Indirect Impact Assessment of Pluvial Flooding in Urban Areas Using a Graph-Based Approach: The Mexico City Case Study

This paper presents the application of a graph-based methodology for the assessment of flood impacts in an urban context. In this methodology, exposed elements are organized as nodes on a graph, which is used to propagate impacts from directly affected nodes to other nodes across graph links. Compared to traditional approaches, the main advantage of the adopted methodology lies in the possibility of identifying and understanding indirect impacts and cascading effects. The application case concerns floods numerically reconstructed in Mexico City in response to rainfall events of increasing return periods. The hazard reconstruction was carried out by using a simplified hydrological/hydraulic model of the urban drainage system, implemented in EPASWMM, the Storm Water Management Model developed by the United States Environmental Protection Agency. The paper shows how the impacts are propagated along different orders of the impact chain for each return period and compares the risk curves between direct and indirect impact. It also highlights the extent to which the reduction in demand of services from consumers and the loss of services from suppliers are respectively contributing to the final indirect impacts. Finally, it illustrates how different impact mitigation measures can be formulated based on systemic information provided by the analysis of graph properties and taking into account indirect impacts

Anti-inflammatory effects of fatty acid amide hydrolase inhibition in monocytes/macrophages from alzheimer’s disease patients

Growing evidence shows that the immune system is critically involved in Alzheimer’s disease (AD) pathogenesis and progression. The modulation and targeting of peripheral immune mechanisms are thus promising therapeutic or preventive strategies for AD. Given the critical involvement of the endocannabinoid (eCB) system in modulating immune functions, we investigated the potential role of the main elements of such a system, namely type-1 and type-2 cannabinoid receptors (CB1 and CB2), and fatty acid amide hydrolase (FAAH), in distinct immune cell populations of the peripheral blood of AD patients. We found that, compared to healthy controls, CB1 and CB2 expression was significantly lower in the B-lymphocytes of AD patients. Moreover, we found that CB2 was significantly lower and FAAH was significantly higher in monocytes of the same subjects. In contrast, T-lymphocytes and NK cells did not show any variation in any of these proteins. Of note, monocytic CB2 and FAAH levels significantly correlated with clinical scores. Furthermore, the pharmacological inactivation of FAAH in monocytes and monocyte-derived macrophages obtained from AD patients was able to modulate their immune responses, by reducing production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-12, and enhancing that of the anti-inflammatory cytokine IL-10. Furthermore, FAAH blockade skewed AD monocyte-derived macrophages towards a more anti-inflammatory and pro-resolving phenotype. Collectively, our findings highlight a central role of FAAH in regulating AD monocytes/macrophages that could be of value in developing novel monocyte-centered therapeutic approaches aimed at promoting a neuroprotective environment

Functional and Environmental Performances of Novel Electrolytic Membranes for PEM Fuel Cells: A Lab-Scale Case Study

Despite being the most employed polymer electrolyte for proton exchange membrane fuel cells (PEMFCs), Nafion® has several limitations: expensiveness, poor performance when exposed to temperatures higher than 80 °C, and its potential as a source of environmentally persistent and toxic compounds (i.e., per- and polyfluoroalkyl substances, known as PFASs) when disposed of. This work explores the functional and environmental performances of three potential PFAS-free alternatives to Nafion® as electrolytic membranes in PEMFCs: sulfonated graphene oxide (SGO), graphene oxide-naphthalene sulfonate (GONS), and borate-reinforced sulfonated graphene oxide (BSGO). Investigated via ATR-FTIR spectroscopy, TGA, and cross-sectional SEM, the membranes show an effective functionalization of GO and good thermal stability. Functional properties are determined via Ion Exchange Capacity (IEC) evaluation, Electrochemical Impedance Spectroscopy, and tensile tests. In terms of IEC, the innovative materials outperform Nafion® 212. Proton conductivities at 80 °C of SGO (1.15 S cm-1) and GONS (1.71 S cm-1) are higher than that of the commercial electrolyte (0.56 S cm-1). At the same time, the membranes are investigated via Life Cycle Assessment (LCA) to uncover potential environmental hotspots. Results show that energy consumption during manufacture is the main environmental concern for the three membranes. A sensitivity analysis demonstrates that the impact could be significantly reduced if the production procedures were scaled up. Among the three alternatives, SGO shows the best trade-off between proton conductivity and environmental impact, even though performance results from real-life applications are needed to determine the actual environmental consequences of replacing Nafion® in PEMFCs

