Chromosomal control of pig populations in France: 2002-2006 survey

The chromosomal control of pig populations has been widely developed in France over the last ten years. By December 31st, 2006, 13 765 individuals had been karyotyped in our laboratory, 62% of these since 2002. Ninety percent were young purebred boars controlled before service in artificial insemination centres, and 3% were hypoprolific boars. So far, 102 constitutional structural chromosomal rearrangements (67 since 2002) have been described. Fifty-six were reciprocal translocations and 8 peri- or paracentric inversions. For the first time since the beginning of the programme and after more than 11 000 pigs had been karyotyped, one Robertsonian translocation was identified in 2005 and two others in 2006. The estimated prevalence of balanced structural chromosomal rearrangements in a sample of more than 7700 young boars controlled before service was 0.47%. Twenty-one of the 67 rearrangements described since 2002 were identified in hypoprolific boars. All were reciprocal translocations. Twelve mosaics (XX/XY in 11 individuals, XY/XXY in one individual) were also diagnosed. Two corresponded to hypoprolific boars, and three to intersexed animals. The results presented in this communication would justify an intensification of the chromosomal control of French and, on a broader scale, European and North-American pig populations

Small-World Networks: Is there a mismatch between theory and practice?

In small-world networks, each peer is connected to its closest neighbors in the network topology, as well as to additional long-range contact(s), also called shortcut(s). In 2000, Kleinberg showed that greedy routing in a $n$ peer small-world network, performs in $O(n^\frac{1}{3})$ steps when the distance to shortcuts is chosen uniformly at random, and in $O(\log^2n)$ when the distance to shortcuts is chosen according to a harmonic distribution in a $d$-dimensional mesh. Yet, we observe through experimental results that peer to peer gossip-based protocols achieving small-world topologies where shortcuts are randomly chosen, perform well in practice. The motivation of this paper is to explore this mismatch and attempt to reconcile theory and practice in the context of small-world overlay networks. More precisely, based on the observation that, despite the fact that the routing complexity of gossip-based small-world overlay networks is not polylogarithmic (as proved by Kleinberg), this type of networks ultimately provide reasonable results in practice. This leads us to think that the asymptotic big $O()$ complexity alone might not always be sufficient to assess the practicality of a system. The paper consequently proposes a refined routing complexity measure for small-world networks. Simulation results confirm that random selection of shortcuts can achieve ``practical'' systems. Then, given that Kleinberg proved that the distribution of shortcuts has a strong impact on the routing complexity, arises the question of leveraging this result to improve upon current gossip-based protocols. We show that it is possible to design gossip-based protocols providing a good approximation of Kleinberg-like small-world topologies. Along, are presented simulation results that demonstrate the relevance of the proposed approach

D2HT: the best of both worlds, Integrating RPS and DHT

International audienceDistributed Hash Tables (DHTs) and Random Peer Sampling (RPS) provide important and complementary services in the area of P2P overlay networks. DHTs achieve efficient lookup while RPS enables nodes to build and maintain connectivity in the presence of high churn. Clearly, many applications, e.g. in the area of search, would greatly benefit if both these services were available together at a reasonable cost. This paper integrates a structured P2P overlay and a Random Peer Sampling service through gossip protocols. This system called D2HT, leverages the small-world nature of DHTs and relies on two cohabiting gossip protocols maintaining the close and long-range links respectively. The long links are chosen according to a harmonic distribution, following the Kleinberg small-world model. This approach exhibits several benefits: (i) The resulting DHT is highly dynamic and self-stabilizing, changes are tracked for free through the gossip nature of the protocol. This removes the need for complex, usually disjoint, and expensive join and repair procedures. Yet, it achieves reasonable routing performance with respect to standard DHTs; (ii) The resulting peer sampling service provides a biased sampling following a harmonic distribution: this improves the routing without jeopardizing the quality of the RPS. The set of long-range links which are a source of RPS can be used independently by others applications for free. They change continuously, achieving well-balanced routing across the nodes. We perform extensive simulations and compare the performances of D2HT with Cyclon, HRing, Symphony and Pastry to demonstrate the gains achieved by the approach proposed in this paper

Nonmotor Symptoms in Parkinson’s Disease in 2012: Relevant Clinical Aspects

Nonmotor symptoms (NMSs) of Parkinson's disease (PD) are common, but they are often underrecognized in clinical practice, because of the lack of spontaneous complaints by the patients, and partly because of the absence of systematic questioning by the consulting physician. However, valid specific instruments for identification and assessment of these symptoms are available in 2012. The administration of the self-completed screening tool, NMSQuest, associated with questioning during the consultation, improves the diagnosis of NMSs. NMSs play a large role in degradation of quality of life. More relevant NMSs are described in this review, mood disorders, impulse control disorders, cognitive deficits, hallucinations, pain, sleep disorders, and dysautonomia

EIF4G1 in familial Parkinson's disease: pathogenic mutations or rare benign variants?

International audienceMutations in the eukaryotic translation initiation factor 4-gamma (EIF4G1) gene, encoding a component of the eIF4F translation initiation complex, were recently reported as a possible cause for the autosomal dominant form of Parkinson's disease (PD). Here, we describe the screening of all 31 EIF4G1 coding exons in a series of 251 index cases with autosomal dominant PD, mostly of French origin and in 236 European control subjects. We identified 12 rare coding variants (either nonsynonymous amino acid substitutions or in frame deletions/insertions), including 6 variants present only in cases and 3 in controls. Segregation was possible only for 1 variant (p.E462delInsGK) that was found in 2 affected siblings. In addition, we found 2 previously reported pathogenic variants in 2 isolated patients (p.G686C) and in a control subject (p.R1197W). These data do not support the pathogenicity of several EIF4G1 variants in PD, at least in the French population

From scientific models to companion modelling: engaging a dialogue with local actors in an Amazonian floodplain about biodiversity management at a territorial level

The Amazonian floodplain is among the most productive and diversified ecosystems in the world. The moving littoral enables a rapid nutrient recycling, explaining the large productivity and biodiversity of the system. Attracted by such favourable conditions for agricultural activities and fishing, populations have settled in the floodplains and developed complementary activities to cope with important variations in their environment, between the flood season and the dry season. However, in the past decades, the rhythm of these floodplains has changed, obliging the actors to deal with great uncertainty. Based on several years of hydrological and biogeochemical studies to understand the reasons of these environmental changes, the “life scientists” of our team invited the “social scientists” with the following question: Can the results about the dynamics of these floodplains help local populations better anticipate the future fluctuations of the river and adapt their activities to be less vulnerable to such change? To address this, we first chose to turn the perspective around: what were the preoccupations and strategies of local populations and what did they expect from scientists? The challenge was to enable the perceptions and knowledge of local populations to dialogue with scientific knowledge. Based on a Companion Modelling approach, we engaged a participatory process to collectively discuss the current situation and possible future scenarios. Using a role-playing game as an interface for this dialogue, we have progressively built a model to integrate both the knowledge of the local actors regarding their practices and possible environmental impacts and the knowledge of the scientists on environmental dynamics. This has obliged researchers to learn to work together and simplify their knowledge, and requires finding common points of interest with local populations, translating “biodiversity” into concrete issues that have a meaning for local actors. (Texte intégral

Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS)

Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

BACKGROUND The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. METHODS AND FINDINGS Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. CONCLUSIONS The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA. TRIAL REGISTRATION ClinicalTrials.gov NCT00211224

Articles Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial

Summary Background In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare effi cacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in coinfected patients