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Space and time play a crucial role in multi-hazard damage assessment. When two or more natural hazards occur simultaneously in the same location or within a short time frame, the physical integrity of infrastructure can be compromised, leading to two scenarios: (i) 'spatial-temporal overlapping impact', when the damage results from the combined impact of both hazards, and (ii)' overlapping spatial impact with residual and subsequent damage', in case of cumulative damage from consecutive hazards. Current literature highlights the lack of clear frameworks for multi-hazard impact assessment. Complexity in formalising quantitative aspects and understanding feedback loops between hazard, exposure and vulnerability emphasises this gap. This research aims to develop a generalised mathematical framework for quantitatively assessing multi-hazard physical damage on exposed assets, such as buildings or critical infrastructures, over time. The proposed framework covers both cases of compound and consecutive hazards. Specifically, in the "overlapping spatial impacts with residual and subsequent damage" scenario, the framework considers the reduction in exposure value, modification of vulnerability, and recovery dynamics. A sensitivity analysis has been conducted to evaluate how the duration of recovery and its functional shape (linear, exponential, and logarithmic) affect the asset's resilience.The framework is tested through a series of real and virtual case studies, demonstrating its applicability. Observing real scenarios allows the assessment of socioeconomic and institutional factors influencing the single and multi-hazard recovery process. By incorporating dynamic analysis into the recovery phase, we can offer decision-makers a comprehensive understanding of the impacts caused by compound and consecutive events., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

To keep up with increasing demand for animal protein, alternative protein sources will need to be included in current animal production systems. The efficient growth of Hermetia illucens larvae combined with municipal waste as a substrate has the potential to increase the sustainability of protein feed production. Therefore, this study partially substituted soymeal with H. illucens larval meal (reared on municipal waste) in broiler diets to determine the effect on slow-growing broiler (ISA-JA-757 and Les Bleues) production. Growth and slaughter performance, as well as animal welfare and meat quality parameters were evaluated. No influence of H. illucens larvae meal in the diet was found for weight gain, feed efficiency and slaughter performance. Animal welfare was also not influenced by diet. Fatty acid composition of intramuscular fat was influenced by the inclusion of H. illucens in the broiler diets; however not uniformly across meat cut. Differences between animal genotype and animal sex often influenced parameters under investigation more than diet itself. Overall, H. illucens can be regarded as a suitable protein source in slow-growing broiler diets.

Highlight Ethylene affects adventitious rooting by reducing indole-3-acetic acid (IAA) biosynthesis, but enhancing conversion into IAA of its precursor indole-3-butyric acid (IBA). This conversion, together with active IAA-cellular-influx, is essential for adventitious root formation., Adventitious roots (ARs) are post-embryonic roots essential for plant survival and propagation. Indole-3-acetic acid (IAA) is the auxin that controls AR formation; however, its precursor indole-3-butyric acid (IBA) is known to enhance it. Ethylene affects many auxin-dependent processes by affecting IAA synthesis, transport and/or signaling, but its role in AR formation has not been elucidated. This research investigated the role of ethylene in AR formation in dark-grown Arabidopsis thaliana seedlings, and its interaction with IAA/IBA. A number of mutants/transgenic lines were exposed to various treatments, and mRNA in situ hybridizations were carried out and hormones were quantified In the wild-type, the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) at 0.1 μM enhanced AR formation when combined with IBA (10 μM), but reduced it when applied alone; this effect did not occur in the ein3eil1 ethylene-insensitive mutant. ACC inhibited the expression of the IAA-biosynthetic genes WEI2, WEI7, and YUC6, but enhanced IBA-to-IAA conversion, as shown by the response of the ech2ibr10 mutant and an increase in the endogenous levels of IAA. The ethylene effect was independent of auxin-signaling by TIR1-AFB2 and IBA-efflux by ABCG carriers, but it was dependent on IAA-influx by AUX1/LAX3. Taken together, the results demonstrate that a crosstalk involving ethylene signaling, IAA-influx, and IBA-to-IAA conversion exists between ethylene and IAA in the control of AR formation.