ENVIRONMENTAL IMPACTS OF USING DESALINATED WATER IN CONCRETE PRODUCTION IN AREAS AFFECTED BY FRESHWATER SCARCITY

Up to 500 litres of water may be consumed at the batching plant per cubic meter of ready mix concrete, if water for washing mixing trucks and equipment is included. Demand for concrete is growing almost everywhere, regardless of local availability of freshwater. The use of freshwater for concrete production exacerbates stress on natural water resources. In water-stressed coastal countries such as Israel, desalinated seawater (DSW) is often used in the production of concrete. However, the environmental impacts of this practice have not yet been assessed. In this study the effect of using DSW on the water and carbon footprints of concrete was investigated using life cycle assessment. Water footprint results highlight the benefits of using DSW rather than freshwater to produce concrete in Israel. In contrast, because desalination is an energy intensive process, using DSW increases the greenhouse gas intensity of concrete. Nevertheless, this increase (0.27 kg CO2e/m3 concrete) is small, if compared to the life cycle greenhouse gas emissions of concrete. Our results show that using untreated seawater in the mix (transported by truck from the coast) in place of DSW, would be beneficial in terms of water and carbon footprints if the batching plant were located less than 13 km from the withdrawal point. However, use of untreated seawater increases steel reinforcement corrosion, resulting in loss of structural integrity of the reinforced concrete composite. Sustainability of replacing steel with non-corrosive materials should be explored as a way to reduce both water and carbon footprints of concrete

Geoelectrical characterization and monitoring of slopes on a rainfall-triggered landslide simulator

In this paper, we present the results of time-lapse electrical resistivity tomography (ERT) monitoring of rainfall-triggered shallow landslides reproduced on a laboratory-scale physical model. The main objective of our experiments was to monitor rainwater infiltration through landslide body in order to improve our understanding of the precursors of failure. Time-domain reflectometry (TDR) data were also acquired to obtain the volumetric water content. Knowing the porosity, water saturation was calculated from the volumetric water content and we could calibrate Archie's equation to calculate water saturation maps from inverted resistivity values. Time-lapse ERT images proved to be effective in monitoring the hydrogeological conditions of the slope as well as in detecting the development of fracture zones before collapse. We performed eight laboratory tests and the results show that the landslide body becomes unstable at zones where the water saturation exceeds 45%. It was also observed that instability could occur at the boundaries between areas with different water saturations. Our study shows that time-lapse ERT technique can be employed to monitor the hydrogeological conditions of landslide bodies and the monitoring strategy could be extended to field-scale applications in areas prone to the development of shallow landslides

Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience

Purpose: The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test. Methods: We enrolled 30 patients (age 47 \ub1 21 years) referred to undergo the ACTH test (1 or 250 \u3bcg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L. Results: Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 \ub1 177, 287 \ub1 119, and 295 \ub1 119 nmol/L; at 30 min, 704 \ub1 204, 480 \ub1 132, and 500 \ub1 132 nmol/L; at 60 min, 737 \ub1 301, 502 \ub1 196, and 519 \ub1 201 nmol/L, p 64 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 \u3bcg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 \u3bcg/dL) with LC-MS/MS. Conclusions: The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted

Synthesis and Biological Evaluation (in Vitro and in Vivo) of Cyclic RGD Peptidomimetic - Paclitaxel Conjugates Targeting Integrin alphaVbeta3

