Organisation en réseau et durabilité systémique de deux filières alimentaires

La durabilité des filières alimentaires est questionnée par les pouvoirs publics et les consommateurs, qui tendent à défendre des formes alternatives de production, respectueuses de l'environnement, économiquement et socialement acceptables. Ces formes sont toutefois confrontées à des freins techniques, économiques et institutionnels d'où un questionnement sur leur capacité à se développer et à se maintenir, et donc sur leur durabilité. A partir d'une étude systémique de deux filières alternatives, le petit épeautre de Haute Provence et le riz biologique de Camargue, nous nous sommes attachés à comprendre comment l'organisation des acteurs peut influer sur les trois piliers du développement durable. Nous exposons une manière de considérer le développement durable qui met en avant les relations entre les acteurs, à l'aide de l'outil de l'analyse de réseau, et des entretiens menés avec un échantillon de différents acteurs des filières. Nous montrons que la volonté de pérennisation de la filière influe sur le choix du type d'organisation au sein de la filière, qui peut être orienté pour plus ou moins favoriser la prise en compte des piliers du développement durable. Nos observations montrent l'importance de considérer les réseaux dans une vision systémique de la durabilité. Il reste toutefois difficile d'établir des relations de causalité entre d'une part le type d'organisation et d'autre part la durabilité

c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration.

The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy

Semiology, clustering, periodicity and natural history of seizures in an experimental occipital cortical epilepsy model

Focal neocortical epilepsy is a common form of epilepsy and there is a need to develop animal models that allow the evaluation of novel therapeutic strategies to treat this type of epilepsy. Tetanus toxin (TeNT) injection into the rat visual cortex induces focal neocortical epilepsy without preceding status epilepticus. The latency to first seizure ranged from 3 to 7 days. Seizure duration was bimodal, with both short (approximately 30 s) and long-lasting (>100 s) seizures occurring in the same animals. Seizures were accompanied by non-motor features such as behavioural arrest, or motor seizures with or without evolution to generalized tonic-clonic seizures. Seizures were more common during the sleep phase of a light-dark cycle. Seizure occurrence was not random, and tended to cluster with significantly higher probability of recurrence within 24 h of a previous seizure. Across animals, the number of seizures in the first week could be used to predict the number of seizures in the following 3 weeks. The TeNT model of occipital cortical epilepsy is a model of acquired focal neocortical epilepsy that is well-suited for preclinical evaluation of novel anti-epileptic strategies. We provide here a detailed analysis of the epilepsy phenotypes, seizure activity, electrographic features and the semiology. In addition, we provide a predictive framework that can be used to reduce variation and consequently animal use in preclinical studies of potential treatments

Screening of depression in adolescents through the Internet: Sensitivity and specificity of two screening questionnaires.

.001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CESD (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program

Background: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. Methods: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022. Results: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died. Conclusions: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.</p

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

INTRODUCTION: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). METHODS: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. RESULTS: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. CONCLUSION: This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

Curtailment and Stochastic Curtailment to Shorten the CES-D

The Center for Epidemiologic Studies-Depression (CES-D) scale is a well-known self-report instrument that is used to measure depressive symptomatology. Respondents who take the full-length version of the CES-D are administered a total of 20 items. This article investigates the use of curtailment and stochastic curtailment (SC), two sequential analysis methods that have recently been proposed for health questionnaires, to reduce the respondent burden associated with taking the CES-D. A post hoc simulation based on 1,392 adolescents' responses to the CES-D was used to compare these methods with a previously proposed computerized adaptive testing (CAT) approach. Curtailment lowered average test lengths by as much as 22% while always matching the classification decision of the full-length CES-D. SC and CAT achieved further reductions in average test length, with SC's classifications exhibiting more concordance with the full-length CES-D than do CAT's. Advantages and disadvantages of each method are discussed. © The Author(s) 2012

Fagerstrom test for nicotine dependence vs heavy smoking index in a general population survey

<p>Abstract</p> <p>Background</p> <p>The Fagerström Test for Nicotine Dependence (FTND) is used for assessing nicotine dependence. A shorter test derived from the FTND used for the general population is the Heavy Smoking Index (HSI) (six questions vs. two). The objective of this study is to compare the validity of the HSI versus the FTND.</p> <p>Methods</p> <p>A survey of tobacco use in the general population was carried out in the northern Spanish region of Galicia using both the FTND and the HSI to study a representative sample of 1655 daily smokers. The HSI was compared with the FTND, considered the gold standard. Measures of sensitivity, specificity and predictive values were calculated. Concordance between the tests was also established (Cohen's kappa).</p> <p>Results</p> <p>Cohen's kappa showed good agreement between measures (Kappa = 0.7); specificity values were also high (Sp = 96.2%). Sensitivity analysis in females (Se = 62.3%) did not show good agreement.</p> <p>Conclusions</p> <p>The HSI can be used as a reasonably good screening test in order to identify daily smokers with high nicotine dependence. Nevertheless, for populations or subpopulations having low nicotine dependence, such as women, the FTND is more reliable.</p