Showing papers by "University of Montpellier published in 2010"

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

Abstract: The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well. This abstract has been translated to other languages (File S1).

Functional diversity measures: an overview of their redundancy and their ability to discriminate community assembly rules

Abstract: Summary 1. Indices quantifying the functional aspect of biodiversity are essential in understanding relationships between biodiversity, ecosystem functioning and environmental constraints. Many indices of functional diversity have been published but we lack consensus about what indices quantify, how redundant they are and which ones are recommended. 2. This study aims to build a typology of functional diversity indices from artificial data sets encompassing various community structures (different assembly rules, various species richness levels) and to identify a set of independent indices able to discriminate community assembly rules. 3. Our results confirm that indices can be divided into three main categories, each of these corresponding to one aspect of functional diversity: functional richness, functional evenness and functional divergence. Most published indices are highly correlated and quantify functional richness while quadratic entropy (Q) represents a mix between functional richness and functional divergence. Conversely, two indices (FEve and FDiv respectively quantifying functional evenness and functional divergence) are rather independent to all the others. The power analysis revealed that some indices efficiently detect assembly rules while others performed poorly. 4. To accurately assess functional diversity and establish its relationships with ecosystem functioning and environmental constraints, we recommend investigating each functional component separately with the appropriate index. Guidelines are provided to help choosing appropriate indices given the issue being investigated. 5. This study demonstrates that functional diversity indices have the potential to reveal the processes that structure biological communities. Combined with complementary methods (phylogenetic and taxonomic diversity), the multifaceted framework of functional diversity will help improve our understanding of how biodiversity interacts with ecosystem processes and environmental constraints.

Proximal Alternating Minimization and Projection Methods for Nonconvex Problems: An Approach Based on the Kurdyka-Łojasiewicz Inequality

Abstract: We study the convergence properties of an alternating proximal minimization algorithm for nonconvex structured functions of the type: L(x,y)=f(x)+Q(x,y)+g(y), where f and g are proper lower semicontinuous functions, defined on Euclidean spaces, and Q is a smooth function that couples the variables x and y. The algorithm can be viewed as a proximal regularization of the usual Gauss-Seidel method to minimize L. We work in a nonconvex setting, just assuming that the function L satisfies the Kurdyka-Łojasiewicz inequality. An entire section illustrates the relevancy of such an assumption by giving examples ranging from semialgebraic geometry to “metrically regular” problems. Our main result can be stated as follows: If L has the Kurdyka-Łojasiewicz property, then each bounded sequence generated by the algorithm converges to a critical point of L. This result is completed by the study of the convergence rate of the algorithm, which depends on the geometrical properties of the function L around its critical points. When specialized to $Q(x,y)=\Vert x-y \Vert ^2$ and to f, g indicator functions, the algorithm is an alternating projection mehod (a variant of von Neumann's) that converges for a wide class of sets including semialgebraic and tame sets, transverse smooth manifolds or sets with “regular” intersection. To illustrate our results with concrete problems, we provide a convergent proximal reweighted l1 algorithm for compressive sensing and an application to rank reduction problems.

C-H bond activation in transition metal species from a computational perspective

Abstract: ion step. The reactivity of pMMO has been also explored by Chan,525 by means of DFT calculations on small models of Figure 116. Nonradical mechanism proposed in the Yoshizawa model of sMMO. Figure 117. Mononuclear and dinuclear models of the copper active sites of pMMO. CsH Bond Activation in Transition Metal Species Chemical Reviews, 2010, Vol. 110, No. 2 813

Spatial mismatch and congruence between taxonomic, phylogenetic and functional diversity: the need for integrative conservation strategies in a changing world

Abstract: Functional and phylogenetic diversity are increasingly quantified in various fields of ecology and conservation biology. The need to maintain diversity turnover among sites, so-called beta-diversity, has also been raised in theoretical and applied ecology. In this study, we propose the first comprehensive framework for the large-scale mapping of taxonomic, phylogenetic and functional diversity and of their respective turnover. Using high-resolution data on the spatial distribution and abundance of birds at a country scale, we disentangled areas of mismatches and congruencies between biodiversity components. We further revealed unequal representation of each component in protected areas: functional diversity was significantly under-represented whereas taxonomic diversity was significantly over-represented in protected areas. Our results challenge the use of any one diversity component as a surrogate for other components and stress the need to adopt an integrative approach to biodiversity conservation.

