Susceptibility to exacerbation in chronic obstructive pulmonary disease

Background Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. Methods We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End points (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both)or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Results Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient"s recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Conclusions Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials .gov number, NCT00292552.)

Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.

Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.

Prolonged fluconazole exposure leads to a shift to Candida species with decreased susceptibility in breakthrough candidemia: prospective survey of the Fungal Infection Network of Switzerland

Objectives: To compare the clinical characteristics, species distribution and antifungal susceptibility of Candida bloodstream isolates (BSI) in breakthrough (BTC) vs. non-breakthrough candidemia (NBTC) and to study the effect of prolonged vs. short fluconazole (F) exposure in BTC.Methods: Candida BSI were prospectively collected during 2004- 2006 from 27 hospitals (seven university, 20 affiliated) of the FUNGINOS network. Susceptibility to F, voriconazole (V) and caspofungin (C) was tested in the FUNGINOS mycology reference laboratory by microtitre broth dilution method with the Sensititre YeastOneTM test panel. Clinical data were collected using standardized CRFs. BTC was defined as occurring during antifungal treatment/prophylaxis of at least three days duration prior to the candidemia. Susceptibility of BSI was defined according to 2010/2011 CLSI clinical breakpoints.Results: Out of 567 candidemia episodes, 550 Candida BSI were available. Of these, 43 (7.6%) were from BTC (37/43, 86% were isolated after F exposure). 38 BTC (88.4%) and 315 NBTC (55.6%) occurred in university hospitals (P < 0.001). The majority of patients developing BTC were immunocompromised: higher proportions of haematological malignancies (62.8% in BTC vs. 47.1% in NBTC, P < 0.001), neutropenia (37.2% vs. 11.8%, P < 0.001), acute GvHD (14% vs. 0.2%, P < 0.001), immunosuppressive drugs (74.4% vs. 7.8%, P < 0.001), and mucositis (32.6% vs. 2.3%, P < 0.001) were observed. Other differences between BTC and NBTC were higher proportions of patients with central venous catheters in the 2 weeks preceding candidemia (95.3% vs. 83.4%, P = 0.047) and receiving total parenteral nutrition (62.8% vs. 35.9%, P < 0.001), but a lower proportion of patients treated with gastric proton pump inhibitors (23.3% vs. 72.1%, P < 0.001). Overall mortality of BTC and NBTC was not different (34.9% vs. 31.7%, P = 0.73), while a trend to higher attributable mortality in BTC was found (13.9% vs. 6.9%, P = 0.12). Species identification showed a majority of C. albicans in both groups (51.2% in BTC vs. 62.9% in NBTC, P = 0.26), followed by C. glabrata (18.6% vs. 18.5%), C. tropicalis (2.3% vs. 6.3%) and C. parapsilosis (7.0% vs. 4.7%). Significantly more C. krusei were detected in BTC versus NBTC (11.6% vs. 1.6%, P = 0.002). The geometric mean MIC for F, V and C between BTC and NBTC isolates was not significantly different. However, in BTC there was a significant association between duration of F exposure and the Candida spp.: >10 days of F was associated with a significant shift from susceptible Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, C. famata) to non-susceptible species (C. glabrata, C. krusei, C. norvegensis). Among 21 BTC episodes occurring after £10 days of F, 19% of the isolates were non-susceptible, in contrast to 68.7% in 16 BTC episodes occurring after >10 days of F (P = 0.003).Conclusions: Breakthrough candidemia occurred more often in immunocompromised hosts. Fluconazole administered for >10 days was associated with a shift to non-susceptible Candida spp.. Length of fluconazole exposure should be taken into consideration for the choice of empirical antifungal treatment.