Oxygen supply plays a central role in cancer cell proliferation. While vascular density increases at the early stages of carcinogenesis, mechanical solid stresses developed during growth compress tumor blood vessels and, thus, drastically reduce not only the supply of oxygen, but also the delivery of drugs at inner tumor regions. Among other effects, hypoxia and reduced drug delivery compromise the efficacy of radiation and chemo/nanotherapy, respectively. In the present study, we developed a mathematical model of tumor growth to investigate the interconnections among tumor oxygenation that supports cancer cell proliferation, the heterogeneous accumulation of mechanical stresses owing to tumor growth, the non-uniform compression of intratumoral blood vessels due to the mechanical stresses, and the insufficient delivery of oxygen and therapeutic agents because of vessel compression. We found that the high vascular density and increased cancer cell proliferation often observed in the periphery compared to the interior of a tumor can be attributed to heterogeneous solid stress accumulation. Highly vascularized peripheral regions are also associated with greater oxygenation compared with the compressed, less vascularized inner regions. We also modeled the delivery of drugs of two distinct sizes, namely chemotherapy and nanomedicine. Model predictions suggest that drug delivery is affected negatively by vessel compression independently of the size of the therapeutic agent. Finally, we demonstrated the applicability of our model to actual geometries, employing a breast tumor model derived from MR images. © 2015, Springer-Verlag Berlin Heidelberg. 14 1391 1402 1391-1402

The mouth-throat plays a key role in the administration of inhaled medicines. It is an area of intense filtration, where an unacceptably high fraction of the released drug dose is deposited and thus wasted. Due to the relatively high flow rate associated with Dry Powder Inhalers (DPIs), drug particles are released at a high velocity, which causes substantial deposition in the oral cavity and the throat region by inertial impaction. Hence, reducing the mouththroat deposition is of utmost importance and this can only be achieved by designing more efficient inhaler devices (functioning at lower flow rates) and by obtaining a better understanding of the mechanisms that cause the oropharyngeal losses. The present study is designed to identify the main factors that determine aerosol deposition (unwanted filtering) in the mouththroat region, with the aim of controlling the leading effects that contribute to the oropharyngeal deposition losses for drugs delivered via DPIs. For this reason micron-sized particles are released and tracked in a patient-specific MRI-based mouth-throat geometry under three inhalation flow rates (15L/min, 30L/min, 60L/min), three head positions (straight, up, left), and three inhaler mouthpiece orientations (0o, 15o, 30o). Direct Numerical Simulations (DNS) are performed for the low flow rate using prescribed laminar inlet conditions, while Large Eddy Simulations (LES) are performed for the intermediate and high flow rates using fullydeveloped turbulent inlet conditions. Interestingly, our results reveal that the deposition fraction is insensitive to the head position, whilst the inhalation flow rate and the inhaler mouthpiece orientation have a strong influence on the aerosol deposition in the mouth-throat region. Furthermore, we illustrate the mean flow structures and examine their effect on the particle deposition of various micron sizes. Despite the fact that our results are case specific, we expect the main trends to be universal. 1

Traumatic brain injury results in brain tissue swelling which can be a life threatening condition due to skull confinement. While previous efforts successfully measured the exhibited volume change in brain tissue swelling, no data exist to provide information about the exhibited stresses. In this study, confined compression mechanical testing was employed to measure swelling stress in murine brain tissue samples by varying the ionic concentration of the bathing solutions. Subsequently, computer simulations of the experimental protocol were employed to confirm a triphasic mathematical model describing the effect and provide insights into the experimental data. We measured the swelling stress to be in the range of 1.2–6.7 kPa (9.0–50.2 mmHg) depending on the ionic strength of the bathing solution, while a good correspondence was demonstrated among the experimentally measured and simulated responses. Furthermore, the mathematical model featured the osmotic pressure as the primary contributor to the swelling stress, while a parametric analysis showed that the densities of the intracellular fixed charges and of the non-permeable solutes significantly affect the swelling stress. © 2017 Elsevier Ltd 56 42 47 42-47

To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.

