(Finite) statistical size effects on compressive strength

The larger structures are, the lower their mechanical strength. Already discussed by Leonardo da Vinci and Edmé Mariotte several centuries ago, size effects on strength remain of crucial importance in modern engineering for the elaboration of safety regulations in structural design or the extrapolation of laboratory results to geophysical field scales. Under tensile loading, statistical size effects are traditionally modeled with a weakest-link approach. One of its prominent results is a prediction of vanishing strength at large scales that can be quantified in the framework of extreme value statistics. Despite a frequent use outside its range of validity, this approach remains the dominant tool in the field of statistical size effects. Here we focus on compressive failure, which concerns a wide range of geophysical and geotechnical situations. We show on historical and recent experimental data that weakest-link predictions are not obeyed. In particular, the mechanical strength saturates at a nonzero value toward large scales. Accounting explicitly for the elastic interactions between defects during the damage process, we build a formal analogy of compressive failure with the depinning transition of an elastic manifold. This critical transition interpretation naturally entails finite-size scaling laws for the mean strength and its associated variability. Theoretical predictions are in remarkable agreement with measurements reported for various materials such as rocks, ice, coal, or concrete. This formalism, which can also be extended to the flowing instability of granular media under multiaxial compression, has important practical consequences for future design rules.Owing to its importance for structural design (1), the elaboration of safety regulations (2), or the extrapolation of laboratory results to geophysical field scales (3), the size effects on strength of materials are one of the oldest problems in engineering, already discussed by Leonardo da Vinci and Edmé Mariotte (4) several centuries ago, but still an active field of research (5, 6). As early as 1686, Mariotte (4) qualitatively introduced the weakest-link concept to account for size effects on mechanical strength, a phenomenon evidenced by Leonardo da Vinci almost two centuries earlier. This idea, which states that the larger the system considered is, the larger the probability to find a particularly faulty place that will be at the origin of global failure, was formalized much later by Weibull (7). Considering a chain of elementary independent links, the failure of the chain is obtained as soon as one link happens to break. By virtue of the independence between the potential breaking events, the survival probability of a chain of N links is obtained by the simple multiplication of the N elementary probabilities. Depending on the properties of the latter, the global survival probability converges toward one of the three limit distributions identified by Weibull (7), Gumbel (8), and Fréchet (8), respectively. Together with Fisher and Tippett (9), these authors pioneered the field of extreme value statistics.This purely statistical argument, undoubtedly valid in 1D, was extended by Weibull (7, 10) to account for the risk of failure of 3D samples or structures. Besides the hypothesis of independence, it thus requires an additional hypothesis of brittleness: The nucleation of any elementary crack at the microscopic scale from a preexisting flaw is assumed to immediately induce the failure at the macroscale. More specifically, following linear elastic fracture mechanics (LEFM) stating that crack initiation from a flaw of size s occurs at a stress , one gets a probability of failure of a system of size L under an applied stress σ, , that depends on the distribution of preexisting defect sizes. Assuming a power law tail for this distribution, Weibull statistics are expected(7), , whereas Gumbel statistics are expected for any distribution of defect sizes whose the tail falls faster than that of a power law (8, 11, 12), , where m is the so-called Weibull’s modulus, d is the topological dimension, and L₀ and σ_u are normalizing constants. For Weibull statistics, the mean strength and the associated SD δ(σ_f) then scale with sample size L as . This approach has been successfully applied to the statistics of brittle failure strength under tension (7, 13), with m in the range 6–30 (14). It implies a vanishing strength for L → +∞, although this decrease can be rather shallow, owing to the large values of m often reported.Although relying on strong hypotheses, this weakest-link statistical approach was almost systematically invoked until the 1970s to account for size effects on strength whatever the material and/or the loading conditions. However, as shown by Bazant (1, 5), in many situations the hypothesis of brittleness is not obeyed. This is in particular the case when the size of the fracture process zone (FPZ) becomes nonnegligible with respect to the system size. In this so-called quasi-brittle case, an energetic, nonstatistical size effect applies (15), which has been shown to account for a large variety of situations (5). Toward large scales, i.e., L → +∞, the FPZ becomes negligible compared with L, and the hypothesis of brittleness should therefore be recovered and statistical size effects should dominate. Statistical numerical models of fracture of heterogeneous media also revealed deviations from the extreme value statistics predictions (16) but, as stated by Alava et al. (ref. 11, p. 9), “the role of damage accumulation for fracture size effects in unnotched samples still remains unclear.” As shown below, compressive failure results from such progressive damage accumulation.In what follows, we do not consider (deterministic) energetic size effects and explore a situation, compressive failure, where both the hypotheses of brittleness (in the sense given above) and independence are not fulfilled, up to very large scales. Relaxing these initial hypotheses of the weakest-link theory, our statistical physics approach remains statistical by nature and relies on the interplay between internal disorder and stress redistributions. It is based on a mapping of brittle compressive failure onto the critical depinning transition of an elastic manifold, a class of models widely used in nonequilibrium statistical physics characterized by a dynamic phase transition (17). This approach does not consider a sample’s shape effects (18), only statistical size effects. The critical scaling laws associated to this phase transition naturally predict a saturation of the compressive strength at a large scale and are in remarkable agreement with measurements reported for various materials such as rocks, ice, coal, or concrete.     