A small library of integrin ligand - Paclitaxel conjugates 10-13 was synthesized with the aim of using the tumor-homing cyclo[DKP-RGD] peptidomimetics for site-directed delivery of the cytotoxic drug. All the Paclitaxel-RGD constructs 10-13 inhibited biotinylated vitronectin binding to the purified alphaVbeta3 integrin receptor at low nanomolar concentration and showed in vitro cytotoxic activity against a panel of human tumor cell lines similar to that of Paclitaxel. Among the cell lines, the cisplatin-resistant IGROV-1/Pt1 cells expressed high levels of integrin alphaVbeta3, making them attractive to be tested in in vivo models. Cyclo[DKP-f3-RGD]-PTX 11 displayed sufficient stability in physiological solution and in both human and murine plasma to be a good candidate for in vivo testing. In tumor-targeting experiments against the IGROV-1/Pt1 human ovarian carcinoma xenotransplanted in nude mice, compound 11 exhibited a superior activity than Paclitaxel, despite the lower (ca. half) molar dosage used

Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels

Ghrelin, the recently identified endogenous ligand of the GH secretagogue receptor, is a gut-brain peptide with endocrine, orexigenic, and gastrointestinal effects. In rodents it increases circulating gastrin and insulin levels, whereas in man it appears to decrease insulin secretion despite a rise in blood glucose levels. The aim of the present study was to evaluate the effects of ghrelin administration on total circulating somatostatin (SS), pancreatic polypeptide (PP), and gastrin levels compared with those elicited on insulin, glucose, and GH. Eight healthy volunteers of normal weight (four women and four men) were injected with 3.3 \u3bcg/kg ghrelin or saline after an overnight fast on 2 different days. Blood was taken every 15 min for 1 h and then every 30 min for 2 h. As expected, ghrelin injection elicited a prompt GH and glucose increase with a peak at 30 min and an insulin decrease with a nadir at 60 min. Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min). A significant negative correlation was found between SS (first peak) and insulin changes (r = -0.86; P < 0.01). In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man. Although the underlying mechanisms and biological significance of these pharmacological effects remain to be elucidated, a causal relationship between the SS increase and the insulin changes may be hypothesized. Finally, these findings strongly support ghrelin's postulated role in linking the endocrine control of energy balance and growth with the regulation of gastrointestinal functions

Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly

OBJECTIVE: Radiotherapy (RT) has been used for many years in order to complete the cure of unsuccessfully operated acromegalic patients. Several studies have shown its efficacy in normalizing GH levels, while reports about IGF-I normalization are conflicting. Moreover, data regarding other markers of disease activity, such as IGFBP-3 and acid-labile subunit (ALS), i.e. the other two components of the circulating 150 kDa complex, are lacking. DESIGN: Retrospective study. PATIENTS AND MEASUREMENTS: Sixty-seven acromegalic patients (20 males and 47 females, aged 40 \ub1 6 years) who underwent postoperative RT (in fractionated doses for a total of 40-75 Gy) were followed-up for 11 \ub1 6 years (range: 1-26 years, median: 10 years). Serum GH and IGF-I levels off medical therapy were measured in all patients; ALS and IGFBP-3 were measured in 11 patients with normalization of IGF-I concentrations. Computed tomography or nuclear magnetic resonance imaging periodically assessed possible development of pituitary deficiency along with imaging of the hypothalamic-pituitary region. RESULTS: Forty-one out of 67 patients (58%) achieved GH levels < 2.5 \u3bcg/l by 1-15 years after RT (mean 8 \ub1 6) and 37/67 patients (55%) had normal or low IGF-I levels 1-26 years after RT (mean: 12 \ub1 6), a normalization of both parameters being seen in 37 patients. GH < 2.5 \u3bcg/l and normal IGF-I levels were achieved in 17/26 (65%) patients followed-up for at least 15 years. ALS and IGFBP-3 concentrations paralleled IGF-I levels in all patients studied. With respect to secondary pituitary insufficiency, acquired ACTH deficiency was found in 25 patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency in seven. In total, two cases of meningioma and one pineal tumour, possibly related to RT, were seen 9-22 years after RT. CONCLUSIONS: RT is an effective, although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and normal IGF-I concentrations being achieved in 65% of patients after 15 years. IGF-I levels normalize more slowly than GH levels. Radiotherapy is able to normalize the concentration of all three components of the circulating 150 kDa complex. Checks for loss of pituitary function and appearance of second brain tumours must be carried out life-long