Mode Coarsening or Fracture: Energy Transfer Mechanisms in Dynamic Buckling of Rods.

We present results of a hybrid experimental, theoretical, and simulation-based investigation of the postbuckling behavior of thin elastic rods axially impacted by a projectile. We find a new postbuckling mechanism: mode coarsening. Much akin to inverse energy cascade phenomena in other nonlinear dynamic systems, energy is transferred during mode coarsening from higher to lower wave numbers-unless the rod breaks, abruptly dissipating in the course of fracture the rod's strain energy. We derive a model that provides a predictive means to capture mode coarsening in the form of a nondissipative, purely geometric force relaxation mechanism, and validate the model by means of molecular dynamics (MD) based structural dynamics simulations for rods of wood and pasta considering different thermodynamic ensembles. The scalability of theory and simulation for engineering applications opens new venues toward safe design of engineering structures subject to impact-induced risks of buckling, ranging from skyscrapers, to aerospace structures, to the crashworthiness of vehicles, for example.

[Research in amyotrophic lateral sclerosis: what is new in 2009?]. / La recherche sur la SLA en 2009 : compte rendu du groupe bibliographique de la coordination des centres SLA.

This paper, written by French amyotrophic lateral sclerosis (ALS) center experts, presents an update of recent advances in fundamental, epidemiological and clinical research in ALS based on a review of the literature between September 2008 and November 2009. Among other pathophysiological mechanisms, the role of stress of the endoplasmic reticulum and the importance of energetic metabolic disturbances have been underscored. In the field of genetics, research has been advanced through the identification of mutations of the gene FUsed in Sarcoma/Translated in LipoSarcoma (FUS/TLS) in individuals with familial and sporadic ALS. This gene is involved in the regulation of transcription, splicing and RNA transport, and has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration. A report showed that mice expressing a mutant form of human TDP-43 develop a progressive and fatal neurodegenerative disease reminiscent of both ALS and frontotemporal lobar degeneration with ubiquitin aggregates (FTLD-U), providing a new animal model that may help to better understand the pathophysiology and test new therapeutics. Beside genetic studies, several epidemiologic studies have investigated the role of environmental factors. A recent study suggests that smoking is a risk factor for developing ALS and it is hypothesized that this could occur through lipid peroxidation via formaldehyde exposure. From a neuroprotective perspective, trials with IGF-1, sodium valproate, coenzyme Q or glatiramer acetate have failed to demonstrate any beneficial effect. A study published in 2008 argued that lithium may have a neuroprotective effect in ALS mice and also in patients. However, two preclinical studies failed to replicate the neuroprotective effect of lithium in ALS mice. Therapeutic trials have been performed or are currently ongoing in Europe and North America. Their results have not yet been published.

[Multiple phenotypic manifestations of X-linked spinobulbar muscular atrophy]. / L'amyotrophie bulbospinale liée à l'X ou maladie de Kennedy: variations phénotypiques.

Recessive X-linked amyotrophic spinobulbar muscular atrophy (SBMA) or Kennedy disease is a neuroendocrine disorder with a slowly progressive phenotype, caused by an expansion of a polymorphic tandem CAG repeat of the androgen receptor gene. Classical clinical hallmarks include onset in the third decade of life, weakness and wasting predominantly in proximal extremity muscles, variable weakness of bulbar muscles, abundant muscle fasciculations, sensory nerve action potential abnormalities and signs of androgen insensitivity such as gynecomastia and testicular atrophy. The diagnosis has been recently made easier by the availability of genetic testing but Kennedy disease is probably still underdiagnosed because of phenotypic variability. We report 11 new cases, of which seven had atypical initial manifestations presenting respectively with myasthenia, cramps and fasciculation syndrome, polyneuropathy, post-trauma monomelic neuronopathy, effort-dependent muscle intolerance and/or muscular dystrophy, with the aim to enlarge the phenotypic spectrum of the published series.

[Update on fundamental and clinical research in amyotrophic lateral sclerosis]. / Actualités dans la recherche fondamentale et clinique sur la sclérose latérale amyotrophique.

