Ultrahigh Strength and Plasticity Mechanisms of Si and SiC Nanoparticles Revealed by First-Principles Molecular Dynamics.

It is now well established that materials are stronger when their dimensions are reduced to the submicron scale. However, what happens at dimensions such as a few tens of nanometers or lower remains largely unknown, with conflicting reports on strength or plasticity mechanisms. Here, we combined first-principles molecular dynamics and classical force fields to investigate the mechanical properties of 1-2 nm Si and SiC nanoparticles. These compression simulations unambiguously reveal that the strength continues to increase down to such sizes, and that in these systems the theoretical bulk strength can be reached or even exceeded in some cases. Most of the nanoparticles yield by amorphization at strains greater than 20%, with no evidence of the ß-tin phase for Si. Original and unexpected mechanisms are also identified, such as the homogeneous formation of a dislocation loop embryo for the ⟨111⟩ compression of SiC nanoparticles, and an elastic softening for the ⟨001⟩ compression of Si nanoparticles.

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.

BACKGROUND: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%. MATERIALS AND METHODS: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests. RESULTS: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable. CONCLUSIONS: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

[Medical biostatistics with GMRC Shiny Stats - learning by doing]. / Biostatistiques médicales avec GMRC Shiny Stats ­ un outil de formation par la pratique.

Biostatistics are omnipresent in the scientific and medical literature and are an essential skill for any health student. We have developed a practical training tool - GMRC Shiny stats - an interactive application specifically dedicated to medical data statistical analysis. The application has been designed to provide an analysis workflow corresponding to the usual progression of an experienced statistician during data analysis. The most common statistical analyses can be performed (descriptive statistics, inferences according to frequentist methods, survival analyses, correlation, agreement measurements, etc.). GMRC Shiny stats is intuitive and user-friendly and assists students in choosing the most appropriate statistical tests. With all these functionalities, students can learn statistical analysis by doing. Getting involved in the statistical analysis and processing of their own data is likely to improve their biostatistics skills.

Critical shoulder angle: Measurement reproducibility and correlation with rotator cuff tendon tears.

BACKGROUND: Associations have been reported linking rotator cuff tears (RCTs) to both greater lateral extension of the acromion and greater inclination of the glenoid cavity. These two factors combined can be assessed using a recently introduced parameter, the critical shoulder angle (CSA). The primary objective of this study was to confirm the association linking a high CSA value to RCTs, and the secondary objective was to assess the reproducibility of CSA measurement using a goniometer. HYPOTHESIS: The null hypothesis was that the CSA value in a group of patients with RCTs was not significantly different from that in patients with anterior shoulder instability and a Bankart lesion, taken as the general population for this study. METHODS: After a power estimation, we retrospectively included 28 patients with a mean age of 55.5 years who had surgery for RCTs and 27 patients with a mean age of 27.2 years who underwent anterior labral repair. Two surgeons used a goniometer to measure the CSA in each patient. Reproducibility was assessed based on Bland-Altman plots and Pearson's correlation coefficient. RESULTS: The mean CSA was significantly higher (P=0.02) in the RCT group (36.4°±4.4°; range: 30°-46°) than in the labral-repair group (33.3°±3.8°; range: 25°-41°). Intra-observer reproducibility was 96.7% and inter-observer reproducibility was 95.5%. CONCLUSION: Our results support previously published evidence that the CSA is significantly greater in patients with RCTs. Thus, an anatomical difference seems to exist between patients with RCTs and the general population. The CSA measured on a standard radiograph using a goniometer provides a reproducible assessment of this anatomical difference. LEVEL OF EVIDENCE: IV, case-control epidemiological study with a power estimation.

Can the presence of an infection be predicted before a revision total hip arthroplasty? Preliminary study to establish an infection score.

INTRODUCTION: The diagnosis of periprosthetic joint infection can be challenging, in part because there is no universal diagnostic test. Current recommendations include several diagnostic criteria, and are mainly based on the results of deep microbiological samples; however, these only provide a diagnosis after surgery. A predictive infection score would improve the management of revision arthroplasty cases. The purpose of this study was to define a composite infection score using standard clinical, radiological and laboratory data that can be used to predict whether an infection is present before a total hip arthroplasty (THA) revision procedure. HYPOTHESIS: The infection score will make it possible to differentiate correctly between infected and non-infected patients in 75% of cases. MATERIAL AND METHODS: One hundred and four records from patients who underwent THA revision for any reason were analysed retrospectively: 43 with infection and 61 without infection. There were 54 men and 50 women with an average age of 70±12 years (range 30-90). A univariate analysis was performed to look for individual discriminating factors between the data in the medical records of infected and non-infected patients. A multivariate analysis subsequently integrated these factors together. A composite score was defined and its diagnostic effectiveness was evaluated as the percentage of correctly classified records, along with its sensitivity and specificity. RESULTS: The score consisted of the following individually weighed factors: body mass index, presence of diabetes, mechanical complication, wound healing disturbance and fever. This composite infection score was able to distinguish correctly between the infected patients (positive score) and non-infected patients (negative score) in 78% of cases; the sensitivity was 57% and the specificity 93%. DISCUSSION: Once this score is evaluated prospectively, it could be an important tool for defining the medical - surgical strategy during THA revision, no matter the reason for revision. LEVEL OF EVIDENCE: Level IV - retrospective study.