Frovatriptan vs. other triptans for the acute treatment of oral contraceptive-induced menstrual migraine: pooled analysis of three double-blind,randomized, crossover,multicenter studies

Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1–3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans.     

Langerhans cell histiocytosis is a neoplasm and consequently its recurrence is a relapse: In memory of Bob Arceci

Langerhans cell histiocytosis (LCH) remains a poorly understood disorder with heterogeneous clinical presentations characterized by focal or disseminated lesions that contain excessive CD1a+ langerin+ cells with dendritic cell features known as “LCH cells.” Two of the major questions investigated over the past century have been (i) the origin of LCH cells and (ii) whether LCH is primarily an immune dysregulatory disorder or a neoplasm. Current opinion is that LCH cells are likely to arise from hematopoietic precursor cells, although the stage of derailment and site of transformation remain unclear and may vary in patients with different extent of disease. Over the years, evidence has provided the view that LCH is a neoplasm. The demonstration of clonality of LCH cells, insufficient evidence alone for neoplasia, is now bolstered by finding driver somatic mutations in BRAF in up to 55% of patients with LCH, and activation of the RAS‐RAF‐MEK‐ERK (where MEK and ERK are mitogen‐activated protein kinase and extracellular signal‐regulated kinase, respectively) pathway in nearly 100% of patients with LCH. Herein, we review the evidence that recurrent genetic abnormalities characterized by activating oncogenic mutations should satisfy prerequisites for LCH to be called a neoplasm. As a consequence, recurrent episodes of LCH should be considered relapsed disease rather than disease reactivation. Mapping the complete genetic landscape of this intriguing disease will provide additional support for the conclusion that LCH is a neoplasm and is likely to provide more potential opportunities for molecularly targeted therapies.     

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study

BackgroundA surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence.AimsTo assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up.MethodsA multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT.ResultsA total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038).ConclusionsPET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.     