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

Abstract: The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches."

Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization Consultation on Severe Asthma

Abstract: Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as "Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)." Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment.

Adaptation genomics: the next generation.

Abstract: Understanding the genetics of how organisms adapt to changing environments is a fundamental topic in modern evolutionary ecology. The field is currently progressing rapidly because of advances in genomics technologies, especially DNA sequencing. The aim of this review is to first briefly summarise how next generation sequencing (NGS) has transformed our ability to identify the genes underpinning adaptation. We then demonstrate how the application of these genomic tools to ecological model species means that we can start addressing some of the questions that have puzzled ecological geneticists for decades such as: How many genes are involved in adaptation? What types of genetic variation are responsible for adaptation? Does adaptation utilise pre-existing genetic variation or does it require new mutations to arise following an environmental change?

Defining and measuring ecological specialization

Abstract: Summary 1. Ecological specialization is one of the main concepts in ecology and conservation. However, this concept has become highly context-dependent and is now obscured by the great variability of existing definitions and methods used to characterize ecological specialization. 2. In this study, we clarify this concept by reviewing the strengths and limitations of different approaches commonly used to define and measure ecological specialization. We first show that ecological specialization can either be considered as reflecting species’ requirements or species’ impacts. We then explain how specialization depends on species-specific characteristics and on local and contingent environmental constraints. We further show why and how ecological specialization should be scaled across spatial and temporal scales, and from individuals to communities. 3. We then illustrate how this review can be used as a practical toolbox to classify widely used metrics of ecological specialization in applied ecology, depending on the question being addressed, the method used, and the data available. 4. Synthesis and applications. Clarifying ecological specialization is useful to make explicit connections between several fields of ecology using the niche concept. Defining this concept and its practical metrics is also a crucial step to better formulate predictions of scientific interest in ecology and conservation. Finally, understanding the different facets of ecological specialization should facilitate to investigate the causes and consequences of biotic homogenization and to derive relevant indicators of biodiversity responses to land-use changes.

Contrasting changes in taxonomic vs. functional diversity of tropical fish communities after habitat degradation.

Abstract: Human activities have strong impacts on ecosystem functioning through their effect on abiotic factors and on biodiversity. There is also growing evidence that species functional traits link changes in species composition and shifts in ecosystem processes. Hence, it appears to be of utmost importance to quantify modifications in the functional structure of species communities after human disturbance in addition to changes in taxonomic structure. Despite this fact, there is still little consensus on the actual impacts of human-mediated habitat alteration on the components of biodiversity, which include species functional traits. Therefore, we studied changes in taxonomic diversity (richness and evenness), in functional diversity, and in functional specialization of estuarine fish communities facing drastic environmental and habitat alterations. The Terminos Lagoon (Gulf of Mexico) is a tropical estuary of primary concern for its biodiversity, its habitats, and its resource supply, which have been severely impacted by human activities. Fish communities were sampled in four zones of the Terminos Lagoon 18 years apart (1980 and 1998). Two functions performed by fish (food acquisition and locomotion) were studied through the measurement of 16 functional traits. Functional diversity of fish communities was quantified using three independent components: richness, evenness, and divergence. Additionally, we measured the degree of functional specialization in fish communities. We used a null model to compare the functional and the taxonomic structure of fish communities between 1980 and 1998. Among the four largest zones studied, three did not show strong functional changes. In the northern part of the lagoon, we found an increase in fish richness but a significant decrease of functional divergence and functional specialization. We explain this result by a decline of specialized species (i.e., those with particular combinations of traits), while newly occurring species are redundant with those already present. The species that decreased in abundance have functional traits linked to seagrass habitats that regressed consecutively to increasing eutrophication. The paradox found in our study highlights the need for a multifaceted approach in the assessment of biodiversity changes in communities under pressure.

Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications

Abstract: Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that are isolated from many adult tissues, in particular from the bone marrow and adipose tissue. Along with their capacity for differentiating into cells of mesodermal lineage, such as adipocytes, osteoblasts and chondrocytes, these cells have also generated great interest for their ability to display immunomodulatory capacities. Indeed, a major breakthrough came with the finding that they are able to induce peripheral tolerance, suggesting they may be used as therapeutic tools in immune-mediated disorders. The present review aims at discussing the current knowledge on the targets and mechanisms of MSC-mediated immunosuppression as well as the potential use of MSCs as modulators of immune responses in a variety of diseases related to alloreactive immunity or autoimmunity

Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo

Abstract: Small RNAs of the piRNA (Piwi-associated RNA) class have various functions in the germline — repressing transposable elements, maintaining germline stem cells and promoting genome stability. Rouget et al. have now uncovered a function for piRNAs outside the germline, in the fruit fly embryo. Specifically, piRNAs that are complementary to a sequence in the 3′-untranslated region of an mRNA for the embryonic posterior morphogen Nanos facilitate adenylation of the mRNA and its subsequent decay. Without piRNAs, Nanos accumulates and developmental defects result. Piwi-associated RNAs (piRNAs) are small RNAs with several functions in the germline, such as repressing transposable elements and helping to maintain germline stem cells. Now, a function for piRNAs has been discovered outside the germline, in the fruitfly embryo. Specifically, piRNAs are required for the decay of the messenger RNA encoding the posterior morphogen Nanos. When piRNA-induced regulation is impaired, this mRNA is stabilized and developmental defects ensue. Piwi-associated RNAs (piRNAs), a specific class of 24- to 30-nucleotide-long RNAs produced by the Piwi-type of Argonaute proteins, have a specific germline function in repressing transposable elements. This repression is thought to involve heterochromatin formation and transcriptional and post-transcriptional silencing1,2,3,4,5,6. The piRNA pathway has other essential functions in germline stem cell maintenance7 and in maintaining germline DNA integrity8,9,10. Here we uncover an unexpected function of the piRNA pathway in the decay of maternal messenger RNAs and in translational repression in the early embryo. A subset of maternal mRNAs is degraded in the embryo at the maternal-to-zygotic transition. In Drosophila, maternal mRNA degradation depends on the RNA-binding protein Smaug and the deadenylase CCR411,12,13, as well as the zygotic expression of a microRNA cluster14. Using mRNA encoding the embryonic posterior morphogen Nanos (Nos) as a paradigm to study maternal mRNA decay, we found that CCR4-mediated deadenylation of nos depends on components of the piRNA pathway including piRNAs complementary to a specific region in the nos 3′ untranslated region. Reduced deadenylation when piRNA-induced regulation is impaired correlates with nos mRNA stabilization and translational derepression in the embryo, resulting in head development defects. Aubergine, one of the Argonaute proteins in the piRNA pathway, is present in a complex with Smaug, CCR4, nos mRNA and piRNAs that target the nos 3′ untranslated region, in the bulk of the embryo. We propose that piRNAs and their associated proteins act together with Smaug to recruit the CCR4 deadenylation complex to specific mRNAs, thus promoting their decay. Because the piRNAs involved in this regulation are produced from transposable elements, this identifies a direct developmental function for transposable elements in the regulation of gene expression.

The metal-poor end of the Spite plateau - I. Stellar parameters, metallicities, and lithium abundances