Brainstem and cerebellar plaques often result in some of the most disabling symptoms experienced by persons with multiple sclerosis, and may be among the most challenging to treat. The impairments resulting from these lesions may also be a significant source of secondary complications such as falls, aspiration, and poor nutrition. This chapter outlines the anatomical origin of dysfunction, clinical findings, and treatment options available to patients and providers. Medical, surgical, and rehabilitative methods for the treatment of tremors, ataxia, vertigo, dysphagia, dysarthria, dysphonia, trigeminal neuralgia, and facial nerve palsy are reviewed.

Oxygen supply plays a central role in cancer cell proliferation. While vascular density increases at the early stages of carcinogenesis, mechanical solid stresses developed during growth compress tumor blood vessels and, thus, drastically reduce the supply of oxygen, but also the delivery of drugs at inner tumor regions. Among other effects, hypoxia and reduced drug delivery compromise the efficacy of radiation and chemo/nano therapy, respectively. In the present study, we developed a mathematical model of tumor growth to investigate the interconnections among tumor oxygenation that supports cancer cell proliferation, the heterogeneous accumulation of mechanical stresses owing to tumor growth, the nonuniform compression of intratumoral blood vessels due to the mechanical stresses, and the insufficient delivery of oxygen and therapeutic agents because of vessel compression. We found that the high vascular density and increased cancer cell proliferation often observed in the periphery compared to the interior of a tumor can be attributed to heterogeneous solid stress accumulation. Highly vascularized peripheral regions are also associated with greater oxygenation compared with the compressed, less vascularized inner regions. We also modeled the delivery of drugs of two distinct sizes, namely chemotherapy and nanomedicine. Model predictions suggest that drug delivery is negatively affected by vessel compression independently of the size of the therapeutic agent. Finally, we demonstrated the applicability of our model to actual geometries, employing a breast tumor model derived from MR images. © Springer International Publishing Switzerland 2016. 57 614 617 614-617

Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35% spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning. © 2016 Elsevier Ltd. 49 1524 1531 1524-1531

Bees can be severely affected by various plant protection products (PPP). Among these, neonicotinoid insecticides are of concern as they have been shown to be responsible for extensive honeybee colonies death when released into the environment. Also, sublethal neonicotinoid doses contaminating single honeybees and their colonies (e.g. through contaminated pollen) are responsible for honeybees physiological alterations with probable implication also on microbiome functionality. Honeybees show symbiotic interactions with specific gut bacteria that can enhance the adult host performances. Among the known mechanisms, the modulation of the immune system, the degradation of recalcitrant secondary plant metabolites, pollen digestion, and hormonal signaling, are the most important functional benefits for the host honeybee. To date, few research efforts have aimed at revealing the impact of PPP on the gut microbial community of managed and wild honeybees. The majority of the existing literature relays on cage or semifield tests of short duration for research investigating neonicotinoids-gut microbiome interactions. This research wanted to unravel the impact of two neonicotinoids (i.e. imidacloprid and thiacloprid) in natural field conditions up to 5 weeks of exposure. A long-term impact of neonicotinoids on gut microbial community of honeybees was observed. The alterations affected several microbial genera and species such as Frischella spp., lactobacilli and bifidobacteria, whose shifting is implicated in intestinal dysbiosis. Long-term impact leading to dysbiosis was detected in case of exposure to imidacloprid, whereas thiacloprid exposure stimulated temporary dysbiosis. Moreover, the microbial diversity was significantly reduced in neonicotinoid-treated groups. Overall, the reported results support a compromised functionality of the gut microbial community, that might reflect a lower efficiency in the ecosystemic functionality of honeybees.

