Post-Newtonian evolution of massive black hole triplets in galactic nuclei - IV. Implications for LISA

Coalescing massive black hole binaries (MBHBs) of 10(4-7) M-circle dot, forming in the aftermath of galaxy mergers, are primary targets of the space mission LISA, the Laser Interferometer Space Antenna. An assessment of LISA detection prospects requires an estimate of the abundance and properties of MBHBs that form and evolve during the assembly of cosmic structures. To this aim, we employ a semi-analytic model to follow the co-evolution of MBHBs within their host galaxies. We identify three major evolutionary channels driving the binaries to coalescence: two standard paths along which the binary evolution is driven by interactions with the stellar and/or gaseous environment, and a novel channel where MBHB coalescence occurs during the interaction with a third black hole. For each channel, we follow the orbital evolution ofMBHBs with physically motivated models that include a self-consistent treatment of the orbital eccentricity. We find that LISA will detect between approximate to 25 and approximate to 75 events per year depending on the seed model. We show that triple-induced coalescences can range from a few detected events up to similar to 30 per cent of the total detected mergers. Moreover, even if the standard gas/stars-driven evolutionary channels should fail and MBHBs were to stall, triple interactions would still occur as a result of the hierarchical nature of galaxy formation, resulting in about approximate to 10 to approximate to 20 LISA detections per year. Remarkably, triple interactions among the black holes can produce coalescing binaries with large eccentricities (greater than or similar to 0.9) upon entrance into the LISA band. This eccentricity will remain significant (similar to 0.1) also at merger, requiring suitable templates for parameter estimation. Keyword

Expression of Autophagic and Inflammatory Markers in Normal Mucosa of Individuals with Colorectal Adenomas: A Cross Sectional Study among Italian Outpatients Undergoing Colonoscopy

: Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer may reach 6% of the population living in developed countries. In the current era of personalized medicine, CRC is no longer considered as a single entity. In more recent years many studies have described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site. The aim of our study is to assess in a multidimensional model the association between metabolic status and inflammatory and autophagic changes in the normal colorectal mucosa classified as right-sided, left-sided and rectum, and the presence of adenomas. One hundred and sixteen patients undergoing colonoscopy were recruited and underwent a complete serum lipid profile, immunofluorescence analysis of colonic biopsies for MAPLC3 and myeloperoxidase expression, matched with clinical and anthropometric characteristics. Presence of adenomas correlated with cholesterol (total and LDL) levels, IL-6 levels, and MAPLC3 tissue expression, especially in the right colon. In conclusion, serum IL-6 amount and autophagic markers could be good predictors of the presence of colorectal adenomas

Attenuated polyposis of the large bowel: a morphologic and molecular approach

Attenuated polyposis could be defined as a variant of familial adenomatous polyposis (FAP) in which synchronous polyps of the large bowel range between 10 and 99. We analysed all cases of attenuated polyposis observed over the last 30 years with the objectives: (A) to classify the disease according to different type and proportion of polyps; (B) To ascertain the contribution of APC and MutYH genes; (C) to discover features which could arise the suspicion of mutations; (D) To obtain indications for management and follow-up. 84 individuals in 82 families were studied. Polyps were classified into four groups as adenoma, hyperplastic, other serrated lesions or others; APC and MutYH mutations were assessed. Mean age at diagnosis was 54 ± 14 years in men and 48 ± 13 in women (P = 0.005). Polyps were more numerous in women (37 ± 26 vs 29 ± 22). Sixty % of patients underwent bowel resection, mainly for cancer; the remaining were managed through endoscopy. A total of 2586 polyps were detected at diagnostic endoscopy: 2026 (80 %) were removed and analysed. Adenomas were diagnosed in 1445 (70 %), hyperplastic polyps in 541 (26 %), other serrated lesions in 61 (2.9 %). Adenomas and hyperplastic lesions were detected in the majority of patients. In 68 patients (81 %) in whom studies were executed, APC mutations were found in 8 and MutYH mutations in 10. Genetic variants were more frequent in women (12 vs 6, P = 0.039). Taking into consideration the prevalent (>50 %) histology and presence of mutations, patients could be subdivided into four groups: (1) APC mutated polyposis (AFAP), when adenomas were >50 % and APC mutations detected (no. 8, 10 %); (2) MutYH mutated polyposis (MAP), adenomas >50 % and biallelic MutYH mutations (no. 10, 12 %); (1) attenuated polyposis without detectable mutations, prevalence of adenomas, 48 cases (57 %); (1) hyperplastic-serrated polyposis, with prevalence (>50 %) of hyperplastic/other serrated lesions and no constitutional mutation (no. 18, 21 %). Aggregation of tumors, cancer in probands, distribution of polyps and other clinical characteristics showed no difference among the four groups. In conclusions, AFAP and MAP, the polyposis labeled by constitutional mutations, represented about 25 % of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex

Burnout precursors in oncology nurses: A preliminary cross-sectional study with a systemic organizational analysis