Abstract: Context. The primordial nature of the Spite plateau is at odds with the WMAP satellite measurements, implying a primordial Li production at least three times higher than observed. It has also been suggested that A (Li) might exhibit a positive correlation with metallicity below [Fe/H] ~ −2.5. Previous samples studied comprised few stars below [Fe/H] = −3.Aims. We present VLT-UVES Li abundances of 28 halo dwarf stars between [Fe/H] = −2.5 and −3.5, ten of which have [Fe/H] We determined stellar parameters and abundances using four different T eff scales. The direct infrared flux method was applied to infrared photometry. Hα wings were fitted with two synthetic grids computed by means of 1D LTE atmosphere models, assuming two different self-broadening theories. A grid of Hα profiles was finally computed by means of 3D hydrodynamical atmosphere models. The Li i doublet at 670.8 nm has been used to measure A (Li) by means of 3D hydrodynamical NLTE spectral syntheses. An analytical fit of A (Li)3D,NLTE as a function of equivalent width, T eff , log g , and [Fe/H] has been derived and is made available.Results. We confirm previous claims that A (Li) does not exhibit a plateau below [Fe/H] = −3. We detect a strong positive correlation with [Fe/H] that is insensitive to the choice of T eff estimator. From a linear fit, we infer a steep slope of about 0.30 dex in A (Li) per dex in [Fe/H], which has a significance of 2–3σ . The slopes derived using the four T eff estimators are consistent to within 1σ . A significant slope is also detected in the A (Li)–T eff plane, driven mainly by the coolest stars in the sample (T eff (Li)–[Fe/H] plane is not altered significantly. When the full sample is considered, the scatter in A (Li) increases by a factor of 2 towards lower metallicities, while the plateau appears very thin above [Fe/H] = −2.8. At this metallicity, the plateau lies at $\rm\left\langle{{\it A}(Li)_{3D,NLTE}}\right\rangle=2.199\pm0.086$A(Li)3D,NLTE=2.199±0.086. Conclusions. The meltdown of the Spite plateau below [Fe/H] ~ −3 is established, but its cause is unclear. If the primordial A (Li) were that derived from standard BBN, it appears difficult to envision a single depletion phenomenon producing a thin, metallicity independent plateau above [Fe/H] = −2.8, and a highly scattered, metallicity dependent distribution below. That no star below [Fe/H] = −3 lies above the plateau suggests that they formed at plateau level and experienced subsequent depletion.

Nestedness versus modularity in ecological networks: two sides of the same coin?

Abstract: 1. Understanding the structure of ecological networks is a crucial task for interpreting community and ecosystem responses to global change. 2. Despite the recent interest in this subject, almost all studies have focused exclusively on one specific network property. The question remains as to what extent different network properties are related and how understanding this relationship can advance our comprehension of the mechanisms behind these patterns. 3. Here, we analysed the relationship between nestedness and modularity, two frequently studied network properties, for a large data set of 95 ecological communities including both plant-animal mutualistic and host-parasite networks. 4. We found that the correlation between nestedness and modularity for a population of random matrices generated from the real communities decreases significantly in magnitude and sign with increasing connectance independent of the network type. At low connectivities, networks that are highly nested also tend to be highly modular; the reverse happens at high connectivities. 5. The above result is qualitatively robust when different null models are used to infer network structure, but, at a finer scale, quantitative differences exist. We observed an important interaction between the network structure pattern and the null model used to detect it. 6. A better understanding of the relationship between nestedness and modularity is important given their potential implications on the dynamics and stability of ecological communities.

Fermi observations of GRB 090510 : A short-hard gamma-ray burst with an additional, hard power-law component from 10 keV to GeV energies

Abstract: We present detailed observations of the bright short-hard gamma-ray burst GRB 090510 made with the Gammaray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi observatory. GRB 090510 is the first burst detected by the LAT that shows strong evidence for a deviation from a Band spectral fitting function during the prompt emission phase. The time-integrated spectrum is fit by the sum of a Band function with E-peak = 3.9 +/- 0.3 MeV, which is the highest yet measured, and a hard power-law component with photon index -1.62 +/- 0.03 that dominates the emission below approximate to 20 keV and above approximate to 100 MeV. The onset of the high-energy spectral component appears to be delayed by similar to 0.1 s with respect to the onset of a component well fit with a single Band function. A faint GBM pulse and a LAT photon are detected 0.5 s before the main pulse. During the prompt phase, the LAT detected a photon with energy 30.5(-2.6)(+5.8) GeV, the highest ever measured from a short GRB. Observation of this photon sets a minimum bulk outflow Lorentz factor, Gamma greater than or similar to 1200, using simple.. opacity arguments for this GRB at redshift z = 0.903 and a variability timescale on the order of tens of ms for the approximate to 100 keV-few MeV flux. Stricter high confidence estimates imply Gamma greater than or similar to 1000 and still require that the outflows powering short GRBs are at least as highly relativistic as those of long-duration GRBs. Implications of the temporal behavior and power-law shape of the additional component on synchrotron/synchrotron self-Compton, external-shock synchrotron, and hadronic models are considered.