Reverse Transcriptase in Action: FRET-Based Assay for Monitoring Flipping and Polymerase Activity in Real Time.

Reverse transcriptase (RT) of human immunodeficiency virus-1 (HIV-1) is a multifunctional enzyme that catalyzes the conversion of the single stranded viral RNA genome into double-stranded DNA, competent for host-cell integration. RT is endowed with RNA- and DNA-dependent DNA polymerase activity and DNA-directed RNA hydrolysis (RNase H activity). As a key enzyme of reverse transcription, RT is a key target of currently used highly active antiretroviral therapy (HAART), though RT inhibitors offer generally a poor resistance profile, urging new RT inhibitors to be developed. Using single molecule fluorescence approaches, it has been recently shown that RT binding orientation and dynamics on its substrate play a critical role in its activity. Currently, most in vitro RT activity assays, inherently end-point measurements, are based on the detection of reaction products by using radio-labeled or chemically modified nucleotides. Here, we propose a simple and continuous real-time Förster resonance energy transfer (FRET) based-assay for the direct measurement of RT's binding orientation and polymerase activity, with the use of conventional steady-state fluorescence spectroscopy. Under our working conditions, the change in binding orientation and the primer elongation step can be visualized separately on the basis of their opposite fluorescence changes and their different kinetics. The assay presented can easily discriminate non-nucleoside RT inhibitors from nucleoside RT inhibitors and determine reliably their potency. This one-step and one-pot assay constitutes an improved alternative to the currently used screening assays to disclose new anti-RT drugs and identify at the same time the class to which they belong.

French policy for managing the post-accident phase of a nuclear accident.

In 2005, at the request of the French Government, the Nuclear Safety Authority (ASN) established a Steering Committee for the Management of the Post-Accident Phase of a Nuclear Accident or a Radiological Emergency, with the objective of establishing a policy framework. Under the supervision of ASN, this Committee, involving several tens of experts from different backgrounds (e.g. relevant ministerial offices, expert agencies, local information commissions around nuclear installations, non-governmental organisations, elected officials, licensees, and international experts), developed a number of recommendations over a 7-year period. First published in November 2012, these recommendations cover the immediate post-emergency situation, and the transition and longer-term periods of the post-accident phase in the case of medium-scale nuclear accidents causing short-term radioactive release (less than 24 h) that might occur at French nuclear facilities. They also apply to actions to be undertaken in the event of accidents during the transportation of radioactive materials. These recommendations are an important first step in preparation for the management of a post-accident situation in France in the case of a nuclear accident.

Posterior surgery in high-grade spondylolisthesis.

INTRODUCTION: High-grade L5-S1 spondylolisthesis alters sagittal spinopelvic balance, which can cause low back pain and progressive neurologic disorder. The present study assessed spondylolisthesis reduction and maintenance over time with L4-S1 versus L5-S1 fusion using a lever-arm system and posterior fusion combined with lumbosacral graft. MATERIALS AND METHODS: Forty patients were operated on for symptomatic high-grade spondylolisthesis, 34 of whom had full pre- and post-operative radiological analysis, with a mean follow-up of 5.4years. There were 9 L5-S1 and 25 L4-S1 instrumentations. Analysis of spinopelvic and slipping parameters and the evolution of segmental lordosis compared results between L5-S1 and L4-S1 instrumentation. RESULTS: Mean Taillard spondylolisthesis index decreased from 64% to 37% (P=0.0001). Overall sagittal spinopelvic balance was not significantly changed. Overall L1-S1 and segmental L4-L5 lordosis were not affected by instrumentation. Mean L5-S1 segmental lordosis increased from 11° to 18°. There was loss of reduction from 19° to 14° with L5-S1 instrumentation, in contrast to maintained reduction with L4-S1 instrumentation (P=0.006). CONCLUSION: The lever-arm system provided anterior-posterior reduction of spondylolisthesis and corrected slippage. Postoperative change in overall sagittal spinopelvic balance was slight and constant. Posterior L4-S1 fusion provided better long-term control of L5-S1 lordosis reduction than the shorter L5-S1 fusion. Retrospective study of level IV.

[Pseudolymphoma of the skin: ambiguous terminology: a survey among dermatologists and pathologists]. / Le pseudolymphome cutané: une sémantique ambiguë. Enquête auprès des dermatologues et des pathologistes.

