuring in the West. As bear populations in Greece are now recovering, this structure is dissolving through a "recovery cascade" of asymmetric gene flow from South to North between neighboring subpopulations, mediated mainly by males. Our study outlines the importance of small, persisting populations, which can act as "stepping stones" that enable a rapid population expansion and recovery. This in turn makes their importance much greater than their numeric or genetic contribution to a species as a whole.

De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females.

Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, X­linked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of loss­of­function KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using whole­exome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of X­linked dominant ID, and broadens the phenotype for KIAA2022 mutations.

[Obstetric outcomes after uterine compression suture for treatment of postpartum hemorrhage: Long-term monitoring of 40 cases]. / Devenir obstétrical après plicatures utérines dans le traitement de l'hémorragie de la délivrance : suivi à long terme de 40 cas.

OBJECTIVE: Uterine atony is the first cause of postpartum hemorrhage. In caesarean section, different techniques of uterine compression suture exist when uterotonic drugs fail. Their effectiveness is shown but little data on their effects on subsequent pregnancies are available. The aim of this work is analyze of the obstetrical long-term consequences after uterine compression suture. PATIENTS AND METHODS: This is a retrospective study of 40 cases of uterine compression suture performed in a level III maternity, between 2004 and 2010. The main objective is the evaluation of the obstetrical prognosis of subsequent pregnancies. The efficacy and safety of surgical techniques, according to their transfixing character or not, were analyzed. RESULTS: Eleven pregnancies after uterine compression suture were reported among 14 women whishing another pregnancy. The median time to be pregnant was 27 months (6-78 months). Nine pregnancies were conducted at term. One case of intrauterine growth restriction and a moderate prematurity at 32 weeks were observed. There was no significant difference in efficacy and early surgical complications according to the surgical technique; however, both infectious and ischemic complications were observed after transfixing compression suture. CONCLUSION: The obstetric prognosis after a uterine compression suture is kept. The transfixing techniques may cause more infectious and ischemic complications. An evaluation of surgical techniques depending on their transfixing, or not, character on a large cohort is necessary for the evaluation of the influence of the technique on fertility and postoperative complications.

[Unusual antenatal gestational choriocarcinoma]. / Présentation anténatale atypique d'un choriocarcinome gestationnel.

Choriocarcinoma is a rare and aggressive tumor that occurs mainly after a molar pregnancy, and exceptionally during a diploid viable pregnancy. We report a case of a 30 years old primipare that revealed a choriocarcinoma at 37 weeks by a generalized seizure. This unusual event did not, however, delay the early introduction of chemotherapy even in the absence of histological diagnosis. This diagnosis must be evoked in woman with genital activity presenting an unknown tumor. Treatment can be started without waiting for the histological evidence, due to the important feature of the hCG assay, significantly improving the prognosis.

Pediatric tonsillectomy: clinical practice guidelines.

OBJECTIVE: This article presents the Clinical Practice Guidelines for Pediatric Tonsillectomy of the French Society of ENT and Head and Neck Surgery (SFORL), entitled "Amygdalectomie de l'enfant : Recommandation pour la pratique clinique" (SFORL, 2009). METHOD: The French Society of ENT (SFORL), in partnership with the French Association for Ambulatory Surgery (AFCA) and French Society for Anaesthesia and Intensive Care (SFAR), set up a representative panel in the fields of anesthesiology, ENT and head-and-neck surgery, pediatrics, sleep medicine and general medicine. Following the literature analysis reported in the Presentation of the Guidelines, recommendations were drawn up taking account of risk/benefit ratios, levels of evidence, feasibility in pediatric tonsillectomy and baseline risk assessment in the relevant population. RESULTS: Around 50,000 pediatric tonsillectomies, with or without associated adenoidectomy, are performed in France each year. Postoperative morbidity and mortality are non-negligible, despite progress in peri-operative management. The present guidelines address the following questions: 1) What are the indications for tonsillectomy, notably in case of obstructive sleep disorder; 2) What pre-operative assessment is required? 3) What are the technical principles involved? 4) What are the selection criteria for ambulatory tonsillectomy? 5) How should postoperative follow-up be organized? 6) How should complications be managed? CONCLUSION: The present Clinical Practice Guidelines for pediatric tonsillectomy in France should improve clinical and organizational practices to enhance patient safety. They seek to ensure optimal conditions of care for all children undergoing tonsillectomy.