Gamma-ray light curves and variability of bright fermi-detected blazars

Abstract: This paper presents light curves as well as the first systematic characterization of variability of the 106 objects in the high-confidence Fermi Large Area Telescope Bright AGN Sample (LBAS) Weekly light curves of this sample, obtained during the first 11 months of the Fermi survey (2008 August 4–2009 July 4), are tested for variability and their properties are quantified through autocorrelation function and structure function analysis For the brightest sources, 3 or 4 day binned light curves are extracted in order to determine power density spectra (PDSs) and to fit the temporal structure of major flares More than 50% of the sources are found to be variable with high significance, where high states do not exceed 1/4 of the total observation range Variation amplitudes are larger for flat spectrum radio quasars and low/intermediate synchrotron frequency peaked BL Lac objects Autocorrelation timescales derived from weekly light curves vary from four to a dozen of weeks Variable sources of the sample have weekly and 3–4 day bin light curves that can be described by 1/f α PDS, and show two kinds of gamma-ray variability: (1) rather constant baseline with sporadic flaring activity characterized by flatter PDS slopes resembling flickering and red noise with occasional intermittence and (2)—measured for a few blazars showing strong activity—complex and structured temporal profiles characterized by long-term memory and steeper PDS slopes, reflecting a random walk underlying mechanism The average slope of the PDS of the brightest 22 FSRQs and of the 6 brightest BL Lacs is 15 and 17, respectively The study of temporal profiles of well-resolved flares observed in the 10 brightest LBAS sources shows that they generally have symmetric profiles and that their total duration vary between 10 and 100 days Results presented here can assist in source class recognition for unidentified sources and can serve as reference for more detailed analysis of the brightest gamma-ray blazars

The differing and mediating roles of trust and relationship commitment in service relationship maintenance and development

Abstract: Relationship maintenance (customer retention and exclusivity) and development (increased service usage and cross-buying) are top priorities in Customer Relationship Management. This paper examines how service companies can effectively influence customer patronage behaviors by leveraging overall customer satisfaction, trust and relationship commitment. Using a longitudinal design over a two-year period, we merge survey metrics with actual patronage behaviors taken from a bank’s database. We show that relationship commitment just enhances retention and exclusivity while trust directly influences service usage and cross-buying. As a consequence, trust appears to be highly critical for service relationship development and company profits. Furthermore, trust and relationship commitment mediate the entire impact of satisfaction which appears as a necessary but not sufficient condition for relationship maintenance and development. Satisfaction, and more generally service evaluations, must be efficiently converted into trust and relationship commitment before providing business results. Finally, we establish the temporal antecedence and the predictive power of trust and relationship commitment. Relationship commitment in year t predicts the number of service providers in year t + 1 (exclusivity vs. polygamy), while trust in year t predicts the number of bank products (cross-buying) as well as the service usage level in year t + 1. We then discuss managerial implications for customer relationship maintenance and development.

An intervention to decrease complications related to endotracheal intubation in the intensive care unit: a prospective, multiple-center study.

Abstract: To determined whether the implementation of an intubation management protocol leads to the reduction of intubation-related complications in the intensive care unit (ICU). Two-phase, prospective, multicenter controlled study. Three medical-surgical ICUs in two university hospitals. Two hundred three consecutive ICU patients required 244 intubations. All intubations performed during two consecutive phases (a 6-month quality control phase followed by a 6-month intervention phase based on the implementation of an ICU intubation bundle management protocol) were evaluated. The ten bundle components were: preoxygenation with noninvasive positive pressure ventilation, presence of two operators, rapid sequence induction, cricoid pressure, capnography, protective ventilation, fluid loading, preparation and early administration of sedation and vasopressor use if needed. The primary end points were the incidence of life-threatening complications occurring within 60 min after intubation (cardiac arrest or death, severe cardiovascular collapse and hypoxemia). Other complications (mild to moderate) were also evaluated. Baseline characteristics, including demographic data and reason for intubation (mainly acute respiratory failure), were similar in the two phases. The intubation procedure in the intervention phase (n = 121) was associated with significant decreases in both life-threatening complications (21 vs. 34%, p = 0.03) and other complications (9 vs. 21%, p = 0.01) compared to the control phase (n = 123). The implementation of an intubation management protocol can reduce immediate severe life-threatening complications associated with intubation of ICU patients.