Burnout negatively affects nurses' health and performance. Healthcare managers have an ethical duty to create healthy organizations that reduce burnout, especially within critical settings such as oncology. The aim of this study was twofold: (1) to measure the presence of nurses' burnout to formulate organizational strategies to prevent the syndrome onset, and (2) to evaluate the effect of recent organizational changes on the burnout phenomenon. A descriptive, cross-sectional design supported by a systemic organizational analysis was conducted in a Swiss Oncology Institute in 2013. Of 103 nurses working in the Institute, 52 (51.4%) completed the Burnout Potential Inventory (BPI) questionnaire. Data were analyzed using descriptive statistics and Mann-Whitney and Kruskal-Wallis tests. Burnout risk levels were low to moderate. Only 2 nurses out of the 52 showed moderate burnout risk levels. Inpatient nurses showed a higher risk of burnout than outpatient nurses, particularly due to ambiguity and feelings of powerlessness. Nurses with post-basic education showed a higher risk when considering poor teamwork values and ambiguity in the workplace. Poor middle-management was found to negatively influence worker wellbeing. The working environment set by management resulted in low burnout risk levels. Managers must carefully select middle-management because inappropriate leadership might promote the onset of burnout

Aberrant DNA methylation profiles of inherited and sporadic colorectal cancer

Background: Aberrant DNA methylation has been widely investigated in sporadic colorectal carcinomas (CRCs), and extensive work has been performed to characterize different methylation profiles of CRC. Less information is available about the role of epigenetics in hereditary CRC and about the possible clinical use of epigenetic biomarkers in CRC, regardless of the etiopathogenesis. Long interspersed nucleotide element 1 (LINE-1) hypomethylation and gene-specific hypermethylation of 38 promoters were analyzed in multicenter series of 220 CRCs including 71 Lynch (Lynch colorectal cancer with microsatellite instability (LS-MSI)), 23 CRCs of patients under 40 years in which the main inherited CRC syndromes had been excluded (early-onset colorectal cancer with microsatellite stability (EO-MSS)), and 126 sporadic CRCs, comprising 28 cases with microsatellite instability (S-MSI) and 98 that were microsatellite stable (S-MSS). All tumor methylation patterns were integrated with clinicopathological and genetic characteristics, namely chromosomal instability (CIN), TP53 loss, BRAF, and KRAS mutations. Results: LS-MSI mainly showed absence of extensive DNA hypo-and hypermethylation. LINE-1 hypomethylation was observed in a subset of LS-MSI that were associated with the worse prognosis. Genetically, they commonly displayed G:A transition in the KRAS gene and absence of a CIN phenotype and of TP53 loss. S-MSI exhibited a specific epigenetic profile showing low rates of LINE-1 hypomethylation and extensive gene hypermethylation. S-MSI were mainly characterized by MLH1 methylation, BRAF mutation, and absence of a CIN phenotype and of TP53 loss. By contrast, S-MSS showed a high frequency of LINE-1 hypomethylation and of CIN, and they were associated with a worse prognosis. EO-MSS were a genetically and epigenetically heterogeneous group of CRCs. Like LS-MSI, some EO-MSS displayed low rates of DNA hypo-or hypermethylation and frequent G:A transitions in the KRAS gene, suggesting that a genetic syndrome might still be unrevealed in these patients. By contrast, some EO-MSS showed similar features to those observed in S-MSS, such as LINE-1 hypomethylation, CIN, and TP53 deletion. In all four classes, hypermethylation of ESR1, GATA5, and WT1 was very common. Conclusions: Aberrant DNA methylation analysis allows the identification of different subsets of CRCs. This study confirms the potential utility of methylation tests for early detection of CRC and suggests that LINE-1 hypomethylation may be a useful prognostic marker in both sporadic and inherited CRCs

CHE-S® as a tool to predict the Caregiver's ability to actively manage disability of stroke patients admitted to the ward of the complex rehabilitation structure of ASUGI

Introduction: This article affirms that measuring the Caregiver's emotional experience and engagement, especially as the condition of the person assisted changes, is useful for assessing the sustainability of the care plan. Methods: With this pilot study, aimed at detecting the level of Caregiver engagement, by using the Caregiving Engagement Scale (CHE-S®), for people suffering from chronic and/or fragile pathologies, it was decided to verify the relationship between engagement levels and other variables such as: socio-demographic characteristics of the Caregiver; duration and frequency person; clinical characteristics of the assisted person. Results and Conclusions: In the future, the results of this research will allow to define new working practices to support those who take on the responsibility and burden of caring for a sick, fragile, disabled family member

TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m 2, oxaliplatin 85 mg/m 2, L-leucovorin 200 mg/m 2, 5-fluoruracil 2400 mg/m 2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722

Massive Black Hole Binaries as LISA Precursors in the Roman High Latitude Time Domain Survey

With its capacity to observe $\sim 10^{5-6}$ faint active galactic nuclei (AGN) out to redshift $z\approx 6$, Roman is poised to reveal a population of $10^{4-6}\, {\rm M_\odot}$ black holes during an epoch of vigorous galaxy assembly. By measuring the light curves of a subset of these AGN and looking for periodicity, Roman can identify several hundred massive black hole binaries (MBHBs) with 5-12 day orbital periods, which emit copious gravitational radiation and will inevitably merge on timescales of $10^{3-5}$ years. During the last few months of their merger, such binaries are observable with the Laser Interferometer Space Antenna (LISA), a joint ESA/NASA gravitational wave mission set to launch in the mid-2030s. Roman can thus find LISA precursors, provide uniquely robust constraints on the LISA source population, help identify the host galaxies of LISA mergers, and unlock the potential of multi-messenger astrophysics with massive black hole binaries.Comment: White Paper for the Nancy Grace Roman Space Telescope's Core Community Surveys (https://roman.gsfc.nasa.gov/science/ccs_white_papers.html