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The article describes the main achievements of the NUMEN project together with an updated and detailed overview of the related R&D activities and theoretical developments. NUMEN proposes an ...innovative technique to access the nuclear matrix elements entering the expression of the lifetime of the double beta decay by cross section measurements of heavy-ion induced Double Charge Exchange (DCE) reactions. Despite the fact that the two processes, namely neutrinoless double beta decay and DCE reactions, are triggered by the weak and strong interaction respectively, important analogies are suggested. The basic point is the coincidence of the initial and final state many-body wave functions in the two types of processes and the formal similarity of the transition operators. First experimental results obtained at the INFN-LNS laboratory for the
40
Ca(
18
O,
18
Ne)
40
Ar reaction at 270MeV give an encouraging indication on the capability of the proposed technique to access relevant quantitative information. The main experimental tools for this project are the K800 Superconducting Cyclotron and MAGNEX spectrometer. The former is used for the acceleration of the required high resolution and low emittance heavy-ion beams and the latter is the large acceptance magnetic spectrometer for the detection of the ejectiles. The use of the high-order trajectory reconstruction technique, implemented in MAGNEX, allows to reach the experimental resolution and sensitivity required for the accurate measurement of the DCE cross sections at forward angles. However, the tiny values of such cross sections and the resolution requirements demand beam intensities much larger than those manageable with the present facility. The on-going upgrade of the INFN-LNS facilities in this perspective is part of the NUMEN project and will be discussed in the article.
Coniferous forests contribute to the European economy; however, they have experienced a decline since the late 1990s due to an invasive pest known as the pine processionary moth, Thaumetopoea ...pityocampa. The impacts of this pest are increasingly exacerbated by climate change. Traditional control strategies involving pesticides have had negative effects on public health and the environment. Instead, forest managers seek a more ecological and sustainable approach to management that promotes the natural actions of pest control agents. This study aims to evaluate the role of bats in suppressing pine processionary moths in pine forests and examine how the bat community composition and abundance influence pest consumption. Bats were sampled in the mountainous environment of the Serra da Estrela in central Portugal to collect faecal samples for DNA meta-barcoding analysis. We assessed the relationship between a) bat richness, b) bat relative abundance, c) bat diet richness, and the frequency of pine processionary moth consumption. Our findings indicate that sites with the highest bat species richness and abundance exhibit the highest levels of pine processionary moth consumption. The intensity of pine processionary moth consumption is independent of insect diversity within the site. The highest occurrence of pine processionary moth presence in bat diets is primarily observed in species that forage in cluttered habitats. A typical predator of pine processionary moths among bats is likely to be a forest-dwelling species that specialises in consuming Lepidoptera. These species primarily use short-range echolocation calls, which are relatively inaudible to tympanate moths, suitable for locating prey in cluttered environments, employing a gleaning hunting strategy. Examples include species from the genera Plecotus, Myotis, and Rhinolophus. This study enhances our understanding of the potential pest consumption services provided by bats in pine forests. The insights gained from this research can inform integrated pest management practices in forestry.
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•Unveiled new PPM bat predators, emphasizing bats' pest suppression role•Cluttered and open space foragers: bat guilds with high pest consumption potential•Bat abundance, species richness and bat diet richness link with pest consumption.•Diverse bat communities enhance pest consumption, reinforcing biotic resistance.•Niche segregation fosters bat coexistence, enhancing ecosystem stability
Immunotherapy combined with chemotherapy significantly improves progression-free survival (PFS) compared to first-line chemotherapy alone in advanced endometrial cancer (EC), with a much larger ...effect size in microsatellite instability-high (MSI-H) cases. New biomarkers might help to select patients who may have benefit among those with a microsatellite-stable (MSS) tumor.
In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab.
Out of 125 randomized patients, 109 had samples eligible for next-generation sequencing analysis, and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA), there were 29 cases with MSI-H, 26 with MSS TP53 wild type (wt), 47 with MSS TP53 mutated (mut), and 1 case with POLE mutation. Four mutated genes were present in >30% of cases: TP53, PIK3CA, ARID1A, and PTEN. Eleven patients (10%) had a BRCA1/2 mutation (five in MSI-H and six in MSS). High tumor mutational burden (≥10 muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53 mut, and no case in the MSS/TP53 wt category. The effect of avelumab on PFS significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53 mut (P interaction = 0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, which was better in the presence of the mutation (ARID1A P interaction = 0.01; PTEN P interaction = 0.002).