Achieving elongated lesions employing cardiac cryoablation: a preclinical evaluation study.

Cardiac cryoablation applied for treating cardiac arrhythmias has shown promising results after intervention, particularly for the creation of elongated lesions. A model for simulating and assessing cryoablation interventions was developed, evaluated and validated with animal experiments. We employed two simulations of different freezing outlet settings for a loop shaped cryocatheter, applying Pennes heat equation for cardiac tissue. Our experiments demonstrated that an equidistantly spaced freezing outlet distribution of 5mm led to an improved formation of lesions, i.e., elongated lesions were observed throughout the transmural cardiac volume and on the epicardial structure. A complete transmural frozen lesion was not achieved with a freezing outlet distance of 10mm. These simulation results could be experimentally verified by morphological and histological examinations. Using our simulation model we were able to optimize the intervention procedure by predicting and assessing the freezing process. This should further increase the success rate of cardiac cryoablation in clinical interventions.

Prediction of countershock success in patients using the autoregressive spectral estimation.

OBJECTIVES: Ventricular fibrillation (VF) is a life-threatening cardiac arrhythmia and within of minutes of its occurrence, optimal timing of countershock therapy is highly warranted to improve the chance of survival. This study was designed to investigate whether the autoregressive (AR) estimation technique was capable to reliably predict countershock success in VF cardiac arrest patients. METHODS: ECG data of 1077 countershocks applied to 197 cardiac arrest patients with out-of-hospital and in-hospital cardiac arrest between March 2002 and July 2004 were retrospectively analyzed. The ECG from the 2.5 s interval of the precountershock VF ECG was used for computing the AR based features Spectral Pole Power (SPP) and Spectral Pole Power with Dominant Frequency weighing (SPPDF) and Centroid Frequency (CF) and Amplitude Spectrum Area (AMSA) based on Fast Fourier Transformation (FFT). RESULTS: With ROC AUC values up to 84.1% and diagnostic odds ratio up to 19.12 AR based features SPP and SPPDF have better prediction power than the FFT based features CF (80.5%; 6.56) and AMSA (82.1%; 8.79). CONCLUSIONS: AR estimation based features are promising alternatives to FFT based features for countershock outcome when analyzing human data.

Localizing the accessory pathway in ventricular preexcitation patients using a score based algorithm.

OBJECTIVES: Clinical data was analyzed to find an efficient way to localize the accessory pathway in patients with ventricular preexcitation. METHODS: The delta wave morphologies and ablation sites of 186 patients who underwent catheter ablation were analyzed and an algorithm ("locAP") to localize the accessory pathway was developed from the 84 data sets with a PQ interval ≤0.12s and a QRS width ≥0.12s. Fifty additional patients were included for a prospective validation. The locAP algorithm ranks 13 locations according to the likelihood that the accessory pathway is localized there. The algorithm is based on the locAP score which uses the standardized residuals of the available data sets. RESULTS: The locAP algorithm's accuracy is 0.54 for 13 locations, with a sensitivity of 0.84, a specificity of 0.97, and a positive likelihood ratio of 24.94. If the two most likely locations are regarded, the accuracy rises to 0.79, for the three most likely locations combined the accuracy is 0.82. This new algorithm performs better than Milstein's, Fitzpatrick's, and Arruda's algorithm both in the original study population as well as in a prospective study. CONCLUSIONS: The locAP algorithm is a valid and valuable tool for clinical practice in a cardiac electrophysiology laboratory. It could be shown that use of the locAP algorithm is favorable over the localizing algorithms that are in clinical use today.

