Assessing coastal vulnerability to climate change at regional scales is now mandatory in France since the adoption of recent laws to support adaptation to climate change. However, there is presently ...no commonly recognised method to assess accurately how sea level rise will modify coastal processes in the coming decades. Therefore, many assessments of the physical component of coastal vulnerability are presently based on a combined use of data (e.g. digital elevation models, historical shoreline and coastal geomorphology datasets), simple models and expert opinion. In this study, we assess the applicability and usefulness of a multi-criteria decision-mapping method (the analytical hierarchy process, AHP) to map physical coastal vulnerability to erosion and flooding in a structured way. We apply the method in two regions of France: the coastal zones of Languedoc-Roussillon (north-western Mediterranean, France) and the island of La Réunion (south-western Indian Ocean), notably using the regional geological maps. As expected, the results show not only the greater vulnerability of sand spits, estuaries and low-lying areas near to coastal lagoons in both regions, but also that of a thin strip of erodible cliffs exposed to waves in La Réunion. Despite gaps in knowledge and data, the method is found to provide a flexible and transportable framework to represent and aggregate existing knowledge and to support long-term coastal zone planning through the integration of such studies into existing adaptation schemes.
Environmental stressors that characterize intertidal habitats, such as exposure to air, thermal amplitude and wave action, influence biological patterns of distribution. The effects of these ...stressors on intertidal organisms are often associated with their shape and size. Rocky intertidal shores in Patagonia are particularly stressful environments in which a species of false limpet occurs abundantly in 2 contrasting habitats. Here we describe size and shape segregation of the false limpet Siphonaria lessonii across multiple shores on 2 contrasting shore levels where limpets are abundant, namely the high (HT) and mid (MT) intertidal. We tested for differences in resistance to desiccation, and recovery from heat stress, and were able to define 2 ecomorphs using classic and geometric morphometrics analysis. Individuals from the HT lost significantly less water under stressful heat conditions, and showed higher recovery rates than those from the MT. Limpets from the HT had a broad aperture, flatter margin and larger size. In contrast, individuals from the MT had a narrow aperture, arched margin and smaller size. Together these results suggest the existence of 2 ecomorphs modulated by each contrasting habitat. The observed small-scale spatial segregation of the 2 ecomorphs may provide ecological advantages by allowing the exploitation of resources from 2 different habitats. The 2 ecomorphs may provide S. lessonii with a broad thermal tolerance breadth, potentially improving resistance of the species to extreme climatic events.
Although normal aging has been related to several cognitive difficulties, other processes have been studied less, such as spatial memory. Our aim was to compare egocentric and allocentric memory in ...an elderly population using ecological tasks. Twenty-eight cognitively unimpaired participants performed Egocentric and Allocentric Spatial Memory Tasks, as well as Spatial Span from CANTAB, Benton's Judge of Line Orientation test (JoLO), and Montreal Cognitive Assessment test (MoCA). The results revealed that younger participants showed better performance than older participants on both the Egocentric and Allocentric Spatial Memory Tasks, although only the Egocentric test was able to discriminate between younger, middle, and older elderly participants. Learning effect was found in Allocentric Spatial Memory Task in younger and older groups, but not in the middle group. Allocentric and egocentric performance was not related to other visuospatial neuropsychological scores and gender did not influence performance in any task. Egocentric and Allocentric Spatial Memory Tasks may be useful tools in early screening for cognitive decline, as they are able to detect age differences in the cognitive unimpaired elderly population.
There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status ...measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.
We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).
In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS hazard ratio (HR), 3.98; 95% CI 1.74–9.10; P < 0.001 and HR 3.81; 95% CI 2.28–6.37; P < 0.001, respectively, PFS (HR 2.18; 95% CI 1.08–4.39; P = 0.03, and HR 1.95; 95% CI 1.23–3.11; P = 0.01, respectively) and rate of PSA decline≥50% odds ratio (OR), 4.7; 95% CI 1.17–19.17; P = 0.035 and OR, 5.0; 95% CI 1.70–14.91; P = 0.003, respectively. AR mutations 2105T>A (p.L702H) and 2632A>G (p.T878A) were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47–not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94–9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26–19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16–56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.
Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.
NCT02288936 (PREMIERE trial).
This study examined influences, factors, and processes associated with parental recognition and response to developmental concerns through interviews and focus groups with six Spanish- and 17 ...English-speaking parents of children aged 2 weeks to 4.5 years with developmental concerns. Results revealed that social support, perceptions of perceived threat (the child’s susceptibility to developmental problems and potential severity of the issue), evaluation of the benefits and barriers of seeking help, self-efficacy, and referral coordination influenced parents’ recognition and response to developmental concerns. Experiences and paths to services varied greatly, illustrating the lack of consistency within service systems. Understanding these influences in identification and intervention is the first step in addressing how to better support parents and their children.
Cortical spreading depression (CSD) is associated with migraine, stroke, and traumatic brain injury, but its mechanisms remain poorly understood. One of the major features of CSD is an hour-long ...silencing of neuronal activity. Though this silencing has clear ramifications for CSD-associated disease, it has not been fully explained. We used in vivo whole-cell recordings to examine the effects of CSD on layer 2/3 pyramidal neurons in mouse somatosensory cortex and used in vitro recordings to examine their mechanism. We found that CSD caused a reduction in spontaneous synaptic activity and action potential (AP) firing that lasted over an hour. Both pre- and postsynaptic mechanisms contributed to this silencing. Reductions in frequency of postsynaptic potentials were due to a reduction in presynaptic transmitter release probability as well as reduced AP activity. Decreases in postsynaptic potential amplitude were due to an inhibitory shift in the ratio of excitatory and inhibitory postsynaptic currents. This inhibitory shift in turn contributed to the reduced frequency of APs. Thus, distinct but complementary mechanisms generate the long neuronal silence that follows CSD. These cellular changes could contribute to wider network dysfunction in CSD-associated disease, while the pre- and postsynaptic mechanisms offer separate targets for therapy.