The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced EC.
Abstract Ghrelin and ghrelin receptor agonist have effects on central neurons in many locations, including the hypothalamus, caudal brain stem, and spinal cord. However, descriptions of the ...distributions of ghrelin-like immunoreactivity in the CNS in published work are inconsistent. We have used three well-characterized anti-ghrelin antibodies, an antibody to the unacylated form of ghrelin, and a ghrelin peptide assay in rats, mice, ghrelin knockout mice, and ghrelin receptor reporter mice to re-evaluate ghrelin presence in the rodent CNS. The stomach served as a positive control. All antibodies were effective in revealing gastric endocrine cells. However, no specific staining could be found in the brain or spinal cord. Concentrations of antibody 10 to 30 times those effective in the stomach bound to nerve cells in rat and mouse brain, but this binding was not reduced by absorbing concentrations of ghrelin peptide, or by use of ghrelin gene knockout mice. Concentrations of ghrelin-like peptide, detected by enzyme-linked immunosorbent assay in extracts of hypothalamus, were 1% of gastric concentrations. Ghrelin receptor-expressing neurons had no adjacent ghrelin immunoreactive terminals. It is concluded that there are insignificant amounts of authentic ghrelin in neurons in the mouse or rat CNS and that ghrelin receptor-expressing neurons do not receive synaptic inputs from ghrelin-immunoreactive nerve terminals in these species.
Abstract Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased ...risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance < 25 ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15–49 ml/min) and those on dialysis.
Traditional farming, where livestock is seasonally managed as free ranging and the use of drugs is reduced or absent, may prove beneficial to biodiversity by fostering the occurrence of spatial ...heterogeneity, and increasing the availability of trophic resources to wildlife. Previous work indicates that the presence of cattle in lowlands leads to an increase in bat foraging activity, yet no study has addressed this topic in mountainous regions, where free-ranging livestock is still common. Here we explore the relationships between landscape structure, farming and bat activity in a mountainous agricultural area, hypothesizing that bat activity will increase in response to the presence of livestock and landscape structure and heterogeneity. We found that traditional cattle farming may have a role in influencing bat activity in mountainous agroecosystems, yet its effects are evident for a limited number of species. Three pipistrelle species favoured foraging in areas subjected to cattle farming by hunting more often over cattle or fresh dung than at control sites. Free-ranging cattle thus provide profitable foraging opportunities for bats in mountainous landscapes, which remarks the importance of traditional farming activities in sustaining biodiversity. Cattle might also benefit from bat foraging activity if this leads to suppression of blood-sucking pests.
The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more ...aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.
To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period.
Young adults (YAs: 18–29 years old) significantly differed from adults (30–59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011).
The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.
NCT00510926, NCT00514488, NCT00769327, NCT00481052.
There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS.
We ...conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32+/-7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53+/-8 versus 52+/-9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group).
Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.
Purpose
Aim of this study was to evaluate the association between body mass index (BMI) and aggressive features of differentiated thyroid cancer (DTC) in a prospective cohort.
Methods
Patients with ...DTC were prospectively enrolled at a tertiary referral center and grouped according to their BMI. Aggressive clinic-pathological features were analyzed following the American Thyroid Association Initial Risk Stratification System score.
Results
The cohort was composed of 432 patients: 5 (1.2%) were underweight, 187 (43.3%) normal weight, 154 (35.6%) overweight, 68 (15.7%) grade 1 obese, 11 (2.5%) grade 2 obese and 7 (1.6%) grade 3 obese. No single feature of advanced thyroid cancer was more frequent in obese patients than in others. No significant correlation was found between BMI, primary tumor size (Spearman’s
ρ
− 0.02;
p
= 0.71) and ATA Initial Risk Stratification System score (
ρ
0.03;
p
= 0.49), after adjustment for age. According to the multivariate logistic regression analysis, male gender and pre-surgical diagnosis of cancer were significant predictors of cancer with high or intermediate–high recurrence risk according to the ATA system (OR 2.06 and 2.51, respectively), while older age at diagnosis was a protective factor (OR 0.98), and BMI was not a predictor. BMI was a predictor of microscopic extrathyroidal extension only (OR 1.06).
Conclusions
Obesity was not associated with aggressive features in this prospective, European cohort of patients with DTC.
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