Five-year follow-up mortality prognostic index for colorectal patients

Purpose: To identify 5-year survival prognostic variables in patients with colorectal cancer (CRC) and to propose a survival prognostic score that also takes into account changes over time in the patient's health-related quality of life (HRQoL) status. Methods: Prospective observational cohort study of CRC patients. We collected data from their diagnosis, intervention, and at 1, 2, 3, and 5 years following the index intervention, also collecting HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariate Cox proportional models were used. Results: We found predictors of mortality over the 5-year follow-up to be being older; being male; having a higher TNM stage; having a higher lymph node ratio; having a result of CRC surgery classified as R1 or R2; invasion of neighboring organs; having a higher score on the Charlson comorbidity index; having an ASA IV; and having worse scores, worse quality of life, on the EORTC and EQ-5D questionnaires, as compared to those with higher scores in each of those questionnaires respectively. Conclusions: These results allow preventive and controlling measures to be established on long-term follow-up of these patients, based on a few easily measurable variables. Implications for cancer survivors: Patients with colorectal cancer should be monitored more closely depending on the severity of their disease and comorbidities as well as the perceived health-related quality of life, and preventive measures should be established to prevent adverse outcomes and therefore to ensure that better treatment is received. Trial registration: ClinicalTrials.gov identifier: NCT02488161Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported in part by grants from the Instituto de Salud Carlos III and the European Regional Development Fund (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397); the Spanish Ministry of the Economy (PID2020-115738 GB-I00); the Departments of Health (2010111098) and Education, Language Policy and Culture (IT1456-22; IT1598-22; IT-1187–19) of the Basque Government; the Research Committee of Galdakao Hospital; the REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas) thematic network of the Instituto de Salud Carlos III; and the Department of Education of the Basque Government through the Consolidated Research Group MATHMODE (IT1456-22) and the Basque Government through BMTF “Mathematical Modeling Applied to Health” Project

A Richness Study of 14 Distant X-ray Clusters From the 160 Square Degree Survey

We have measured the surface density of galaxies toward 14 X-ray-selected cluster candidates at redshifts greater than z=0.46, and we show that they are associated with rich galaxy concentrations. We find that the clusters range between Abell richness classes 0-2, and have a most probable richness class of one. We compare the richness distribution of our distant clusters to those for three samples of nearby clusters with similar X-ray luminosities. We find that the nearby and distant samples have similar richness distributions, which shows that clusters have apparently not evolved substantially in richness since redshift z =0.5. We compare the distribution of distant X-ray clusters in the L_x--richness plane to the distribution of optically-selected clusters from the Palomar Distant Cluster Survey. The optically-selected clusters appear overly rich for their X-ray luminosities when compared to X-ray-selected clusters. Apparently, X-ray and optical surveys do not necessarily sample identical mass concentrations at large redshifts. This may indicate the existence of a population of optically rich clusters with anomalously low X-ray emission. More likely, however, it reflects the tendency for optical surveys to select unvirialized mass concentrations, as might be expected when peering along large-scale filaments.Comment: The abstract has been abridged. Accepted for publication in the Astrophysical Journa

The leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium

Purpose: The aim of this study was to investigate the interaction and co-localization of novel interacting proteins with the Leber congenital amaurosis (LCA) associated protein aryl hydrocarbon receptor interacting protein-like 1 (AIPL1). Methods: The CytoTrapXR yeast two-hybrid system was used to screen a bovine retinal cDNA library. A novel interaction between AIPL1 and members of the family of EB proteins was confirmed by directed yeast two-hybrid analysis and co-immunoprecipitation assays. The localization of AIPL1 and the EB proteins in cultured cells and in retinal cryosections was examined by immunofluorescence microscopy and cryo-immunogold electron microscopy. Results: Yeast two-hybrid (Y2H) analysis identified the interaction between AIPL1 and the EB proteins, EB1 and EB3. EB1 and EB3 were specifically co-immunoprecipitated with AIPL1 from SK-N-SH neuroblastoma cells. In directed 1:1 Y2H analysis, the interaction of EB1 with AIPL1 harbouring the LCA-causing mutations A197P, C239R and W278X was severely compromised. Immunofluorescent confocal microscopy revealed that AIPL1 did not co-localize with endogenous EB1 at the tips of microtubules, endogenous EB1 at the microtu-bule organising centre following disruption of the microtubule network, or with endogenous β-tubulin. Moreover, AIPL1 did not localize to primary cilia in ARPE-19 cells, whereas EB1 co-localized with the centrosomal marker pericentrin at the base of primary cilia. However, both AIPL1 and the EB proteins, EB1 and EB3, co-localized with centrin-3 in the connecting cilium of photoreceptor cells. Cryo-immunogold electron microscopy confirmed the co-localization of AIPL1 and EB1 in the connecting cilia in human retinal photoreceptors. Conclusions: AIPL1 and the EB proteins, EB1 and EB3, localize at the connecting cilia of retinal photore-ceptor cells, but do not co-localize in the cellular microtubule network or in primary cilia in non-retinal cells. These findings suggest that AIPL1 function in these cells is not related to the role of EB proteins in microtubule dynamics or primary ciliogenesis, but that their association may be related to a specific role in the specialized cilia apparatus of retinal photoreceptors