BACKGROUND: Cutaneous pseudolymphomas (CPL) are diseases that simulate cutaneous lymphomas both clinically and histologically but have a benign course. It can be very difficult, if not impossible, to differentiate pseudolymphoma from lymphoma and there is some semantic ambiguity about the term pseudolymphoma. The aim of this study was to determine the exact meaning attributed to the term pseudolymphoma by a representative sample of French dermatologists and pathologists. MATERIALS AND METHODS: We designed two types of questionnaire, one for dermatologists and the other for pathologists, and sent them out to 274 dermatologists and to 110 pathologists. RESULTS: We received responses from 122 dermatologists (44.5%) and 64 pathologists (58.1%). In the dermatologist group, 56% consider that CPL is not a clearly defined entity, while 58% consider it a benign disease and only 18% feel that most CPLs are related to a precise cause; 72% of dermatologists perform a routine checkup, 58% initiate treatment and 84% conduct follow-up in the case of CPL. Among pathologists, 61% consider that CPL is not a clearly defined entity, 82% feel that cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia and cutaneous lymphocytoma are the same entity, and 75% consider that CPL are benign; 92% perform routine immunohistochemistry studies and only 26% screen for clonality. Bivariate statistical analysis showed that pathologists consider pseudolymphomas as benign entities frequently than dermatologists (χ(2) test: P=0.02; Fisher's exact test: P=0.01) and that there are more pathologists than dermatologists who see more than four pseudolymphomas per year (χ(2) test: P<0.001; Fisher's exact test: P<0.001). Multivariate analysis clearly identified a tendency among doctors viewing pseudolymphomas as a distinct entity to also consider them benign (Odds Ratio 0.29, CI 97.5% 0.14-0.58), irrespective of speciality or type of practice (hospital practice, private practice or both). DISCUSSION: This study demonstrates that, in France, the term pseudolymphoma is an ambiguous notion. We believe that cases in which it is impossible to differentiate pseudolymphoma from cutaneous lymphoma should be referred to as lymphoproliferations of undetermined significance, since more than 50% of physicians consider that the term pseudolymphoma designates a resolutely benign entity.

A new parametrization of the Stillinger-Weber potential for an improved description of defects and plasticity of silicon.

A new parametrization of the widely used Stillinger-Weber potential is proposed for silicon, allowing for an improved modelling of defects and plasticity-related properties. The performance of the new potential is compared to the original version, as well as to another parametrization (Vink et al 2001 J. Non-Cryst. Solids, 282 248), in the case of several situations: point defects and dislocation core stability, threshold displacement energies, bulk shear, generalized stacking fault energy surfaces, fracture, melting temperature, amorphous structure, and crystalline phase stability. A significant improvement is obtained in the case of dislocation cores, bulk behaviour under high shear stress, the amorphous structure, and computation of threshold displacement energies, while most of the features of the original version (elastic constants, point defects) are retained. However, despite a slight improvement, a complex process like fracture remains difficult to model.

Preoperative phlebography in anterior L4-L5 disc approach. Clinical experience about 63 cases.

INTRODUCTION: The anterior approach of the L4-L5 disc requires a perfect knowledge of the venous anatomy. Some configurations make this approach hazardous. The purpose of this study is to classify configurations of the iliocava junction and the iliolumbar vein relative to L4-L5 and to analyze vascular complications. MATERIALS AND METHODS: The preoperative phlebographies of 63 patients (30 men, 33 women, mean age 42years) undergoing a L4-L5 disc replacement were reviewed. The height of the iliocava junction was calculated as a ratio of the distance between the discs L4-L5 and L5-S1. The position of the left iliac vein was classified into three thirds across the width of L5. The number of branches of the iliolumbar vein was noted. Surgical reports were reviewed for complications. RESULTS: The height of the iliocava junction was very high in six, high in 25, low in 26 and very low in six patients. The position of the left iliac vein was medial in 20, intermediate in 28 and lateral in 15 patients. The iliolumbar vein had one branch in 37, two in 20, three in three patients. It was not visualized in three cases. Variants of the venous anatomy included eight duplications of the left iliac vein, four wide diameters and one iliolumbar vein network pattern. Intraoperatively, three lacerations of iliolumbar veins occurred. CONCLUSION: The iliocava anatomy is very variable: the safety of an anterior approach to the L4-L5 disc depends on it. The information of preoperative phlebography can help to plan a more accessible antero-lateral approach or to switch on a posterior fusion if the anatomical situation is deemed too dangerous, such as duplicated left iliac veins. LEVEL OF EVIDENCE: Level IV. Diagnostic study.

Is preoperative embolization a prerequisite for spinal metastases surgical management?