This paper from a group of French experts in amyotrophic lateral sclerosis (ALS) presents an update of recent advances in fundamental, epidemiological and clinical research in ALS. Recent development in the pathogenesis of ALS suggests that motor neuron degeneration is a multifactorial and noncell autonomous process. Research has been advanced through the identification of the TAR-DNA-binding protein (TDP-43) as a common neuropathological marker of ALS and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Recently, mutations in the TDP-43 gene have been described in individuals with familial and sporadic ALS. Fundamental research in ALS is expected to lead to the disclosure of new diagnostic markers and therapeutic targets. A small trial has suggested that lithium carbonate may slow ALS progression but larger trials will be needed to confirm these results.

Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study.

BACKGROUND AND PURPOSE: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of patients immediately before death was also determined. METHODS: Information was obtained from neurologists at ALS centres, patients' files, and, when deaths occurred outside a medical facility, attending physicians. RESULTS: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non-invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy. CONCLUSION: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.

Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

BACKGROUND/AIMS: The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. METHODS: We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. RESULTS: The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. CONCLUSION: Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement.

Fatigue in multiple sclerosis is related to disability, depression and quality of life.

Fatigue in multiple sclerosis is a frequent and disabling symptom that can interfere in daily functioning. The aim of this study is to demonstrate the relationship between fatigue and disability, disease course, depression and quality of life. We administered French valid versions of the Fatigue Impact Scale (EMIF-SEP), the short form of the Beck depression inventory (13 items) and the SF-36 to 237 out of 312 patients with clinically definite multiple sclerosis with EDSS

[Ancillary exams in the diagnosis of amyotrophic lateral sclerosis]. / Quelle est la place des autres examens complémentaires?

The diagnosis of ALS is established on the basis of the revised El Escorial criteria revealing involvement of the upper and lower motor neuron. The presence of upper motor neuron signs is recognized by physical examination, but is not always easy to demonstrate. For the patient, early diagnosis reduces the uncertainty and the long waiting period before exclusion test can be performed. Early referral to ALS specialty clinics will have a beneficial effect on the patient's quality of life. Early diagnosis of ALS allows early use of drugs, slowing the rate of disease progression. MR proton spectroscopy and diffusion tensor imaging are potentially useful diagnosis tools but require further analysis of reproducibility in studies with more carefully matched patients and standardized techniques. There is no biochemical marker found in serum or cerebrospinal fluid to establish the definite diagnosis of ALS. Detection of Nogo-A in muscle offers an easy tool for detecting the presence of ALS but further studies are needed to determine the specificity, sensitivity and predictive value of such modifications. When applying standard transcranial magnetic stimulation, examination of several territories improves sensitivity and the probability of detection of infraclinical upper motor neuron dysfunction. The cortical silent period seems most sensitive. The triple stimulation technique (TST) is a very sensitive method but needs to be confirmed by other teams. Some teams have stated that the technique is painful and time consuming for the patient. To date, the corticobulbar tract cannot be studied with TST and we have little experience for the lower limb in very few ALS patients.

[Where is the role of the genetic investigations in amyotrophic lateral sclerosis?]. / Quelle est la place de l'enquête génétique?

About 10 p. cent of amyotrophic lateral sclerosis (ALS) cases are familial. Most of the familial ALS (FALS) cases are clinically homogeneous. Among these families, autosomal dominant, X-linked or autosomal recessive transmission can be observed. Most of the causal mutations have been observed in the SOD1 gene. To date, more than one hundred different mutations have been described, but it remains unclear whether the mutation is always responsible for the phenotype. Penetrance of the mutation depends on age, with almost 90 p. 100 of penetrance at age 70 years. There is no anticipation. Worldwide, the most frequent mutation is A4V with dominant transmission, responsible for a severe, rapid form of the disease. The second most frequent mutation is D90A which is generally transmitted recessively, predominantly in the Scandinavian countries. The phenotype is characterized by a long lasting course (mean: 11 years). Other causal mutations have been described in the Alsine, Apex, NF-H and NAIP genes. Other genes can be considered as risk factors, like SMN2, APO E4, APEX, Dynactine, P-450 D6. Presymptomatic testing for FALS seems difficult because little information can be given to the patient regarding the responsibility of the mutation in the disease, age of onset, and disease trends. The same precautions as for Huntington's disease are needed. Genetic investigations can contribute to better understanding of the pathophysiology of ALS. Other causal genes in the 90 p. 100 of FALS without SOD1 mutation and eventually in the sporadic ALS cases may be disclosed. Genetic investigations also determine the precise role of a given SOD1 mutation because of the large number of potential SOD1 mutations, the variability of the transmission mode and the non-exceptional absence of proven causality for ALS.