Wnt-11 as a potential prognostic biomarker and therapeutic target in colorectal cancer

The expression of the secreted factor Wnt-11 is elevated in several types of cancer, including colorectal cancer, where it promotes cancer cell migration and invasion. Analysis of colorectal cancer gene expression databases associated WNT11 mRNA expression with increased likelihood of metastasis in a subset of patients. WNT11 expression was correlated with the expression of the Wnt receptors FZD6, RYK, and PTK7, and the combined expression of WNT11, FZD6 and RYK or PTK7 was associated with an increased risk of 5-year mortality rates. Immunohistochemical analysis of Wnt-11 in a cohort of 357 colorectal cancer patients found significantly higher Wnt-11 levels in tumors, compared with benign tissue. Elevated Wnt-11 levels occurred more frequently in rectal tumors than in colonic tumors and in tumors from women than men. In univariate analysis, increased Wnt-11 expression was also associated with tumor invasion and increased 5-year mortality. High Wnt-11 levels were not associated with high levels of nuclear β-catenin, suggesting Wnt-11 is not simply an indicator for activation of β-catenin-dependent signaling. Expression of Wnt-11 in colorectal cancer cell lines expressing low endogenous Wnt-11 inhibited β-catenin/Tcf activity and increased ATF2-dependent transcriptional activity. WNT11 gene silencing and antibody-mediated inhibition of Wnt-11 in colorectal cancer cell lines expressing high Wnt-11 reduced their capacity for invasion. Together, these observations suggest that Wnt-11 could be a potential target for the treatment of patients with invasive colorectal cancer

Statistical Modeling of Single Target Cell Encapsulation

High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems.Wallace H. Coulter Foundation (Young Investigator in Bioengineering Award)National Institutes of Health (U.S.) (Grant R01AI081534)National Institutes of Health (U.S.) (Grant R21AI087107

Investigation into the magnetic properties of CoFeNiCryCux alloys

The search for cheap, corrosion-resistant, thermally-mechanically stable functional magnetic materials, including soft magnetic and magneto-caloric materials has led to research focused on high entropy alloys (HEAs). Previous research shows that alloying elements with negative enthalpies of mixing can facilitate a second-order phase transition. On the other side of the spectrum, compositional segregation cause by positive enthalpy of mixing alloying additions (such as Cu) may also be used to tune magnetic properties. This paper studies the structural, magnetic and magneto-caloric effect of the FCC alloys CoFeNiCryCux (x = 0.0, 0.5, 1.0 and 1.5, y = 0.0, 0.8 and 1.0) to tune these properties with Cu and Cr alloying. Scanning electron microscopy of the compositions show nanoparticles forming within the grains as the Cu concentration increases. Cr addition to CoFeNiCu1.0 has a larger effect on the magnetic and magneto-caloric properties compared to the Cu addition to CoFeNiCr1.0. The addition of Cu (x = 0.5) to CoFeNiCr1.0 improved both the saturation magnetisation and Curie temperature; addition of Cr (y = 1.0) to CoFeNiCu1.0 decreased the Curie temperature by 900 K. All alloys were determined to have a second-order phase transition around their Curie temperature. The refrigerant capacity at 2 T was found to be similar to existing HEAs, although the Curie temperatures were lower than room temperature. Based on this data the CoFeNiCr0.8Cu composition was fabricated to increase the Curie temperature towards 300 K to explore these HEAs as new candidates for room temperature magneto-caloric applications. The fabricated composition showed Curie temperature, saturation magnetisation, and refrigerant capacity increasing with the small reduction in Cr content

Heart rate variability and the relationship between trauma exposure age, and psychopathology in a post-conflict setting

BACKGROUND: Cumulative exposure to potentially traumatic events (PTEs) increases risk for mental distress in conflict-affected settings, but the psychophysiological mechanisms that mediate this dose-response relationship are unknown. We investigated diminished heart rate variability (HRV) - an index of vagus nerve function and a robust predictor of emotion regulation capacity - as a vulnerability marker that potentially mediates the association between PTE exposure, age and symptoms of posttraumatic stress disorder (PTSD), psychological distress and aggressive behavior, in a community sample from Timor-Leste - a post-conflict country with a history of mass violence. METHOD: Resting state heart rate data was recorded from 45 cases of PTSD, depression and intermittent explosive disorder (IED); and 29 non-case controls. RESULTS: Resting HRV was significantly reduced in the combined case group compared with non-cases (p = .021; Cohen's d = 0.5). A significant mediation effect was also observed, whereby a sequence of increased age, reduced HRV and elevated PTSD symptoms mediated the association between PTE exposure and distress (B = .06, SE = .05, 95% CI = [.00-.217]) and aggression (B = .02, SE = .02, 95% CI = [.0003-.069])). CONCLUSION: The findings demonstrate an association between diminished resting HRV and psychopathology. Moreover, age-related HRV reductions emerged as a potential psychophysiological mechanism that underlies enhanced vulnerability to distress and aggression following cumulative PTE exposure

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date