Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells

<p>Abstract</p> <p>Background</p> <p>Ephrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of EFNA1 and potential differences in the manner in which they interact with EPHA2.</p> <p>Results</p> <p>Using a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface, away from cell-cell contacts, and promoted the growth of HeLa cells.</p> <p>Conclusions</p> <p>We conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation.</p

Association between Post-Hospital Clinic and Telephone Follow-up Provider Visits with 30-Day Readmission Risk in an Integrated Health System

BACKGROUND: Follow-up visits with clinic providers after hospital discharge may not be feasible for some patients due to functional limitations, transportation challenges, need for physical distancing, or fear of exposure especially during the current COVID-19 pandemic. METHODS: The aim of the study was to determine the effects of post-hospital clinic (POSH) and telephone (TPOSH) follow-up provider visits versus no visit on 30-day readmission. We used a retrospective cohort design based on data from 1/1/2017 to 12/31/2019 on adult patients (n = 213,513) discharged home from 15 Kaiser Permanente Southern California hospitals. Completion of POSH or TPOSH provider visits within 7 days of discharge was the exposure and all-cause 30-day inpatient and observation stay readmission was the primary outcome. We used matching weights to balance the groups and Fine-Gray subdistribution hazard model to assess for readmission risk. RESULTS: Unweighted all-cause 30-day readmission rate was highest for patients who completed a TPOSH (17.3%) followed by no visit (14.2%), non-POSH (evaluation and management visits that were not focused on the hospitalization: 13.6%) and POSH (12.6%) visits. The matching weighted models showed that the effects of POSH and TPOSH visits varied across patient subgroups. For high risk (LACE 11+) medicine patients, both POSH (HR: 0.77, 95% CI: 0.71, 0.85, P \u3c .001) and TPOSH (HR: 0.91, 95% CI: 0.83, 0.99, P = .03) were associated with 23 and 9% lower risk of 30-day readmission, respectively, compared to no visit. For medium to low risk medicine patients (LACE\u3c 11) and all surgical patients regardless of LACE score or age, there were no significant associations for either visit type with risk of 30-day readmission. CONCLUSIONS: Post-hospital telephone follow-up provider visits had only modest effects on 30-day readmission in high-risk medicine patients compared to clinic visits. It remains to be determined if greater use and comfort with virtual visits by providers and patients as a result of the pandemic might improve the effectiveness of these encounters

Inequity in access to transplantation in the UK

Background and objectives Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. Design, setting, participants, & measurements In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. Results Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%–33% for preemptive listing and 25%–40% for listing after starting dialysis. Patient factors, including increasing age, most comorbidities, body mass index >35 kg/m2, and lower socioeconomic status, were associated with a lower likelihood of being listed and accounted for 89% and 97% of measured intercenter variation for preemptive listing and listing within 2 years of starting dialysis, respectively. Asian (odds ratio, 0.49; 95% confidence interval, 0.33 to 0.72) and Black (odds ratio, 0.43; 95% confidence interval, 0.26 to 0.71) participants were both associated with reduced access to preemptive listing; however Asian participants were associated with a higher likelihood of being listed after starting dialysis (odds ratio, 1.42; 95% confidence interval, 1.12 to 1.79). As for center factors, being registered at a transplanting center (odds ratio, 3.1; 95% confidence interval, 2.36 to 4.07) and a universal approach to discussing transplantation (odds ratio, 1.4; 95% confidence interval, 1.08 to 1.78) were associated with higher preemptive listing, whereas using a written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). Conclusions Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system

Working with the homeless: The case of a non-profit organisation in Shanghai

This article addresses a two-pronged objective, namely to bring to the fore a much neglected social issue of homelessness, and to explore the dynamics of state-society relations in contemporary China, through a case study of a non-profit organisation (NPO) working with the homeless in Shanghai. It shows that the largely invisible homelessness in Chinese cities was substantially due to exclusionary institutions, such as the combined household registration and 'detention and deportation' systems. Official policy has become much more supportive since 2003 when the latter was replaced with government-run shelters, but we argue that the NPO case demonstrates the potential for enhanced longer-term support and enabling active citizenship for homeless people. By analysing the ways in which the NPO offers services through collaboration and partnership with the public (and private) actors, we also argue that the transformations in postreform China and the changes within the state and civil society have significantly blurred their boundaries, rendering state-society relations much more complex, dynamic, fluid and mutually embedded

Seasonal Migration Distance Varies With Natal Dispersal and Predicts Parasitic Infection in Song Sparrows