Digestive lesions related to N.S.A.I.D. (epidemiology and prevention)]

The frequency of gastrointestinal ulcers and ulcers complications induced by non steroidal anti inflammatory drugs (NSAID) increases continuously. This is a major health problem, since 1.5% of general population (mostly elderly people) take regularly NSAID'S. NSAID'S gastropathy is asymptomatic in nearly 50% of cases, even in case of big gastric ulcer. A severe hemorrhage or a gastric perforation can occurred in the absence of previous symptoms. When the patient had epigastric symptoms during a treatment with NSAID'S, upper GI endoscopy is normal in 50% of cases. NSAID'S are ulcerogenic by decreasing the capacity of the gastric mucosa to produce prostaglandin (PG) and by weakening gastric mucosal barrier. H2 blockers are not effective to prevent such lesions. Elderly women, are at high risk of gastric mucosal lesions and complications. In a prospective study, it was shown that misoprostol was effective to reduce the rate of NSAID'S induced gastric and duodenal ulcers. Up to date, epidemiologic studies don't show any population group at no risk of NSAID'S induced gastric lesions. The actual problem, now, is to determine which groups of patients are at high risk of complication in order to clarify the indications of preventive treatment. Today, in France, it's believed that old patients, with organic pathology (respiratory, cardiac, hepatic or urinary) and/or using two or more NSAID'S are at high risk.     

Genomic Definition of Hypervirulent and Multidrug-Resistant Klebsiella pneumoniae Clonal Groups

Multidrug-resistant and highly virulent Klebsiella pneumoniae isolates are emerging, but the clonal groups (CGs) corresponding to these high-risk strains have remained imprecisely defined. We aimed to identify K. pneumoniae CGs on the basis of genome-wide sequence variation and to provide a simple bioinformatics tool to extract virulence and resistance gene data from genomic data. We sequenced 48 K. pneumoniae isolates, mostly of serotypes K1 and K2, and compared the genomes with 119 publicly available genomes. A total of 694 highly conserved genes were included in a core-genome multilocus sequence typing scheme, and cluster analysis of the data enabled precise definition of globally distributed hypervirulent and multidrug-resistant CGs. In addition, we created a freely accessible database, BIGSdb-Kp, to enable rapid extraction of medically and epidemiologically relevant information from genomic sequences of K. pneumoniae. Although drug-resistant and virulent K. pneumoniae populations were largely nonoverlapping, isolates with combined virulence and resistance features were detected.     

Intraoperative blood loss during decompressive craniectomy for intractable intracranial hypertension after severe traumatic brain injury in children

Purpose

There are no data available on the risk of intraoperative bleeding during decompressive craniectomy (DC) after traumatic brain injury (TBI) in children. The objectives of this study were to assess the risk of intraoperative bleeding during DC for intractable intracranial hypertension after TBI, to identify potential factors associated with the risk of bleeding during DC, and to assess the impact of DC on systemic and cerebral hemodynamics and on coagulation.

Methods

Twelve children were identified as having undergone DC after TBI from April 2009 to June 2013 in our center. Subjects were allocated into two groups according to the percentage of blood loss (IBL) during the intraoperative period (<or ≥50 % of the estimated blood volume (EBV)).

Results

The median IBL during DC was 49 [17–349] % of the EBV. Children with an IBL?≥?50 % of EBV had higher preoperative intracranial pressure (ICP) (p?=?0.03) and international normalized ratio (INR) (p?=?0.02) than those with an IBL?<?50 % of EBV. DC induced significant decreases in ICP (p?=?0.0005), mean arterial pressure (p?=?0.01), and a significant increase in norepinephrine flow rate (p?=?0.04) between the immediate pre- and postoperative periods.

Conclusions

DC allows a significant decrease in ICP after severe pediatric TBI but is a surgical procedure at a high risk of bleeding. High ICP and INR during the immediate preoperative period are the main factors associated with increased IBL during DC. Further studies are needed to confirm our results and to assess the impact of the amount of IBL on the postoperative survival and functional outcome.     

Multiplex PCR for Detection of Seven Virulence Factors and K1/K2 Capsular Serotypes of Klebsiella pneumoniae

A single multiplex PCR assay targeting seven virulence factors and the wzi gene specific for the K1 and K2 capsular serotypes of Klebsiella pneumoniae was developed and tested on 65 clinical isolates, which included 45 isolates responsible for community-acquired severe human infections. The assay is useful for the surveillance of emerging highly virulent strains.