This paper proposes a new algorithm to estimate the maximum likelihood parameters of an Epidemic Type Aftershock Sequences (ETAS) model. It is based on Simulated Annealing, a versatile method that ...solves problems of global optimization and ensures convergence to a global optimum. The procedure is tested on both simulated and real catalogs. The main conclusion is that the method performs poorly as the size of the catalog decreases because the effect of the correlation of the ETAS parameters is more significant. These results give new insights into the ETAS model and the efficiency of the maximum-likelihood method within this context.
We describe the results of a prospective, real‐time earthquake forecast experiment made during a seismic emergency. A Mw 6.3 earthquake struck the city of L'Aquila, Italy on April 6, 2009, causing ...hundreds of deaths and vast damage. Immediately following this event, we began producing daily earthquake forecasts for the region, and we provided these forecasts to Civil Protection – the agency responsible for managing the emergency. The forecasts are based on a stochastic model that combines the Gutenberg‐Richter distribution of earthquake magnitudes and power‐law decay in space and time of triggered earthquakes. The results from the first month following the L'Aquila earthquake exhibit a good fit between forecasts and observations, indicating that accurate earthquake forecasting is now a realistic goal. Our experience with this experiment demonstrates an urgent need for a connection between probabilistic forecasts and decision‐making in order to establish – before crises – quantitative and transparent protocols for decision support.
Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, ...multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control;
=145) or walking exercise (
=151); 227 patients (exercise
=104; control
=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m;
<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds;
=0.001 between groups). The cognitive function score (
=0.04) and quality of social interaction score (
=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.
Dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD ...onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.
SUMMARY
This study presents a new robust statistical framework, in which to measure relative differences, or deviations from a hypothetical reference value, of Gutenberg–Richter b-value. Moreover, it ...applies this method to recent seismicity in Italy, to find possible changes of earthquake magnitude distribution in time and space. The method uses bootstrap techniques, which have no prior assumptions about the distribution of data, keeping their basic features. Excluding Central Italy, no significative b-value variation is found, revealing that the frequency–magnitude distribution exponent is substantially stable or that data are not able to reveal hidden variations. Considering the small size of examined magnitude samples, we cannot definitively decide if the higher b-values in Central Italy, consistently founded by all applied tests, have a physical origin or result from a statistical bias. In any case, they indicate short-lived excursions which have a temporary nature and, therefore, cannot be associated solely to spatial variations in tectonic framework. Both the methodological issues and the results of the application to seismicity in Italy show that a correct assessing of b-value changes requests appropriate statistics, that accurately quantify the low accuracy and precision of b-value estimation for small magnitude samples.
The purpose of this work is to put forward a double branching model to describe the spatiotemporal earthquake occurrence. The model, applied to two worldwide catalogs in different time‐magnitude ...windows, shows a good fit to the data, and its earthquake forecasting performances are superior to what was obtained by the ETAS (first‐step branching model) and by the Poisson model. The results obtained also provide interesting insights about the physics of the earthquake generation process and the time evolution of seismicity. In particular, the so‐called background seismicity, i.e., the catalog after removing short‐time clustered events, is described by a further (second‐step model) branching characterized by a longer time‐space clustering that may be due to long‐term seismic interaction. Notably, this branching highlights a long‐term temporal evolution of the seismicity that is never taken into account in seismic hazard assessment or in the definition of reference seismicity models for a large earthquake occurrence. Another interesting issue is related to the parameters of the short‐term clustering that appear constant in a different magnitude window, supporting some sort of universality for the generating process.
Many
Trichoderma
spp. are successful plant beneficial microbial inoculants due to their ability to act as biocontrol agents with direct antagonistic activities to phytopathogens, and as biostimulants ...capable of promoting plant growth. This work investigated the effects of treatments with three selected
Trichoderma
strains (T22, TH1, and GV41) to strawberry plants on the productivity, metabolites and proteome of the formed fruits.
Trichoderma
applications stimulated plant growth, increased strawberry fruit yield, and favored selective accumulation of anthocyanins and other antioxidants in red ripened fruits. Proteomic analysis of fruits harvested from the plants previously treated with
Trichoderma
demonstrated that the microbial inoculants highly affected the representation of proteins associated with responses to stress/external stimuli, nutrient uptake, protein metabolism, carbon/energy metabolism and secondary metabolism, also providing a possible explanation to the presence of specific metabolites in fruits. Bioinformatic analysis of these differential proteins revealed a central network of interacting molecular species, providing a rationale to the concomitant modulation of different plant physiological processes following the microbial inoculation. These findings indicated that the application of
Trichoderma
-based products exerts a positive impact on strawberry, integrating well with previous observations on the molecular mechanisms activated in roots and leaves of other tested plant species, demonstrating that the efficacy of using a biological approach with beneficial microbes on the maturing plant is also able to transfer advantages to the developing fruits.