[The coverage of the social consequences of the disease and the loss of autonomy in amyotrophic lateral sclerosis]. / La prise en charge des conséquences sociales de la maladie et de la perte d'autonomie.

There is no specific social answer to amyotrophic lateral sclerosis, which alters quickly autonomy of the patients. Different financial and human assistances can be set up to compensate the loss of autonomy. To date, to obtain this assistance, delays are often long; and there is no individual evaluation of the situation at home. The creation of reference centres should allow a better coverage focused on an individualized answer with a management of systems based on the nearness.

Fragmentation as an aggregation process: the role of defects.

A cohesive object will eventually break into fragment when experiencing a strong deformation, during an impact for instance. Using necklaces of cohesive magnetized spheres suddenly expanded, we have shown that the fragmentation of this one-dimensional material results from an inverse aggregation cascade (Vledouts et al. 2015 Proc. R. Soc. A 471, 20150678. (doi:10.1098/rspa.2015.0678)). Here, we explore a variant of this process by changing the force law between the attracting spheres, using hydrogel beads linked by capillary bridges. We also investigate the role of (weak) defects in the cohesion strength and the consequences of a distribution of forces between the beads. It is found that fragment do form by a cascade of aggregations, which is interrupted earlier when the force disorder is stronger.

[Creatine deficiency syndromes]. / Les syndromes de déficit en créatine.

INTRODUCTION: Creatine deficiency syndromes are a newly described group of inborn errors of metabolism affecting creatine metabolism. Three diseases have been described: deficiency of arginine: glycine amidinotransferase (AGAT), deficiency of guanidinoacetate methyltransferase (GAMT) and creatine transporter defect (CRTR). STATE OF ART: These syndromes are characterized by a depletion of creatine/phosphocreatine in the brain. Clinically, most of the patients develop a variable mental retardation and a severe speech delay associated with epilepsy, extra-pyramidal syndrome and behavior disturbances. These diseases are often diagnosed during infancy but a few adult cases have been reported recently. Diagnosis is established by measurement of guanidinoacetate and creatine in biologic fluids and in vivo proton magnetic resonance spectroscopy by the total lack of intra-cerebral creatine/phosphocreatine demonstrating. GAMT and AGAT deficiencies are treatable by oral creatine supplementation whereas patients with CRTR do not respond to the treatment. CONCLUSION: Better knowledge of these syndromes is necessary to optimize diagnosis and patient management of these rare but potentially treatable disorders.

Progression of lower-extremity arterial occlusive disease in type II diabetes mellitus.

The prevalence of lower-extremity arterial occlusive disease (LEAOD), the progression of LEAOD, and the incidence of new LEAOD were determined by noninvasive method in 410 volunteers between the ages of 50 and 70 yr; 252 individuals had type II (non-insulin-dependent) diabetes, 158 were control subjects. LEAOD was monitored with the ankle/arm systolic blood pressure index in combination with Doppler arterial velocity waveform analysis. LEAOD was much more prevalent in the type II patients (22%, 55 of 252) than in the control subjects (3%, 4 of 158) (P less than .00001). The prevalence of risk factors for LEAOD was much higher in the type II patients, including elevated triglyceride, depressed high-density lipoprotein (HDL) cholesterol, hypertension, smoking, and elevated systolic blood pressure. In type II diabetic patients the incidence of new LEAOD over a 2-yr period (14%, 28 of 197) was lower than the incidence of LEAOD progression (87%, 45 of 52). Type II patients with LEAOD also had a high incidence of mortality (22%, 12 of 55) compared with those without LEAOD (4%, 8 of 197) (P less than .0005). A risk score including smoking history, duration of diabetes, depressed HDL cholesterol, total cholesterol, elevated systolic blood pressure, and low obesity index is related to LEAOD. After accounting for the effect of all of the risk factors, we suggest that type II diabetes contributes additional risk for LEAOD.