BACKGROUND: Preoperative embolization decreases the intraoperative risk of hemorrhage in spinal decompression surgery of hypervascular metastases such as renal cell carcinoma. There is no consensus concerning embolization in other metastases. The purpose of this study was to compare the intraoperative amount of blood loss in embolized versus non-embolized patients, seeking for differences depending on the primary tumor and the extent of surgery. PATIENTS AND METHODS: Ninety-three patients, average age 60.5 years, were operated. The origins of metastases were: 28 breast cancer (30.1%), 19 pulmonary carcinoma (20.4%), 16 renal cell carcinoma (17.2%), 30 other cancers (32.3%). Surgical procedures were: 52 thoracolumbar laminectomies with instrumentation, 29 thoracolumbar corpectomies or vertebrectomies, 12 cervical corpectomies. A preoperative microsphere embolization was performed in 35 patients. Blood loss was evaluated by: blood volume in surgical aspiration devices, number of transfused packed red blood cells units and hemoglobin variation during surgery. RESULTS: Renal metastases were systematically embolized. In the breast group, there was no significant difference (P>0.05) in blood loss between embolization versus non-embolization. In the pulmonary group and in other metastases, no difference was found either. The extent of surgery (corpectomy/vertebrectomy versus thoracolumbar instrumentation and cervical corpectomy) increased bleeding: breast 1775ml versus 778ml and 600ml respectively (P=0.048), pulmonary 2500ml versus 430ml and 180ml (P=0.020), renal 3346ml versus 1175ml and 780ml (P=0.036) and others 1550ml versus 474ml and 400ml (P=0.020). CONCLUSIONS: Embolization decreases the risk of hemorrhage in highly vascularized metastases such as renal cell carcinoma. A benefit of embolization was not found for metastases of breast or pulmonary tumors. As far as other metastases, thyroid carcinoma should be analyzed on a greater cohort. The extent of surgery remains an important risk factor for intraoperative bleeding. A preoperative angiogram should be carried out in all types of metastases prior to a thoracolumbar corpectomy or vertebrectomy to perform an embolization if the tumor is hypervascular. LEVEL OF EVIDENCE: Level IV, retrospective study.

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures.

Investigation of the interaction between hydrogen and screw dislocation in silicon by first-principles calculations.

The stability of atomic and molecular hydrogen in the vicinity of a screw dislocation in silicon has been investigated using first-principles calculations. The lowest energy configurations are obtained for H atoms located in the dislocation core, suggesting that the segregation of hydrogen is favoured in the dislocation core. It is found that a spontaneous dissociation of H(2) could occur in the dislocation core. Finally, the variation of the interaction energy between hydrogen and the dislocation core as a function of the separation distance has been calculated. There is no sizeable interaction variation for H(2). However, in the case of a single H, an inverse law has been obtained, which can be explained by the anisotropic stress field generated by the insertion of H in the silicon lattice.

Binary rototranslational hyper-Rayleigh spectra of H(2)-He gas mixture.

The collision-induced rototranslational hyper-Rayleigh spectra of gaseous H(2)-He mixture are computed and discussed in the binary regime. As the input data we use our ab initio computed H(2)-He collision-induced first dipole hyperpolarizability tensor Deltabeta(R). Both the vector and the septor part of the H(2)-He hyper-Rayleigh spectra are evaluated at room temperature (T=295 K). The spectra are calculated assuming the full quantum computations based on the Schrödinger equation of the relative translational motion in the isotropic H(2)-He potential as well as using semiclassical methods.

[The control of radiation protection in the field of radiotherapy by the French Nuclear Safety Authority (ASN)]. / Les actions de contrôle de l'Autorité de sûreté nucléaire (ASN) dans le domaine de la radiothérapie.

During the last months, several incidents at radiotherapy services occurred in France; one of these accidents led to the death of several patients or required further heavy surgical acts. In this context, ASN (Autorité de sûreté nucléaire) issued an experimental guide for the notification of radiation protection events and achieved, in dialogue with professional organisations, a new scale intended to facilitate public information on radiotherapy incidents. ASN is also fully involved in the preparation of the action plan managed by the Health ministry in order to improve the safety of treatment in radiotherapy.

Hyper-Rayleigh spectral intensities of gaseous Kr-Xe mixture.

Binary collision-induced hyper-Rayleigh (CIHR) spectra of Kr-Xe gaseous system are computed quantum mechanically and classically within the frequency range up to 380 cm(-1). The intensities are expressed in absolute units. The details of the theory developed for the CIHR spectra are given and the properties of the profiles as well as the depolarization ratio frequency dependence are discussed. The contributions to the spectra related to the vector b10(r) and the septor b30(r) components of the hyperpolarizability tensor are evaluated.

A locus for autosomal dominant colobomatous microphthalmia maps to chromosome 15q12-q15.

Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040.