Developmental regulation of expression of schizophrenia susceptibility genes in the primate hippocampal formation

The hippocampal formation is essential for normal memory function and is implicated in many neurodevelopmental, neurodegenerative and neuropsychiatric disorders. In particular, abnormalities in hippocampal structure and function have been identified in schizophrenic subjects. Schizophrenia has a strong polygenic component, but the role of numerous susceptibility genes in normal brain development and function has yet to be investigated. Here we described the expression of schizophrenia susceptibility genes in distinct regions of the monkey hippocampal formation during early postnatal development. We found that, as compared with other genes, schizophrenia susceptibility genes exhibit a differential regulation of expression in the dentate gyrus, CA3 and CA1, over the course of postnatal development. A number of these genes involved in synaptic transmission and dendritic morphology exhibit a developmental decrease of expression in CA3. Abnormal CA3 synaptic organization observed in schizophrenics might be related to some specific symptoms, such as loosening of association. Interestingly, changes in gene expression in CA3 might occur at a time possibly corresponding to the late appearance of the first clinical symptoms. We also found earlier changes in expression of schizophrenia susceptibility genes in CA1, which might be linked to prodromal psychotic symptoms. A number of schizophrenia susceptibility genes including APOE, BDNF, MTHFR and SLC6A4 are involved in other disorders, and thus likely contribute to nonspecific changes in hippocampal structure and function that must be combined with the dysregulation of other genes in order to lead to schizophrenia pathogenesis.

European genetic diversity and susceptibility to pathogens.

Infectious diseases, both in their endemic and epidemic forms, have shaped the human genome. Ecology has also contributed to geographically constrained pressures on human populations. There are now multiple examples of population-specific genetic variants that modulate susceptibility to infection - several of which have been observed solely in Europeans. The pathogen genome also mutates and adapts to individuals and common alleles in populations. The current understanding has benefited from genome-wide association studies as well as from rapid progress in the genetic characterization of Mendelian immunodeficiencies that are defined by susceptibility to specific pathogens. It is expected that current efforts to characterize rare human genetic variants will contribute to the understanding of severe manifestations of common infections in European and other human groups.

Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB / c mice.

Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.

Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene.

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Genes outside The Hla Region affecting Susceptibility to Type 1 Diabetes - The Role of Iddm2 and Iddm9 in the Finnish Population

Tyypin 1 diabeteksen perinnöllinen alttius Suomessa - HLA-alueen ulkopuolisten alttiuslokusten IDDM2 ja IDDM9 rooli taudin periytymisessä HLA-alue, joka sijaitsee kromosomissa 6p21.3, vastaa noin puolesta perinnöllisestä alttiudesta sairastua tyypin 1 diabetekseen. Myös HLA-alueen ulkopuolisten lokusten on todettu liittyvän sairausalttiuteen. Näistä kolmen lokuksen on varmistettu olevan todellisia alttiuslokuksia ja lisäksi useiden muiden, vielä varmistamattomien lokusten, on todettu liittyvän sairausalttiuteen. Tässä tutkimuksessa 12:n HLA-alueen ulkopuolisen alttiuslokuksen kytkentä tyypin 1 diabetekseen tutkittiin käyttäen 107:aa suomalaista multiplex-perhettä. Jatkotutkimuksessa analysoitiin IDDM9-alueen kytkentä ja assosiaatio sairauteen laajennetuissa perhemateriaaleissa sekä IDDM2-alueen mahdollinen interaktio HLA-alueen kanssa sairauden muodostumisessa. Lisäksi suoritettiin IDDM2-alueen suojaavien haplotyyppien alatyypitys tarkoituksena tutkia eri haplotyyppien käyttökelpoisuutta sairastumisriskin tarkempaa ennustamista varten. Ensimmäisessä kytkentätutkimuksessa ei löytynyt koko genomin tasolla merkitsevää tai viitteellistä kytkentää tutkituista HLA-alueen ulkopuolisista lokuksista. Voimakkain havaittu nimellisen merkitsevyyden tavoittava kytkentä nähtiin IDDM9-alueen markkerilla D3S3576 (MLS=1.05). Tutkimuksessa ei kyetty varmistamaan tai sulkemaan pois aiempia kytkentähavaintoja tutkituilla lokuksilla, mutta IDDM9-alueen jatkotutkimuksessa havaittu voimakas kytkentä (MLS=3.4) ja merkitsevä assosiaatio (TDT p=0.0002) viittaa vahvasti siihen, että 3q21-alueella sijaitsee todellinen tyypin 1 diabeteksen alttiusgeeni, jolloin alueen kattava assosiaatiotutkimus olisi perusteltu jatkotoimenpide. Sairauteen altistava IDDM2-alueen MspI-2221 genotyyppi CC oli nimellisesti yleisempi matalan tai kohtalaisen HLA-sairastumisriskin diabeetikoilla, verrattuna korkean HLA-riskin potilaisiin (p=0.05). Myös genotyyppijakauman vertailu osoitti merkitsevää eroa ryhmien välillä (p=0.01). VNTR-haplotyyppitutkimus osoitti, että IIIA/IIIA-homotsygootin sairaudelta suojaava vaikutus on merkitsevästi voimakkaampi kuin muiden luokka III:n genotyypeillä. Nämä tulokset viittaavat IDDM2-HLA -vuorovaikutukseen sekä siihen että IDDM2-alueen haplotyyppien välillä esiintyy etiologista heterogeniaa. Tämän johdosta IDDM2-alueen haplotyyppien tarkempi määrittäminen voisi tehostaa tyypin 1 diabeteksen riskiarviointia.

Antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin-positive meticillin-resistant Staphylococcus aureus: An international survey

The antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) isolates reported from 17 countries in the Americas, Europe and, Australia-Asia were analysed. Among a total of 3236 non-duplicate isolates, the lowest susceptibility was observed to erythromycin in all regions. Susceptibility to ciprofloxacin showed large variation (25%, 75% and 84% in the Americas, Europe and Australia-Asia, respectively). Two vancomycin-intermediate PVL-positive MRSA isolates were reported, one from Hong Kong and the other from The Netherlands. Resistance to trimethoprim/sulfamethoxazole and linezolid was <1%. Among 1798 MRSA isolates from 13 countries that were tested for the requested 10 non-β-lactam antibiotics, 49.4% were multisusceptible. However, multiresistant isolates (resistant to at least three classes of non-β-lactam antibiotics) were reported from all regions. Sequence type 30 (ST30) was reported worldwide, whereas ST80 and ST93 were exclusive to Europe and Australia, respectively. USA300 and related clones (ST8) are progressively replacing the ST80 clone in several European countries. Eight major clusters were discriminated by multilocus variable-number tandem repeat assay (MLVA), showing a certain geographic specificity. PVL-positive MRSA isolates frequently remain multisusceptible to non-β-lactam agents, but multiresistance is already prevalent in all regions. Surveillance of MRSA susceptibility patterns should be monitored to provide clinicians with the most current information regarding changes in resistance patterns.

In vivo effect of flucloxacillin in experimental endocarditis caused by mecC-positive staphylococcus aureus showing temperature-dependent susceptibility in vitro.

Methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene (mecC-MRSA) exhibited at 37°C MICs of oxacillin close to those of methicillin-susceptible S. aureus (MSSA). We investigated whether at this temperature, mecC-MRSA strains respond to flucloxacillin treatment like MSSA strains, using a rat model of endocarditis. Flucloxacillin (human-like kinetics of 2 g intravenously every 6 h) cured 80 to 100% of aortic vegetations infected with five different mecC-MRSA strains. These results suggest that mecC-MRSA infections may successfully respond to treatment with β-lactams.

Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens.

The animal gut plays a central role in tackling two common ecological challenges, nutrient shortage and food-borne parasites, the former by efficient digestion and nutrient absorption, the latter by acting as an immune organ and a barrier. It remains unknown whether these functions can be independently optimised by evolution, or whether they interfere with each other. We report that Drosophila melanogaster populations adapted during 160 generations of experimental evolution to chronic larval malnutrition became more susceptible to intestinal infection with the opportunistic bacterial pathogen Pseudomonas entomophila. However, they do not show suppressed immune response or higher bacterial loads. Rather, their increased susceptibility to P. entomophila is largely mediated by an elevated predisposition to loss of intestinal barrier integrity upon infection. These results may reflect a trade-off between the efficiency of nutrient extraction from poor food and the protective function of the gut, in particular its tolerance to pathogen-induced damage.

Rockfall susceptibility assessment and remote geological mapping with LiDAR point clouds

Characterizing the geological features and structures in three dimensions over inaccessible rock cliffs is needed to assess natural hazards such as rockfalls and rockslides and also to perform investigations aimed at mapping geological contacts and building stratigraphy and fold models. Indeed, the detailed 3D data, such as LiDAR point clouds, allow to study accurately the hazard processes and the structure of geologic features, in particular in vertical and overhanging rock slopes. Thus, 3D geological models have a great potential of being applied to a wide range of geological investigations both in research and applied geology projects, such as mines, tunnels and reservoirs. Recent development of ground-based remote sensing techniques (LiDAR, photogrammetry and multispectral / hyperspectral images) are revolutionizing the acquisition of morphological and geological information. As a consequence, there is a great potential for improving the modeling of geological bodies as well as failure mechanisms and stability conditions by integrating detailed remote data. During the past ten years several large rockfall events occurred along important transportation corridors where millions of people travel every year (Switzerland: Gotthard motorway and railway; Canada: Sea to sky highway between Vancouver and Whistler). These events show that there is still a lack of knowledge concerning the detection of potential rockfalls, making mountain residential settlements and roads highly risky. It is necessary to understand the main factors that destabilize rocky outcrops even if inventories are lacking and if no clear morphological evidences of rockfall activity are observed. In order to increase the possibilities of forecasting potential future landslides, it is crucial to understand the evolution of rock slope stability. Defining the areas theoretically most prone to rockfalls can be particularly useful to simulate trajectory profiles and to generate hazard maps, which are the basis for land use planning in mountainous regions. The most important questions to address in order to assess rockfall hazard are: Where are the most probable sources for future rockfalls located? What are the frequencies of occurrence of these rockfalls? I characterized the fracturing patterns in the field and with LiDAR point clouds. Afterwards, I developed a model to compute the failure mechanisms on terrestrial point clouds in order to assess the susceptibility to rockfalls at the cliff scale. Similar procedures were already available to evaluate the susceptibility to rockfalls based on aerial digital elevation models. This new model gives the possibility to detect the most susceptible rockfall sources with unprecented detail in the vertical and overhanging areas. The results of the computation of the most probable rockfall source areas in granitic cliffs of Yosemite Valley and Mont-Blanc massif were then compared to the inventoried rockfall events to validate the calculation methods. Yosemite Valley was chosen as a test area because it has a particularly strong rockfall activity (about one rockfall every week) which leads to a high rockfall hazard. The west face of the Dru was also chosen for the relevant rockfall activity and especially because it was affected by some of the largest rockfalls that occurred in the Alps during the last 10 years. Moreover, both areas were suitable because of their huge vertical and overhanging cliffs that are difficult to study with classical methods. Limit equilibrium models have been applied to several case studies to evaluate the effects of different parameters on the stability of rockslope areas. The impact of the degradation of rockbridges on the stability of large compartments in the west face of the Dru was assessed using finite element modeling. In particular I conducted a back-analysis of the large rockfall event of 2005 (265'000 m3) by integrating field observations of joint conditions, characteristics of fracturing pattern and results of geomechanical tests on the intact rock. These analyses improved our understanding of the factors that influence the stability of rock compartments and were used to define the most probable future rockfall volumes at the Dru. Terrestrial laser scanning point clouds were also successfully employed to perform geological mapping in 3D, using the intensity of the backscattered signal. Another technique to obtain vertical geological maps is combining triangulated TLS mesh with 2D geological maps. At El Capitan (Yosemite Valley) we built a georeferenced vertical map of the main plutonio rocks that was used to investigate the reasons for preferential rockwall retreat rate. Additional efforts to characterize the erosion rate were made at Monte Generoso (Ticino, southern Switzerland) where I attempted to improve the estimation of long term erosion by