Multi-system neurological disease is common in patients with OPA1 mutations

Abstract: Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal 'dominant optic atrophy plus' variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

The metal-poor end of the Spite plateau. 1: Stellar parameters, metallicities and lithium abundances

Abstract: We present VLT-UVES Li abundances for 28 halo dwarf stars between [Fe/H]=-2.5 and -3.5, 10 of which have [Fe/H]<-3. Four different T_eff scales have been used. Direct Infrared Flux Method (IRFM) has been used on the basis of 2MASS infrared photometry. H_alpha wings have been fitted against synthetic grids computed by means of 1D LTE atmosphere models, assuming different self-broadening theories. Finally, a grid of H_alpha profiles has been computed by means of 3D hydrodynamical atmosphere models. The Li I doublet at 670.8 nm has been used to measure A(Li) by means of 3D hydrodynamical NLTE spectral syntheses. An analytical fit of A(Li)(3D, NLTE) as a function of equivalent width, T_eff, log g, and [Fe/H] has been derived and is made available. A(Li) does not exhibit a plateau below [Fe/H]=-3. A strong positive correlation with [Fe/H] appears, not influenced by the choice of the T_eff estimator. From a linear fit, we obtain a strong slope of about 0.30 dex in A(Li) per dex in [Fe/H], significant to 2-3 sigma, and consistent among all the four T_eff estimators. A significant slope is also detected in the A(Li)--T_eff plane, driven mainly by the coolest stars in the sample which appear Li-poor. Removing such stars does not alter the behavior in the A(Li)-[Fe/H] plane. The scatter in A(Li) increases by a factor of 2 towards lower metallicities, while the plateau appears very thin above [Fe/H]=-2.8. The meltdown of the Spite plateau below [Fe/H]\sim-3 is established, but its cause is unclear. If the primordial A(Li) is the one derived from WMAP, it appears difficult to envision a single depletion phenomenon producing a thin, metallicity independent plateau above [Fe/H]=-2.8, and a highly scattered, metallicity dependent distribution below. The fact that no star below [Fe/H]=-3 lies above the plateau suggests that they formed at plateau level and underwent subsequent depletion.

Insecticide control of vector-borne diseases: when is insecticide resistance a problem?

Abstract: Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way-and there may be no simple generality-the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention.

Heterozygosity-fitness correlations: a time for reappraisal.

Abstract: Owing to the remarkable progress of molecular techniques, heterozygosity-fitness correlations (HFCs) have become a popular tool to study the impact of inbreeding in natural populations However, their underlying mechanisms are often hotly debated Here we argue that these "debates" rely on verbal arguments with no basis in existing theory and inappropriate statistical testing, and that it is time to reconcile HFC with its historical and theoretical fundaments We show that available data are quantitatively and qualitatively consistent with inbreeding-based theory HFC can be used to estimate the impact of inbreeding in populations, although such estimates are bound to be imprecise, especially when inbreeding is weak Contrary to common belief, linkage disequilibrium is not an alternative to inbreeding, but rather comes with some forms of inbreeding, and is not restricted to closely linked loci Finally, the contribution of local chromosomal effects to HFC, while predicted by inbreeding theory, is expected to be small, and has rarely if ever proven statistically significant using adequate tests We provide guidelines to safely interpret and quantify HFCs, and present how HFCs can be used to quantify inbreeding load and unravel the structure of natural populations

A Short‐Term, Randomized, Double‐Blind, Parallel‐Group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS Study

Abstract: Dronedarone versus Amiodarone in Patients with AF. Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone-napatients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardiover- sion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio (HR) 1.59; 95% confi- dence interval (CI) 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. (J Cardiovasc Electrophysiol, Vol. pp. 1-9)