Bridge-specific fragility analysis: when is it really necessary?

In seismic assessment of bridges the research focus has recently shifted on the derivation of bridge-specific fragility curves that account for the effect of different geometry, structural system, component and soil properties, on the seismic behaviour. In this context, a new, component-based methodology for the derivation of bridge-specific fragility curves has been recently proposed by the authors, with a view to overcoming the inherent difficulties in assessing all bridges of a road network and the drawbacks of existing methodologies, which use the same group of fragility curves for bridges within the same typological class. The main objective of this paper is to critically assess the necessity of bridge-specific fragility analysis, starting from the effect of structure-specific parameters on component capacity (limit state thresholds), seismic demand, and fragility curves. The aforementioned methodology is used to derive fragility curves for all bridges within an actual road network, with a view to investigating the consistency of adopting generic fragility curves for bridges that fall within the same class and quantifying the degree of over- or under-estimation of the probability of damage when generic bridge classes are considered. Moreover, fragility curves for all representative bridges of the analysed concrete bridge classes are presented to illustrate the differentiation in bridge fragility for varying structural systems, bridge geometry, total bridge length and maximum pier height. Based on the above, the relevance of bridge-specific fragility analysis is assessed, and pertinent conclusions are drawn

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

In vitro metabolism of beclomethasone dipropionate, budesonide, ciclesonide, and fluticasone propionate in human lung precision-cut tissue slices

<p>Abstract</p> <p>Background</p> <p>The therapeutic effect of inhaled corticosteroids (ICS) may be affected by the metabolism of the drug in the target organ. We investigated the <it>in vitro </it>metabolism of beclomethasone dipropionate (BDP), budesonide (BUD), ciclesonide (CIC), and fluticasone propionate (FP) in human lung precision-cut tissue slices. CIC, a new generation ICS, is hydrolyzed by esterases in the upper and lower airways to its pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC).</p> <p>Methods</p> <p>Lung tissue slices were incubated with BDP, BUD, CIC, and FP (initial target concentration of 25 μM) for 2, 6, and 24 h. Cellular viability was assessed using adenosine 5'-triphosphate content and protein synthesis in lung slices. Metabolites and remaining parent compounds in the tissue samples were analyzed by HPLC with UV detection.</p> <p>Results</p> <p>BDP was hydrolyzed to the pharmacologically active metabolite beclomethasone-17-monopropionate (BMP) and, predominantly, to inactive beclomethasone (BOH). CIC was hydrolyzed initially to des-CIC with a slower rate compared to BDP. A distinctly smaller amount (approximately 10-fold less) of fatty acid esters were formed by BMP (and/or BOH) than by BUD or des-CIC. The highest relative amounts of fatty acid esters were detected for BUD. For FP, no metabolites were detected at any time point. The amount of drug-related material in lung tissue (based on initial concentrations) at 24 h was highest for CIC, followed by BUD and FP; the smallest amount was detected for BDP.</p> <p>Conclusion</p> <p>The <it>in vitro </it>metabolic pathways of the tested ICS in human lung tissue were differing. While FP was metabolically stable, the majority of BDP was converted to inactive polar metabolites. The formation of fatty acid conjugates was confirmed for BMP (and/or BOH), BUD, and des-CIC.</p

Association of HIV status with sexual function in women aged 45-60 in England: results from two national surveys

Increasing numbers of women living with HIV are reaching their midlife. We explore the association of HIV status with sexual function (SF) in women aged 45-60 using two national cross-sectional surveys: the third British National Survey of Sexual Attitudes and Lifestyles ("Natsal-3") and "PRIME", a survey of women living with HIV attending HIV clinics across England. Both studies asked the same questions about SF that take account not only sexual difficulties but also the relationship context and overall level of satisfaction, which collectively allowed an overall SF score to be derived. We undertook analyses of sexually-active women aged 45-60 from Natsal-3 (N = 1228, presumed HIV-negative given the low estimated prevalence of HIV in Britain) and PRIME (N = 386 women living with HIV). Women living with HIV were compared to Natsal-3 participants using multivariable logistic regression (adjusting for key confounders identified a priori: ethnicity, ongoing relationship status, depression and number of chronic conditions) and propensity scoring. Relative to Natsal-3 participants, women living with HIV were more likely to: have low overall SF (adjusted odds ratio (AOR) 3.75 [2.15-6.56]), report ≥1 sexual problem(s) lasting ≥3 months (AOR 2.44 [1.49-4.00]), and report almost all 8 sexual problems asked about (AORs all ≥2.30). The association between HIV status and low SF remained statistically significant when using propensity scoring (AOR 2.43 [1.68-3.51]). Among women living with HIV (only), low SF was more common in those who were postmenopausal vs. Premenopausal (55.6% vs. 40.4%). This study suggests a negative association between HIV status and sexual function in women aged 45-60. We recommend routine assessment of SF in women living with HIV

Tumor immunosurveillance in human cancers

Until now, the anatomic extent of tumor (TNM classification) has been by far the most important factor to predict the prognosis of colorectal cancer patients. However, in recent years, data collected from large cohorts of human cancers demonstrated that the immune contexture of the primary tumors is an essential prognostic factor for patients’ disease-free and overall survival. Tumoral and immunological markers predicted by systems biology methods are involved in the shaping of an efficient immune reaction and can serve as targets for novel therapeutic approaches. Global analysis of tumor microenvironment showed that the nature, the functional orientation, the density, and the location of adaptive immune cells within distinct tumor regions influence the risk of relapse events. The density and the immune cell location within the tumor have a prognostic value that is superior to the TNM classification, and tumor invasion is statistically dependent on the host-immune reaction. Thus, the strength of the immune reaction could advance our understanding of cancer evolution and have important consequences in clinical practice

The Effects of Copper Pollution on Fouling Assemblage Diversity: A Tropical-Temperate Comparison

BACKGROUND: The invasion of habitats by non-indigenous species (NIS) occurs at a global scale and can generate significant ecological, evolutionary, economic and social consequences. Estuarine and coastal ecosystems are particularly vulnerable to pollution from numerous sources due to years of human-induced degradation and shipping. Pollution is considered as a class of disturbance with anthropogenic roots and recent studies have concluded that high frequencies of disturbance may facilitate invasions by increasing the availability of resources. METHODOLOGY/PRINCIPAL FINDINGS: To examine the effects of heavy metal pollution as disturbance in shaping patterns of exotic versus native diversity in marine fouling communities we exposed fouling communities to different concentrations of copper in one temperate (Virginia) and one tropical (Panama) region. Diversity was categorized as total, native and non-indigenous and we also incorporated taxonomic and functional richness. Our findings indicate that total fouling diversity decreased with increasing copper pollution, whether taxonomic or functional diversity is considered. Both native and non-indigenous richness decreased with increasing copper concentrations at the tropical site whereas at the temperate site, non-indigenous richness was too low to detect any effect. CONCLUSIONS/SIGNIFICANCE: Non-indigenous richness decreased with increasing metal concentrations, contradicting previous investigations that evaluate the influence of heavy metal pollution on diversity and invasibility of fouling assemblages. These results provide first insights on how the invasive species pool in a certain region may play a key role in the disturbance vs. non-indigenous diversity relationship

A Complete Pathway Model for Lipid A Biosynthesis in Escherichia coli.