•We documented the highest infective rate by Leishmania in anthropophilic sand flies so far reported in Mexico.•Based on the biting rate and the infective biting rate of Phlebotomine sandflies, the ...potential increase in entomological and epidemiological exposure to L. (L.) mexicana continues to be associated primarily with conserved forests.•Our study also detected that, albeit to a lesser extent, human exposure to Leishmania is occurring in environments with intermediate and high disturbance.•Change in land use did not influence the pattern of nocturnal exposition to anthropophilic Phlebotomine sand fly.•Although temperature and humidity vary between sites with different land uses, these variables are not related to the biting rate or the infective biting rate of Phlebotomine sand flies.
Could tropical forest conversion shape sand fly (Diptera: Phlebotominae) biting rhythms and Leishmania infection rates? Using a Shannon trap, we estimated the bite rate and infection prevalence among anthropophilic sand flies at sites with different land use in southern Mexico. We estimated the expected monthly infection rate of the Leishmania parasite along the gradient and generated information on the biting rhythm of sand flies in a poorly characterized cutaneous leishmaniasis endemic region. We used generalized mixed linear and mixed additives models to evaluate differences in the biting rate, nocturnal activity, and inoculation rate of female sand flies, as well as their relationship with the loss of forest cover and environmental disparities recorded throughout the study area. Our results show that the loss of forest cover influences the biting rhythm of sand fly species and the potential number of infectious bites with Leishmania, but the greatest entomological and potential epidemiological risk continues to be associated with sylvatic areas (amplification events). Despite this, we detected that the effect of forest cover (%) on the entomological exposure seems to be also dependent on the sand fly species, and that, albeit to a lesser extent, Leishmania parasite is circulating in disturbed landscapes through generalist and competent sand fly vector species. We also found that land use change did not affect the nocturnal activity, however we detected that important vector species were active most of the time. Contrary to our expectation, temperature and humidity did not shape the biting rhythm of sand fly species. We discuss the limitations and epidemiological implications of our findings regarding the risk of contracting leishmaniasis in southern Mexico.
Respiratory infections are a leading cause of morbidity and mortality in early life, and recurrent infections increase the risk of developing chronic diseases. The maternal environment during ...pregnancy can impact offspring health, but the factors leading to increased infection proneness have not been well characterized during this period. Steroids have been implicated in respiratory health outcomes and may similarly influence infection susceptibility. Our objective was to describe relationships between maternal steroid levels and offspring infection proneness. Using adjusted Poisson regression models, we evaluated associations between sixteen androgenic and corticosteroid metabolites during pregnancy and offspring respiratory infection incidence across two pre-birth cohorts (N = 774 in VDAART and N = 729 in COPSAC). Steroid metabolites were measured in plasma samples from pregnant mothers across all trimesters of pregnancy by ultrahigh-performance-liquid-chromatography/mass-spectrometry. We conducted further inquiry into associations of steroids with related respiratory outcomes: asthma and lung function spirometry. Higher plasma corticosteroid levels in the third trimester of pregnancy were associated with lower incidence of offspring respiratory infections (P = 4.45 × 10
to 0.002) and improved lung function metrics (P = 0.020-0.036). Elevated maternal androgens were generally associated with increased offspring respiratory infections and worse lung function, with some associations demonstrating nominal significance at P < 0.05, but these trends were inconsistent across individual androgens. Increased maternal plasma corticosteroid levels in the late second and third trimesters were associated with lower infections and better lung function in offspring, which may represent a potential avenue for intervention through corticosteroid supplementation in late pregnancy to reduce offspring respiratory infection susceptibility in early life.Clinical Trial Registry information: VDAART and COPSAC were originally conducted as clinical trials; VDAART: ClinicalTrials.gov identifier NCT00920621; COPSAC: ClinicalTrials.gov identifier NCT00798226.
An analysis of the symmetries characterizing the micro-architecture topologies and the elastic material properties is performed. The goal is to elucidate a systematic procedure that facilitates the ...design of elastic metamaterial with a prescribed target elasticity tensor via inverse homogenization methodologies. This systematic procedure, which is defined through a set of rules, is based on the relationship established between the elasticity tensor symmetries and the symmetry displayed by the micro-architecture topology.
Following this procedure, it can be guaranteed that the designed composites, with the attained micro-structures, have effective elasticity tensors that possess the same or higher symmetries than those shown by the target elasticity tensors. Furthermore, the micro-architectures designed through this technique display simple topologies.
Both properties that are supplied by the procedure, i.e., the accomplishment of the required symmetry of the composite homogenized elasticity tensor combined with the topology simplicity, are assessed through numerical simulations of several micro-architecture design problems. They are designed by formulating the inverse homogenization problem as a topology optimization problem which is solved with two different standard algorithms. The proposed procedure and the conclusions here obtained do not depend on the algorithm adopted for solving this problem.
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