Background & Aims The electrocardiographic QT interval frequently is prolonged in patients with cirrhosis. Acute gastrointestinal bleeding further prolongs corrected QT (QTc) in patients with cirrhosis, which has been associated with an increased risk of death within 6 weeks. We aimed to confirm these findings and develop a mortality risk index that incorporates QTc. Methods We collected data from 274 patients with cirrhosis and acute gastrointestinal bleeding from any cause admitted to a hospital in Bologna, Italy, from January 2001 through December 2012 (training set). We used logistic regression analysis to identify patient factors associated with death within 6 weeks (6-week mortality). We validated our findings by using data from 200 patients with cirrhosis and gastrointestinal bleeding treated at 2 separate hospitals in Italy, from 2001 through 2016 and 2007 through 2012. Our primary aim was to confirm the prognostic effects of prolonged QTc in a large population of patients and develop a 6-week mortality risk score for acute gastrointestinal bleeding from any cause that incorporates the QTc interval. Results In the training set, QTc greater than 456 ms, the model for end-stage liver disease-sodium (MELD-Na) score, previous bleeding, and serum albumin concentration were associated independently with 6-week mortality. We combined these parameters to create a risk scoring system that we named MELD-Na acute gastrointestinal bleeding (MELDNa-AGIB). In the validation set, the MELDNa-AGIB identified patients who died within 6 weeks with an area under the receiver operating characteristic curve (AUROC) of 0.888; this value was higher than that of the MELD score (AUROC, 0.838; P = .031), MELD score with updated calibration (AUROC, 0.837; P = .029), Child–Turcotte–Pugh score (AUROC, 0.789; P = .004), D'Amico score (AUROC, 0.761; P = .003), and Augustin score (AUROC, 0.792; P = .001), with a net reclassification improvement better than the MELD-Na score (0.266; P = .045). In calibration, the MELDNa-AGIB produced a high score in the Hosmer–Lemeshow test (P = .947), which was superior to that of MELD-Na (P = .146). In the training set, only 6.3% of patients with MELDNa-AGIB scores of 4 or less died within 6 weeks. Among patients with a scores of 9, 16, and 25 or higher, 15.5%, 41.5%, and 81% or more patients died within 6 weeks, respectively. The probability of survival progressively and significantly decreased with increasing scores in the training and validation sets. Conclusions We confirmed QTc as an independent predictor of 6-week mortality in a large population of patients with cirrhosis and acute gastrointestinal bleeding. The combination of QTc, MELD-Na, previous bleeding, and serum albumin (the MELDNa-AGIB score) accurately determines the risk of 6-week mortality, providing timely identification of patients at very high risk of death.

Background and Aims Adventitious roots (ARs) are essential for vegetative propagation. The Arabidopsis thaliana transcription factors SHORT ROOT (SHR) and SCARECROW (SCR) affect primary/lateral root development, but their involvement in AR formation is uncertain. LAX3 and AUX1 auxin influx carriers contribute to primary/ lateral root development. LAX3 expression is regulated by SHR, and LAX3 contributes to AR tip auxin maximum. In contrast, AUX1 involvement in AR development is unknown. Xylogenesis is induced by auxin plus cytokinin as is AR formation, but the genes involved are largely unknown. Stem thin cell layers (TCLs) form ARs and undergo xylogenesis under the same auxin plus cytokinin input. The aim of this research was to investigate SHR, SCR, AUX1 and LAX3 involvement in AR formation and xylogenesis in intact hypocotyls and stem TCLs in arabidopsis. Methods Hypocotyls of scr-1, shr-1, lax3, aux1-21 and lax3/aux1-21 Arabidopsis thaliana null mutant seedlings grown with or without auxin plus cytokinin were examined histologically, as were stem TCLs cultured with auxin plus cytokinin. SCR and AUX1 expression was monitored using pSCR::GFP and AUX1::GUS lines, and LAX3 expression and auxin localization during xylogenesis were monitored by using LAX3::GUS and DR5::GUS lines. Key Results AR formation was inhibited in all mutants, except lax3. SCR was expressed in pericycle anticlinally derived AR-forming cells of intact hypocotyls, and in cell clumps forming AR meristemoids of TCLs. The apex was anomalous in shr and scr ARs. In all mutant hypocotyls, the pericycle divided periclinally to produce xylogenesis. Xylary element maturation was favoured by auxin plus cytokinin in shr and aux1-21. Xylogenesis was enhanced in TCLs, and in aux1-21 and shr in particular. AUX1 was expressed before LAX3, i.e. in the early derivatives leading to either ARs or xylogenesis. Conclusions AR formation and xylogenesis are developmental programmes that are inversely related, but they involve fine-tuning by the same proteins, namely SHR, SCR and AUX1. Pericycle activity is central for the equilibrium between xylary development and AR formation in the hypocotyl, with a role for AUX1 in switching between, and balancing of, the two developmental programmes.