Chaotic self-trapping of a weakly irreversible double Bose condensate.

We analyze the dynamics of a weakly open Bose-Einstein condensate trapped in a double-well potential. Close to the self-trapping bifurcation, numerical simulations of the weakly irreversible one-dimensional Gross Pitaevskii equation reveal chaotic behaviors. A two-mode model is used to derive amplitude equations describing the complex dynamic of the condensate.

Use of hatch date for broiler breeder production planning.

Data on 109 batches of broiler breeders belonging to six strains and bred in conventional sheds were analyzed to determine the possible influence of natural day length cycle phase on age at start of laying, at sexual maturity, and at peak egg production. The dependence of these variables on date of hatching was characterized by polynomial regression analysis. The resulting equations constitute simple, novel empirical models that are in keeping with current theory on the effects of photoperiod on sexual maturation, and should facilitate production planning in broiler breeder farms.

[Diagnosis and biological monitoring of 6 neurosyphilis cases: value of cerebrospinal fluid analysis]. / Diagnostic et surveillance biologique de six neurosyphilis: apport de l'étude du liquide céphalorachidien.

Our objective is to assess the relevance of the different laboratory findings in cerebrospinal fluid (CSF) and serum for the diagnosis and survey of active neurosyphilis. A retrospective study of six hospitalized neurosyphilitic patients at Neurological Hospital of Lyon from 1987 to 2002 was carried out. Six males were found, aged from 29 to 72 years. Neurosyphilis can be group in two categories: early (meningeal and meningovascular neurosyphilis) and late (progressive general paralysis and tabes dorsalis). All were tertiary stage and HIV negative. We performed in CSF, white and red cell count, cytology, total protein, glucose levels, in CSF and serum, albumin, total IgG, IgA, IgM for calculation of albumin quotient and IgG, IgA and IgM index. Serological tests for syphilis in CSF and serum are VDRL and TPHA. To increase the reliability of treponema antibody tests, the ratio of serum-to-CSF content of albumin is used to assess intrathecal production of treponema antibodies, especially the treponema pallidum hemagglutination assay (TPHA index). The CSF changes in neurosyphilis included elevated cell count with lymphocytic-plasmocytic cell reaction, increased protein content, strongly positive IgG index, numerous positive IgG oligoclonal bands, positive blood and CSF serology. Serological tests are difficult to interpret. Examination of CSF played a major role in the diagnosis and treatment of all forms of neurosyphilis. The CSF abnormalities improved with clinical improvement, especially in meningeal and vascular neurosyphilis, but the response in paresis and tabes was slower or nonexistent. Pleocytosis and protein are indicators of inflammatory activity in the central nervous system and are used as a clinical guide in the diagnostic, for treatment and re-treatment.

[Waldenstrom disease revealed by a peripheral motor neuron disease]. / Révélation d'une maladie de Waldenström par une maladie du neurone moteur périphérique.

BACKGROUND: An association between motor neuron disease and Waldenström disease is rarely reported in the literature. The association with peripheral neuropathy and IgM monoclonal gammapathy is well known. CASE REPORT: In our patient, the malignant monoclonal gammapathy had an unusual antigen pattern. This patient was MAG (myelin-associated glycoprotein) negative but showed a very positive serology for GM1 ganglioside and SGPG (3-sulfated glycuronly paragloboside). DISCUSSION: This is the fifth such case to be reported associated a malignant dyglobulinemia with an MAG-negative IgM gammapathy. It is the first case with positive serology for both the GM1 ganglioside and SGPG.

Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations.

OBJECTIVE: To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations. METHODS: French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations. RESULTS: In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months). CONCLUSION: Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis.