Magnitude and frequency: challenges for the assessment of vulnerability to geomorphic hazards

In natural hazard research, risk is defined as a function of (1) the probability of occurrence of a hazardous process, and (2) the assessment of the related extent of damage, defined by the value of elements at risk exposed and their physical vulnerability. Until now, various works have been undertaken to determine vulnerability values for objects exposed to geomorphic hazards such as mountain torrents. Yet, many studies only provide rough estimates for vulnerability values based on proxies for process intensities. However, the deduced vulnerability functions proposed in the literature show a wide range, in particular with respect to medium and high process magnitudes. In our study, we compare vulnerability functions for torrent processes derived from studies in test sites located in the Austrian Alps and in Taiwan. Based on this comparison we expose needs for future research in order to enhance mountain hazard risk management with a particular focus on the question of vulnerability on a catchment scale.

Landmark Detection for Fusion of Fundus and MRI Towards a Patient-Specific Multi-Modal Eye Model

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise e.g., Fundus photography, Optical Coherence Tomography (OCT), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The presented article’s goal is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI which was not visible before like vessels and the macula. This article’s contributions include automatic detection of the optic disc, the fovea, the optic axis and an automatic segmentation of the vitreous humor of the eye.

Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the d: a: d study.

BACKGROUND The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. CONCLUSIONS Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy

OBJECTIVES Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART. METHODS Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders. RESULTS Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29). CONCLUSIONS Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.

The role of LMX1B and PITX2 in anterior segment development and adult ocular function

Several congenital syndromes associated with anterior segment (AS) anomalies can lead to impaired vision and glaucoma, such as nail-patella syndrome (NPS), caused by mutations in the LIM homeodomain transcription factor LMX1B and Axenfeld-Rieger's syndrome (ARS), caused by mutations in the bicoid-related homeodomain transcription factor PITX2. Targeted mutations in lmx1b and pitx2 and RNA in situ analysis reveal that both genes are required for AS development and are co-expressed within the periocular mesenchyme, suggesting they participate in a shared genetic pathway. Lmx1b homozygous mutants display iris and corneal stroma hypoplasia, and defects in ciliary body formation. In contrast, pitx2 homozygous mutants exhibit a more severe phenotype: the AS chamber, corneal endothelium, and extraocular muscles (EOM) fail to develop. The absence of EOM in pitx2 mutants suggests pitx2 acts upstream of lmx1b, or that other lmx1b family members, such as lmx1a, can compensate for lmx1b function. Lmxla/lmx1b double homozygous mutants have a reduced capacity to generate EOM, implying that lmx1 gene products have a redundant function in EOM development and that lmx1 family members may act downstream of pitx2. However, analysis of pitx2 expression in the AS tissues of lmx1b mutants and reciprocal studies of lmx1b expression in pitx2 mutants indicate that these genes do not function in a simple linear pathway. Instead, lmx1b and pitx2 may regulate a shared set of downstream targets or both genes may work in parallel transcribing unique targets required for a common biological process. Ultrastructural analysis of lmx1b and pitx2 mutant corneas indicates that collagen fibrillogenesis is perturbed, revealing a common role for both genes in the deposition of extracellular matrix. Furthermore, lmx1b/pitx2 double heterozygotes develop corneal opacities not observed in single heterozygotes demonstrating that lmx1b and pitx2 genetically interact. Data suggests that defects in the basement membrane of the corneal endothelium underlie the opacities observed in double heterozygotes. Additionally, double heterozygotes develop anterior synechias that occlude the trabecular meshwork, potentially blocking aqueous humor drainage. These data suggest that lmx1b and pitx2 are responsible for ECM deposition in multiple cell types and imply that such defects may contribute to the glaucomas observed in NPS and ARS patients. ^

The function of math5 and myocilin in mammalian eye development and disease

Complex molecular events underlie vertebrate eye development and disease. The eye is composed of two major tissue types: the anterior and posterior segments. During development, the retinal progenitor cells differentiate into six neuronal and one non-neuronal cell types. These cell types later organize into the distinct laminar structure of the mature retina which occupies the posterior segment. In the developed anterior segment, both the ciliary body and trabecular meshwork regulate intraocular pressure created by the aqueous humor. The disruption in intraocular pressure can lead to a blinding condition called glaucoma. To characterize molecular mechanisms governing retinal development and glaucoma, two separate mouse knockout lines carrying mutations in math5 and myocilin were subjected to a series of in vivo analyses. ^ Math5 is a murine homologue of Drosophila atonal , a bHLH proneural gene essential for the formation of photoreceptor cells. The expression of math5 coincides with the onset of retinal ganglion cell differentiation. The targeted deletion of mouse math5 revealed that a null mutation inhibits the formation of a majority of the retinal ganglion cells. The mutation also interferes with the normal development of other retinal cell types such as amacrine, bipolar and photoreceptor cells. These results suggest that math5 is a proneural gene responsible for differentiation of retinal ganglion cells and may also have a role in normal development of other neuronal cell types within the retina. ^ Myocilin has two unique protein coding regions bearing homology to non-muscle myosin of Dictyostelium discoideum and to olfactomedin, an extracellular matrix molecule first described in the olfactory epithelium of the bullfrog. Recently, autosomal dominant forms of myocilin mutations have been found in individuals with primary open-angle glaucoma. The genetic linkage to glaucoma suggests a role of myocilin in normal intraocular pressure and ocular function. However, the analysis of mice heterozygous and homozygous for a targeted null mutation in myocilin indicates that it is dispensable for normal intraocular pressure or ocular function. Additionally, the lack of a discernable phenotype in both heterozygous and null mice suggests that haploinsufficiency is not a critical mechanism for MYOC-associated glaucoma in humans. Instead, disease-causing mutations likely act by gain of function. ^ In summary, these studies provide novel insights into the embryonic development of the vertebrate retina, and also begin to uncover the molecular mechanisms responsible for the pathogenesis of glaucoma. ^

El humor luciánico en las Narrativas Verdaderas : una estética del desencanto

De la lectura de las Narrativas Verdaderas se sale sin conmoción y sin indiferencia, lo que no es una combinación sencilla de sensaciones y de algún modo nos obliga a corrernos de los roles habituales de la recepción para ‘pensar’. En la lectura que proponemos de Narrativas, Luciano se ubica dentro de la tradición filosófica cínica, basada en la acción y exigente de consecuencia entre el decir y el hacer. Desde su materialismo esencial se aparta, pues, del idealismo de su querido Platón y, a partir de ese sentido de la existencia y en consecuencia con él, encontramos una base para entender su sentido del humor. Para Luciano –y esto se hace evidente desde el título hasta la última escena de Narrativas–, la mentira y los mentirosos son cómicos en todas sus formas. Confrontar la mentira con la realidad de la vida es base de la risa luciánica; más allá de Aristóteles y su algo obvia definición de la risa como humana, Luciano especifica el concepto en dirección a lo ‘culturalmente humano’.

La construcción interactiva de la identidad en la entrevista periodística de humor : Categorías, ejecución y marcos

La identidad en la interacción ha sido objeto de numerosos estudios dentro de la Etnometodología. Esta investigación busca combinar los métodos de investigación del MCA (Membership Categorization Analysis) con la teoría de la ejecución y el concepto de alternancia de marcos para explicar el despliegue dinámico de la identidad de los participantes en entrevistas transcriptas. Utilizando los recursos retóricos, lingüísticos y discursivos que tienen a su disposición, los participantes construyen colaborativamente diferentes identidades para sí mismos y para el otro en el curso de la interacción, que están disponibles para la audiencia en la versión escrita. Los resultados muestran que el entrevistador construye su identidad posicionándose como performer o ejecutante (en el sentido de Bauman) frente a la audiencia (los futuros lectores de la entrevista) y a su entrevistado del momento, y alternando estratégicamente entre el marco humorístico y el marco serio. El entrevistador emplea una serie de recursos retóricos, discursivos y lingüísticos para producir el efecto cómico que ayudan a constituir su identidad como transgresor e ingenioso. Por otra parte, la identidad de los entrevistados se construye a través de procesos de auto y heterocategorización.

La construcción interactiva de la identidad en la entrevista periodística de humor : Categorías, ejecución y marcos

La identidad en la interacción ha sido objeto de numerosos estudios dentro de la Etnometodología. Esta investigación busca combinar los métodos de investigación del MCA (Membership Categorization Analysis) con la teoría de la ejecución y el concepto de alternancia de marcos para explicar el despliegue dinámico de la identidad de los participantes en entrevistas transcriptas. Utilizando los recursos retóricos, lingüísticos y discursivos que tienen a su disposición, los participantes construyen colaborativamente diferentes identidades para sí mismos y para el otro en el curso de la interacción, que están disponibles para la audiencia en la versión escrita. Los resultados muestran que el entrevistador construye su identidad posicionándose como performer o ejecutante (en el sentido de Bauman) frente a la audiencia (los futuros lectores de la entrevista) y a su entrevistado del momento, y alternando estratégicamente entre el marco humorístico y el marco serio. El entrevistador emplea una serie de recursos retóricos, discursivos y lingüísticos para producir el efecto cómico que ayudan a constituir su identidad como transgresor e ingenioso. Por otra parte, la identidad de los entrevistados se construye a través de procesos de auto y heterocategorización.

La construcción interactiva de la identidad en la entrevista periodística de humor : Categorías, ejecución y marcos

La identidad en la interacción ha sido objeto de numerosos estudios dentro de la Etnometodología. Esta investigación busca combinar los métodos de investigación del MCA (Membership Categorization Analysis) con la teoría de la ejecución y el concepto de alternancia de marcos para explicar el despliegue dinámico de la identidad de los participantes en entrevistas transcriptas. Utilizando los recursos retóricos, lingüísticos y discursivos que tienen a su disposición, los participantes construyen colaborativamente diferentes identidades para sí mismos y para el otro en el curso de la interacción, que están disponibles para la audiencia en la versión escrita. Los resultados muestran que el entrevistador construye su identidad posicionándose como performer o ejecutante (en el sentido de Bauman) frente a la audiencia (los futuros lectores de la entrevista) y a su entrevistado del momento, y alternando estratégicamente entre el marco humorístico y el marco serio. El entrevistador emplea una serie de recursos retóricos, discursivos y lingüísticos para producir el efecto cómico que ayudan a constituir su identidad como transgresor e ingenioso. Por otra parte, la identidad de los entrevistados se construye a través de procesos de auto y heterocategorización.

Ocean acidification not likely to affect the survival and fitness of two yemperate benthic foraminiferal species: results from culture experiments

Specimens of Bolivina argentea and Bulimina marginata, two widely distributed temperate benthic foraminiferal species, were cultured at constant temperature and controlled pCO2 (ambient, 1000 ppmv, and 2000 ppmv) for six weeks to assess the effect of elevated atmospheric CO2 concentrations on survival and fitness using Adenosine Triphosphate (ATP) analyses and on shell microfabric using high-resolution SEM and image analysis. To characterize the carbonate chemistry of the incubation seawater, total alkalinity and dissolved inorganic carbon were measured approximately every two weeks. Survival and fitness were not directly affected by elevated pCO2 and the concomitant decrease in seawater pH and calcite saturation states (Omega c), even when seawater was undersaturated with respect to calcite. These results differ from some previous observations that ocean acidification can cause a variety of effects on benthic foraminifera, including test dissolution, decreased growth, and mottling (loss of symbiont color in symbiont-bearing species), suggesting that the benthic foraminiferal response to ocean acidification may be species specific. If so, this implies that ocean acidification may lead to ecological winners and losers even within the same taxonomic group.