Seasonal migration and natal dispersal represent the major large-scale movements in the lives of animals. Individuals that are relatively prone to movement and exploration might thus be more likely to disperse and also to migrate farther. Such movement might be either negatively associated with parasitic infection (if infection prevents hosts from successful long-distance migration) or positively associated (e.g. if longer-distance migrants encounter more abundant or more diverse parasites). We examined whether natal dispersal tendency predicts seasonal migration distance in song sparrows (Melospiza melodia) and whether migration distance predicts infection with bloodborne parasites upon arrival at the breeding grounds. Migration distance, inferred from stable hydrogen isotope analysis (δ2H) of winter-grown tissue, was repeatable (repeatability = 0.41) over years. Birds that were more likely to have immigrated from outside the breeding grounds, as inferred from genetic assignment tests, also overwintered farther south, as inferred from stable isotope analysis. The finding that individuals more prone to movement in the context of natal dispersal also tended to travel farther, on average, in the context of seasonal migration suggests consistent individual variation in large-scale movements across these two contexts. Although statistically significant, this effect was modest in scope and subtle relative to sex differences in inferred migration distance. Among after-second-year individuals, but not yearlings, longer-distance migrants were more likely, on average, to be infected with bloodborne parasites. Individual variation in propensity to long-distance movement may interact with age-related variation in exposure or susceptibility to parasites, to shape the role of animal migration in transporting infectious disease

Evaluating Native American Bird Use and Bird Assemblage Variability along the Oregon Coast

Native American use of birds on the Oregon coast is not well known and has never been synthesized to present a regional understanding. We rectify this by analyzing data from 26 zooarchaeological assemblages, including three previously unpublished bird assemblages: Umpqua/Eden (35DO83), Whale Cove (35LNC60), and the Dunes Site (35CLT27). We employ a series of non-parametric randomization tests to directly evaluate patterns of taxonomic diversity, correlations with nearby breeding colonies, and broader procurement strategies discussed in ethnohistorical accounts. We compare the assemblages to contemporary surveys of naturally beached birds as observed by COASST (Coastal Observation Seabird Survey Team) and evaluate whether archaeological specimens were scavenged from the beach. While 71% of the identified bird remains belong to just three families (Anatidae, Alcidae, and Procellariidae), closer analysis reveals the incredible diversity of birds used by Oregon coast Native Americans. The assemblages vary considerably in terms of taxonomic diversity and composition, leading us to conclude that people used birds opportunistically, likely incorporating multiple strategies, including hunting, collecting beached carcasses and targeting cormorant colonies. We hope that the methods and approaches employed here will inspire other archaeologists to devote more attention to bird assemblages, and how their study can inform conservation efforts

The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in non-dialysis chronic kidney disease : a systematic review

Objective: People with nondialysis-dependent chronic kidney disease (CKD) and renal transplant recipients (RTRs) have compromised physical function and reduced physical activity (PA) levels. Whilst established in healthy older adults and other chronic diseases, this association remains underexplored in CKD. We aimed to review the existing research investigating poor physical function and PA with clinical outcome in nondialysis CKD. Data sources: Electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials) were searched until December 2017 for cohort studies reporting objective or subjective measures of PA and physical function and the associations with adverse clinical outcomes and all-cause mortality in patients with nondialysis CKD stages 1–5 and RTRs. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42016039060). Review methods: Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare and Research Quality (AHRQ) standards. Results: A total of 29 studies were included; 12 reporting on physical function and 17 on PA. Only eight studies were conducted with RTRs. The majority were classified as ‘good’ according to the AHRQ standards. Although not appropriate for meta-analysis due to variance in the outcome measures reported, a coherent pattern was seen with higher mortality rates or prevalence of adverse clinical events associated with lower PA and physical function levels, irrespective of the measurement tool used. Sources of bias included incomplete description of participant flow through the study and over reliance on self-report measures. Conclusions: In nondialysis CKD, survival rates correlate with greater PA and physical function levels. Further trials are required to investigate causality and the effectiveness of physical function and PA interventions in improving outcomes. Future work should identify standard assessment protocols for PA and physical function

Use of electronic medical records (EMR) for oncology outcomes research: assessing the comparability of EMR information to patient registry and health claims data

Electronic medical records (EMRs) are used increasingly for research in clinical oncology, epidemiology, and comparative effectiveness research (CER)

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease

Whose Research Is This? - Participatory Secondary Data Analysis with People Living with Dementia

Drawing on our approach and findings from a secondary interrogation of an existing qualitative dataset, this work set out to challenge assumptions of practice through using participatory methods. Our approach brought two key aspects together: applying the theories of Douglas’s Cultural Theory of Risk and Tronto’s Ethic of Care, and a collaboration with people living with dementia as co-analysts in the co-production (interpretation) of knowledge and representing the experiences within the qualitative dataset. The research generated an understanding of relational care and the subtle ways in which relationships change for someone with dementia. In this case, we describe the processes we followed and reflect on the demands and challenges, experienced as researchers, in focusing on reflexivity, multiple voicing, literary styling, and performance. In our description of how we had to relinquish any sense of a concluding authoritative voice, we highlight the innovation in this participatory secondary data analysis and encourage others to engage with this dialogue