The mortality from esophageal variceal hemorrhage in liver cirrhosis patients remains approximately 15-20%. Predictors of short-term outcomes, such as the hepatic venous pressure gradient, are often ...unavailable in the acute setting. Clinical variables seem to have a similar predictive performance, but some variables including active bleeding during endoscopy have not been reevaluated after the utilization of endoscopic banding as endoscopic procedure. In addition, patients with severe liver failure are often excluded from clinical trials. The aim of this study was to prospectively reevaluate the risk factors affecting a 5-day failure after acute variceal bleeding in unselected cirrhotic patients, managed with the current standard treatment using vasoactive drugs, band ligation, and antibiotics.
One hundred and eighty five patients with liver cirrhosis and variceal bleeding admitted from January 2010 to July 2011 were evaluated.
Hepatocellular carcinoma was present in 28.1% of cases and portal vein thrombosis (PVT) was present in 17.3% of cases. Band ligation was feasible in 92.4% of cases. Five-day failure occurred in 16.8% of cases; 12 patients (6.5%) experienced failure to control bleeding or early rebleeding, and 66.7% of patients died within 5 days. The overall 5-day mortality rate was 14.6%. By multivariate analysis, we determined that Child-Pugh class C, a white blood cell count over 10 × 10(9)/l, and the presence of PVT were the only independent predictors of the 5-day failure.
The prognosis of a consistent group of liver cirrhosis patients with variceal bleeding remains poor. The current treatment is highly effective in controlling variceal bleeding, but mortality is related mainly to the severity of liver failure.
Severe asthma is a disease with a heavy socio-economic burden and a relevant impact on the life of patients. Mepolizumab (MEP) was recently introduced in practice. The previous data were favourable ...as efficacy and safety are concerned. Nowadays, we can report the clinical data after more than one year of use of MEP in the real-life setting.
To evaluate the efficacy and safety of MEP in a real life framework, mainly concerning asthma exacerbations, steroid dependence, effects on respiratory function and adverse events.
This retrospective analysis was performed on 138 patients, treated with MEP for at least 12 months, and referred to eleven severe asthma clinics in Italy. All patients met the criteria for severe uncontrolled asthma according to ATS/ERS guidelines and prescribing MEP conditions according to the Italian Drug Agency (AIFA).
We could observe 138 patients (78 female, age 58 ± 10 years). The average age of onset of asthma was 34 ± 16 years. The blood eosinophil count decreased from 822 ± 491/μL at baseline to 117 ± 96/μL (p < .0001) after 12 months of therapy. Exacerbations decreased from 3.8/year to 0.7/year (−81%; p < .0001). Steroid-dependent patients before MEP (80%) with a daily dose of 10.1 ± 9.4 mg prednisone decrease at 28% after 12 months with a mean of 2.0 ± 4.2 mg/day (p < .0001). The occurrence of adverse events was overall low.
In this real-life setting, MEP confirmed its efficacy and safety profile, already shown in clinical trials. This was apparent concerning exacerbation rate, systemic steroids intake and safety.
Hypoxia-inducible factor-1α (HIF-1α), a central player in maintaining gut-microbiota homeostasis, plays a pivotal role in inducing adaptive mechanisms to hypoxia and is negatively regulated by prolyl ...hydroxylase 2 (PHD2). HIF-1α is stabilized through PI3K/AKT signaling regardless of oxygen levels. Considering the crucial role of the HIF pathway in intestinal mucosal physiology and its relationships with gut microbiota, this study aimed to evaluate the ability of the lysate from the multi-strain probiotic formulation SLAB51 to affect the HIF pathway in a model of in vitro human intestinal epithelium (intestinal epithelial cells, IECs) and to protect from lipopolysaccharide (LPS) challenge. The exposure of IECs to SLAB51 lysate under normoxic conditions led to a dose-dependent increase in HIF-1α protein levels, which was associated with higher glycolytic metabolism and L-lactate production. Probiotic lysate significantly reduced PHD2 levels and HIF-1α hydroxylation, thus leading to HIF-1α stabilization. The ability of SLAB51 lysate to increase HIF-1α levels was also associated with the activation of the PI3K/AKT pathway and with the inhibition of NF-κB, nitric oxide synthase 2 (NOS2), and IL-1β increase elicited by LPS treatment. Our results suggest that the probiotic treatment, by stabilizing HIF-1α, can protect from an LPS-induced inflammatory response through a mechanism involving PI3K/AKT signaling.
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