Outpatient tonsillectomy in children: a 7-year experience.

OBJECTIVES: To report our centre's experience of outpatient tonsillectomy in children over a 7-year period and to evaluate the postoperative complication rate in this type of procedure compared to tonsillectomy performed in the context of conventional hospitalisation. MATERIAL AND METHODS: Retrospective review of medical charts. RESULTS: From May 2002 to April 2009, 276 tonsillectomies were performed on an outpatient basis, i.e. 55.4% of all paediatric tonsillectomies, in children with a mean age of 5.28 years. Ninety-six children (34.8%) presented clinical OSAS. Development of an early postoperative complication (before H8) required conventional hospitalisation on D0 in six (2.1%) of these 276 children operated on an outpatient basis: early postoperative bleeding in four cases (1.4%), which required reoperation to control bleeding in three cases, refusal to feed in one case (0.3%), and a parental problem in one case (0.3%). Postoperative complications occurring after H8 required readmission in six cases (2.1%): pain and feeding difficulties in two cases (0.7%) on D1 and D5, respectively, bleeding in four cases (1.4%) with reoperation before H24 for one patient, D5 for two patients and D7 for one patient. Only one case of bleeding occurred between H8 and H24. No perioperative respiratory complications were observed in children with clinical OSAS. CONCLUSION: The results of this study show that, in line with international publications and meta-analyses, post-tonsillectomy complications between H8 and H24 postoperatively, mainly bleeding, are exceptional. Respiratory complications usually occur in high-risk clinical settings that are not eligible for outpatient surgery. Outpatient tonsillectomy is therefore a safe procedure in children presenting all of the required medical, social and organizational conditions.

[A priori prediction of gentamicin peak concentrations: Use of a simple and practical tool]. / Prédiction a priori des concentrations en gentamicine au pic : utilisation d'un outil simple et pratique.

Aminoglycosides are concentration-dependent killing antibiotics, so that it is necessary to obtain elevated peak levels to reach the pharmacokinetic-pharmacodynamic objectives. Because of their nephrotoxicity, this class of antibiotics are frequently underprescribed and giving at an insufficient dosage when prescribed. That is why therapeutical drug monitoring (TDM) of aminoglycosides is recommanded to assess efficacy. Unfortunately, this TDM allows not a dosage adaptation on the first dose of aminoglycosides. The aim of the work was to elaborate a model using simple pharmacokinetics formulae to estimate gentamicin peak levels and so to propose an optimal a priori dosage on the first dose of gentamicin. The final model was tested out on 24 patients treated by gentamicin. The model was able to predict gentamicin peak levels in 62% of patients with a 10% precision and in 79% of patients with a 15% precision. Using this simple and practical tool might avoid under-dosage of gentamicin and clinical failure due to the selection of resistant bacteriae.

Beta-1,3-glucanase from Delftia tsuruhatensis strain MV01 and its potential application in vinification.

During vinification microbial activities can spoil wine quality. As the wine-related lactic acid bacterium Pediococcus parvulus is able to produce slimes consisting of a ß-1,3-glucan, must and wine filtration can be difficult or impossible. In addition, the metabolic activities of several wild-type yeasts can also negatively affect wine quality. Therefore, there is a need for measures to degrade the exopolysaccharide from Pediococcus parvulus and to inhibit the growth of certain yeasts. We examined an extracellular ß-1,3-glucanase from Delftia tsuruhatensis strain MV01 with regard to its ability to hydrolyze both polymers, the ß-1,3-glucan from Pediococcus and that from yeast cell walls. The 29-kDa glycolytic enzyme was purified to homogeneity. It exhibited an optimal activity at 50°C and pH 4.0. The sequencing of the N terminus revealed significant similarities to ß-1,3-glucanases from different bacteria. In addition, the investigations indicated that this hydrolytic enzyme is still active under wine-relevant parameters such as elevated ethanol, sulfite, and phenol concentrations as well as at low pH values. Therefore, the characterized enzyme seems to be a useful tool to prevent slime production and undesirable yeast growth during vinification.

