Grime’s CSR classification of functional strategies in terms of competitors, stress-tolerators and ruderals provides a helpful framework for understanding and predicting vegetation responses to ...environmental changes. To evaluate the importance of alternative processes that structure plant communities, it is useful to disentangle the community functional variation into interspecific and intraspecific components and assess their degree of co-variation. Few efforts have been made to investigate the habitat filtering theory in all the interspecific and intraspecific components of a plant community. We hypothesized that under intense climatic conditions, such as drought and cold, functional diversity would decrease towards the dominance of stress tolerant strategies, and that such trends would be reinforced by similar variation at the intraspecific level. We investigated the effect of climatic variation on functional diversity and on community-weighted mean along an elevation gradient in central Italy that ranges from dry and warm climatic conditions at lower elevation to cold and moist ones at higher elevation. We ran regression models to disentangle the total community components for both functional diversity and community-weighted mean into interspecific effect, intraspecific effect and their covariation along the climatic gradient. Our observations were in line with the theory of habitat filtering: we found lower diversity of the Grime strategy for species at both warmer and colder climatic conditions, with dominance of the stress-tolerant strategy. Similarly, the intraspecific effect was lower in cold conditions but higher under drier conditions, which seems to indicate that different processes act at the level of individuals. Given the important intraspecific variability observed in this study, it can be proposed that investigations of vegetation communities should take the role of intraspecific variability into greater consideration.
•Intraspecific trait variability plays a key role in community assembly processes.•Warm conditions enhance intraspecific trait variability.•Cold conditions filter both interspecific and intraspecific trait variability.•Contrasting processes act on inter- and intraspecific trait variability.
Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines ...incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix
) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology.
Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly ...reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters.
Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% hazard ratio 0.97 (0.95-0.99), P < 0.05 and pHRR% hazard ratio 0.977 (0.961-0.993), P < 0.01 were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome.
The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.
We provide experimental evidence for interatomic Coulombic decay (ICD) in mixed rare gas dimers following resonant Auger decay. A velocity map imaging apparatus together with a cooled supersonic beam ...containing Ar2 and NeAr dimers was used to record the energy and angular distributions of electrons in coincidence with two mass selected ions following the excitation of a number of resonances converging to the Ar 2p3/2 –1 threshold using synchrotron radiation. It is shown that the ICD process can be controlled by the choice of the partner atom in the dimer or of the resonance that triggers the resonant Auger decay.
BackgroundClinical response to MAPK inhibitors in metastatic melanoma patients is heterogeneous for reasons still needing to be elucidated. As the patient immune activity contributes to treatment ...clinical benefit, the pre-existing level of immunity at tumor site may provide biomarkers of disease outcome to therapy. Here we investigated whether assessing the density and spatial tissue distribution of key immune cells in the tumor microenvironment could identify patients predisposed to respond to MAPK inhibitors.MethodsPretreatment tumor biopsies from a total of 213 patients (158 for the training set and 55 for the validation set) treated with BRAF or BRAF/MEK inhibitors within the Italian Melanoma Intergroup were stained with selected immune markers (CD8, CD163, β-catenin, PD-L1, PD-L2). Results, obtained by blinded immunohistochemical scoring and digital image analysis, were correlated with clinical response and outcome by multivariate logistic models on response to treatment and clinical outcome, adjusted for American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment received.ResultsPatients with high intratumoral, but not peritumoral, CD8+ T cells and concomitantly low CD163+ myeloid cells displayed higher probability of response (OR 9.91, 95% CI 2.23–44.0, p = 0.003) and longer overall survival (HR 0.34, 95% CI 0.16–0.72, p = 0.005) compared to those with intratumoral low CD8+ T cells and high CD163+ myeloid cells. The latter phenotype was instead associated with a shorter progression free survival (p = 0.010). In contrast, PD-L1 and PD-L2 did not correlate with clinical outcome while tumor β-catenin overexpression showed association with lower probability of response (OR 0.48, 95% CI 0.21–1.06, p = 0.068).ConclusionsAnalysis of the spatially constrained distribution of CD8+ and CD163+ cells, representative of the opposite circuits of antitumor vs protumor immunity, respectively, may assist in identifying melanoma patients with improved response and better outcome upon treatment with MAPK inhibitors. These data underline the role of endogenous immune microenvironment in predisposing metastatic melanoma patients to benefit from therapies targeting driver-oncogenic pathways.
Heat pumps driven by sustainable electricity sources have been identified as a technology that can contribute to reduce carbon dioxide emissions. Furthermore, a heat pump can also provide energy ...savings when combined with a thermal energy storage system. Heat pumps can optimize their efficiency by accumulating thermal energy during periods of lower electricity demand, resulting in shorter operational durations and decreased overall energy consumption. In this work, the combination of a latent heat storage system with an air-water heat pump has been numerically analysed and experimentally tested. A phase change material (PCM) heat exchanger with an immersed plate was designed using a 3D CFD model (COMSOL Multiphysics®). The heat exchanger configuration with six steel plates immersed in the phase change material tank was proposed to enhance heat transfer in the storage system. The developed model is validated against experimental data from a real case study, demonstrating a maximum error of approximately 3% during the discharging phase. Additionally, the study explores the effects of different inlet heat transfer fluid temperatures and flow rates on the PCM solidification time.
The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count ...(AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.
Software updates reduce the opportunity for exploitation. However, since updates can also introduce breaking changes, enterprises face the problem of balancing the need to secure software with ...updates with the need to support operations. We propose a methodology to quantitatively investigate the effectiveness of software updates strategies against attacks of Advanced Persistent Threats (APTs). We consider strategies where the vendor updates are the only limiting factors to cases in which enterprises delay updates from 1 to 7 months based on SANS data. Our manually curated dataset of APT attacks covers 86 APTs and 350 campaigns from 2008 to 2020. It includes information about attack vectors, exploited vulnerabilities (e.g., 0-days versus public vulnerabilities), and affected software and versions. Contrary to common belief, most APT campaigns employed publicly known vulnerabilities. If an enterprise could theoretically update as soon as an update is released, it would face lower odds of being compromised than those waiting one (4.9x) or three (9.1x) months. However, if attacked, it could still be compromised from 14% to 33% of the times. As in practice enterprises must do regression testing before applying an update, our major finding is that one could perform 12% of all possible updates restricting oneself only to versions fixing publicly known vulnerabilities without significant changes to the odds of being compromised compared to a company that updates for all versions.
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