taking into account also the volumes of the unstable rock compartments. Eventually, the following points summarize the main out puts of my research: The new model to compute the failure mechanisms and the rockfall susceptibility with 3D point clouds allows to define accurately the most probable rockfall source areas at the cliff scale. The analysis of the rockbridges at the Dru shows the potential of integrating detailed measurements of the fractures in geomechanical models of rockmass stability. The correction of the LiDAR intensity signal gives the possibility to classify a point cloud according to the rock type and then use this information to model complex geologic structures. The integration of these results, on rockmass fracturing and composition, with existing methods can improve rockfall hazard assessments and enhance the interpretation of the evolution of steep rockslopes. -- La caractérisation de la géologie en 3D pour des parois rocheuses inaccessibles est une étape nécessaire pour évaluer les dangers naturels tels que chutes de blocs et glissements rocheux, mais aussi pour réaliser des modèles stratigraphiques ou de structures plissées. Les modèles géologiques 3D ont un grand potentiel pour être appliqués dans une vaste gamme de travaux géologiques dans le domaine de la recherche, mais aussi dans des projets appliqués comme les mines, les tunnels ou les réservoirs. Les développements récents des outils de télédétection terrestre (LiDAR, photogrammétrie et imagerie multispectrale / hyperspectrale) sont en train de révolutionner l'acquisition d'informations géomorphologiques et géologiques. Par conséquence, il y a un grand potentiel d'amélioration pour la modélisation d'objets géologiques, ainsi que des mécanismes de rupture et des conditions de stabilité, en intégrant des données détaillées acquises à distance. Pour augmenter les possibilités de prévoir les éboulements futurs, il est fondamental de comprendre l'évolution actuelle de la stabilité des parois rocheuses. Définir les zones qui sont théoriquement plus propices aux chutes de blocs peut être très utile pour simuler les trajectoires de propagation des blocs et pour réaliser des cartes de danger, qui constituent la base de l'aménagement du territoire dans les régions de montagne. Les questions plus importantes à résoudre pour estimer le danger de chutes de blocs sont : Où se situent les sources plus probables pour les chutes de blocs et éboulement futurs ? Avec quelle fréquence vont se produire ces événements ? Donc, j'ai caractérisé les réseaux de fractures sur le terrain et avec des nuages de points LiDAR. Ensuite, j'ai développé un modèle pour calculer les mécanismes de rupture directement sur les nuages de points pour pouvoir évaluer la susceptibilité au déclenchement de chutes de blocs à l'échelle de la paroi. Les zones sources de chutes de blocs les plus probables dans les parois granitiques de la vallée de Yosemite et du massif du Mont-Blanc ont été calculées et ensuite comparés aux inventaires des événements pour vérifier les méthodes. Des modèles d'équilibre limite ont été appliqués à plusieurs cas d'études pour évaluer les effets de différents paramètres sur la stabilité des parois. L'impact de la dégradation des ponts rocheux sur la stabilité de grands compartiments de roche dans la paroi ouest du Petit Dru a été évalué en utilisant la modélisation par éléments finis. En particulier j'ai analysé le grand éboulement de 2005 (265'000 m3), qui a emporté l'entier du pilier sud-ouest. Dans le modèle j'ai intégré des observations des conditions des joints, les caractéristiques du réseau de fractures et les résultats de tests géoméchaniques sur la roche intacte. Ces analyses ont amélioré l'estimation des paramètres qui influencent la stabilité des compartiments rocheux et ont servi pour définir des volumes probables pour des éboulements futurs. Les nuages de points obtenus avec le scanner laser terrestre ont été utilisés avec succès aussi pour produire des cartes géologiques en 3D, en utilisant l'intensité du signal réfléchi. Une autre technique pour obtenir des cartes géologiques des zones verticales consiste à combiner un maillage LiDAR avec une carte géologique en 2D. A El Capitan (Yosemite Valley) nous avons pu géoréferencer une carte verticale des principales roches plutoniques que j'ai utilisé ensuite pour étudier les raisons d'une érosion préférentielle de certaines zones de la paroi. D'autres efforts pour quantifier le taux d'érosion ont été effectués au Monte Generoso (Ticino, Suisse) où j'ai essayé d'améliorer l'estimation de l'érosion au long terme en prenant en compte les volumes des compartiments rocheux instables. L'intégration de ces résultats, sur la fracturation et la composition de l'amas rocheux, avec les méthodes existantes permet d'améliorer la prise en compte de l'aléa chute de pierres et éboulements et augmente les possibilités d'interprétation de l'évolution des parois rocheuses.