A two-layer gold surface with improved surface enhancement for spectro-electrochemistry using surface-enhanced infrared absorption spectroscopy.

A two-layer gold surface is developed for use with surface-enhanced infrared absorption spectroscopy (SEIRAS) consisting of a conducting underlayer onto which Au nanoparticles (AuNPs) are grown by self-catalyzed electroless deposition. AuNPs are grown on protruding substructures of the 25 nm thin underlayer. The enhancement factor of the two-layer gold surface is controlled by the growth conditions. Cytochrome c adsorbed to a self-assembled monolayer of mercaptoethanol is used as a reference system. Under optimum conditions the absorbance of the amide I band is increased by a factor of 5 versus the classical SEIRAS surface. Reversible reduction/oxidation of cytochrome c on the two-layer gold surface is shown to take place by cyclic voltammetry.

Introgression as a likely cause of mtDNA paraphyly in two allopatric skippers (Lepidoptera: Hesperiidae).

Gene transfer between species during interspecific hybridization is a widely accepted reality in plants but is considered a relatively rare phenomenon among animals. Here we describe a unique case of mitochondrial DNA (mtDNA) paraphyly in the skipper genus, Erynnis, that involves well-diverged allopatric species. Using molecular evidence from both mitochondrial and nuclear genomes, we found high levels of intraspecific divergence in the mitochondrial genome within E. propertius (over 4% pair-wise sequence divergence) but no such differentiation in the nuclear genome. Sequence comparisons with related Erynnis suggest that past, but recent and infrequent introgression between E. propertius and E. horatius is the most reasonable explanation for the observed pattern of mtDNA paraphyly. This example of putative introgression highlights the complexity of mtDNA evolution and suggests that similar processes could be operating in other taxa that have not been extensively sampled. Our observations reinforce the importance of involving multiple genes with different modes of inheritance in the analysis of population history of congeneric taxa.

Reactive diffusion under Laplace tension.

Nanostructures such as nanospheres or nanowires may contain surfaces and interfaces of pronounced curvature. To investigate the impact of severe curvature on the kinetic of reactions, thin-film Al/Cu/Al and Cu/Al/Cu triple layers are deposited on tungsten tips of 25nm curvature radius. The thermal reaction of the layer structure is studied by atom probe tomography. Experiments demonstrate that the reaction rate depends significantly on the deposition sequence of metals. Interpretation of the observed reaction kinetics leads to the conclusion that under the influence of interfacial tension probably the two limiting cases of atomic transport, Darken and Nernst-Planck kinetics, are realized in dependence on the stacking sequence.

[Quality of life in long-term survivors after laryngectomy]. / Lebensqualität bei Langzeitüberlebenden nach Laryngektomie.

BACKGROUND: This study was designed to assess the postoperative quality of life (QoL) of 30 patients successfully treated with a laryngectomy. METHODS: QoL was evaluated with two validated questionnaires (EORTC-QLQ-C30 and EORTC-QLQ-H&N35) during the regular outpatient follow-up. To analyse the long-term quality of life, we divided our collective into two groups of patients; one consisting of patients whose treatment had been completed less than five years ago and one whose therapy had been finished more than five years ago. RESULTS: The collective consisted of 24 men (80 %) and 6 (20 %) women with a mean age of 58.8 +/- 8.7 years. Mean follow-up was 53 months (range: 12 - 110). Most patients (n = 15, 50 %) had a tumor stadium IV after UICC. Voice rehabilitation was achieved in all patients with a Provoxreg voice prosthesis. The global QoL was rated as satisfying with a mean value of 62. The analysis of the specific questionnaire showed mostly a limitation of smell. Patients, whose treatment was longer than five years ago, showed a slight improvement in the global QoL. Overall we could not find a significant difference concerning the QoL between the two groups. CONCLUSIONS: In our study the QoL of laryngectomized patients was satisfying. The most common symptoms were problems with smell, cough and dyspnoea.