Lipid A is a highly conserved component of lipopolysaccharide (LPS), itself a major component of the outer membrane of Gram-negative bacteria. Lipid A is essential to cells and elicits a strong immune response from humans and other animals. We developed a quantitative model of the nine enzyme-catalyzed steps of Escherichia coli lipid A biosynthesis, drawing parameters from the experimental literature. This model accounts for biosynthesis regulation, which occurs through regulated degradation of the LpxC and WaaA (also called KdtA) enzymes. The LpxC degradation signal appears to arise from the lipid A disaccharide concentration, which we deduced from prior results, model results, and new LpxK overexpression results. The model agrees reasonably well with many experimental findings, including the lipid A production rate, the behaviors of mutants with defective LpxA enzymes, correlations between LpxC half-lives and cell generation times, and the effects of LpxK overexpression on LpxC concentrations. Its predictions also differ from some experimental results, which suggest modifications to the current understanding of the lipid A pathway, such as the possibility that LpxD can replace LpxA and that there may be metabolic channeling between LpxH and LpxB. The model shows that WaaA regulation may serve to regulate the lipid A production rate when the 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) concentration is low and/or to control the number of KDO residues that get attached to lipid A. Computation of flux control coefficients showed that LpxC is the rate-limiting enzyme if pathway regulation is ignored, but that LpxK is the rate-limiting enzyme if pathway regulation is present, as it is in real cells. Control also shifts to other enzymes if the pathway substrate concentrations are not in excess. Based on these results, we suggest that LpxK may be a much better drug target than LpxC, which has been pursued most often

First record of Rhabdoceras suessi (Ammonoidea, Late Triassic) from the Transylvanian Triassic Series of the Eastern Carpathians (Romania) and a review of its biochronology, paleobiogeography and paleoecology

Abstract The occurrence of the heteromorphic ammonoid Rhabdoceras suessi Hauer, 1860, is recorded for the first time in the Upper Triassic limestone of the Timon-Ciungi olistolith in the Rarău Syncline, Eastern Carpathians. A single specimen of Rhabdoceras suessi co-occurs with Monotis (Monotis) salinaria that constrains its occurrence here to the Upper Norian (Sevatian 1). It is the only known heteromorphic ammonoid in the Upper Triassic of the Romanian Carpathians. Rhabdoceras suessi is a cosmopolitan species widely recorded in low and mid-paleolatitude faunas. It ranges from the Late Norian to the Rhaetian and is suitable for high-resolution worldwide correlations only when it co-occurs with shorter-ranging choristoceratids, monotid bivalves, or the hydrozoan Heterastridium. Formerly considered as the index fossil for the Upper Norian (Sevatian) Suessi Zone, by the latest 1970s this species lost its key biochronologic status among Late Triassic ammonoids, and it generated a controversy in the 1980s concerning the status of the Rhaetian stage. New stratigraphic data from North America and Europe in the subsequent decades resulted in a revised ammonoid biostratigraphy for the uppermost Triassic, the Rhaetian being reinstalled as the topmost stage in the current standard timescale of the Triassic. The geographic distribution of Rhabdoceras is compiled from published worldwide records, and its paleobiogeography and paleoecology are discussed

A New Direction to Athletic Performance: Understanding the Acute and Longitudinal Responses to Backward Running

Backward running (BR) is a form of locomotion that occurs in short bursts during many overground field and court sports. It has also traditionally been used in clinical settings as a method to rehabilitate lower body injuries. Comparisons between BR and forward running (FR) have led to the discovery that both may be generated by the same neural circuitry. Comparisons of the acute responses to FR reveal that BR is characterised by a smaller ratio of braking to propulsive forces, increased step frequency, decreased step length, increased muscle activity and reliance on isometric and concentric muscle actions. These biomechanical differences have been critical in informing recent scientific explorations which have discovered that BR can be used as a method for reducing injury and improving a variety of physical attributes deemed advantageous to sports performance. This includes improved lower body strength and power, decreased injury prevalence and improvements in change of direction performance following BR training. The current findings from research help improve our understanding of BR biomechanics and provide evidence which supports BR as a useful method to improve athlete performance. However, further acute and longitudinal research is needed to better understand the utility of BR in athletic performance programs

Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes

We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.H2020 Marie Skłodowska-Curie Action