Background
Although recommended lung cancer screening with low‐dose computed tomography scanning (LDCT) reduces mortality among high‐risk adults, annual screening rates remain low. This study ...complements a previous nationwide assessment of access to lung cancer screening within 40 miles by evaluating differences in accessibility across rural and urban settings for the population aged 50 to 80 years and a subset eligible population based on the 2021 US Preventive Services Task Force LDCT lung screening recommendations.
Methods
Distances from population centers to screening facilities (American College of Radiology Lung Cancer Screening Registry) were calculated, and the number of individuals who had access within graduating distances, including 10, 20, 40, 50, and 100 miles, were estimated. Census tract results were aggregated to counties, and both geographies were classified with rural‐urban schemas.
Results
Approximately 5% of the eligible population did not have access to lung cancer screening facilities within 40 miles; however, different patterns of accessibility were observed at different distances, between regions, and across rural‐urban environments. Across all distances and geographies, there was a larger percentage of the population in rural geographies with no access. Although the rural population represented approximately 8% of the eligible population, the larger percentage of the rural population with no access was noteworthy and translated into a larger number of individuals with no access at longer distance thresholds (≥40 miles).
Conclusions
Disparities in access should be examined as both percentages of the population and numbers of individuals with no access in order to tailor interventions to communities and increase access. Geospatial analysis at the census tract level is recommended to help to identify optimal focus areas and reach the most people.
Lay Summary
As annual lung cancer screening rates remain low, this study examines access to lung cancer screening nationwide and across rural and urban settings.
A geographic information system network analysis of census tract–level populations is used to estimate access at different distances, including 10, 20, 40, 50, and 100 miles, and the results are aggregated to counties.
Approximately 5% of the eligible population does not have access to screening facilities within 40 miles; however, different patterns of accessibility are observed at different distances, between regions, and across rural‐urban environments.
Across all distances and geographies, there is a larger percentage of the population in rural geographies with no access.
This study uses geospatial analysis to examine access to lung cancer screening at graduating distances nationwide and across rural‐urban settings. Approximately 5% of the eligible population does not have access to lung cancer screening facilities within 40 miles; however, different patterns of accessibility are observed at different distances, between regions, and across rural‐urban environments.
Screening current and former heavy smokers 55 to 80 years of age for lung cancer (LC) with low-dose chest CT scanning has been recommended by the United States Preventive Services Task Force since ...2013. Although the number of screening facilities in the United States has increased, screening uptake has been slow.
To what extent is geographic access to screening facilities a barrier for screening uptake nationally?
Screening facilities were defined as American College of Radiology (ACR) Lung Cancer Screening Registry (LCSR) facilities. Analysis was performed at different geographic levels using a road network to calculate travel distances for the recommended age groups. Full access to screening was defined as the entire 55- to 79-year-old population being within 40 miles of an ACR LCSR facility. No access was defined as lack of access by the entire target population. Partial access was expressed in intervening quartiles. A geospatial approach then was used to integrate accessibility with smoking prevalence and LC mortality rates to identify potential focus areas visually.
Screening facilities addresses were geocoded to identify 3,592 unique locations. Analysis of census tracts and aggregation to counties revealed that among 3,142 counties, adults 55 to 79 years of age have full access to an LC screening registry facility in 1,988 (63%) counties, partial access in 587 (19%) counties, and no access in 567 (18%) counties. Overall, less than 6% of those 55 to 79 years of age do not have access to registry screening facilities. Variation in screening facility access was noted across the United States, between states, and within some states.
It is recommended to calculate accessibility using subcounty geographies and to examine variation regionally and within states. A foundation geographic accessibility layer can be integrated with other variables to identify geographic disparities in access to screening and to focus on areas for interventions. Identifying areas of greatest need can inform state and local officials and healthcare organizations when planning and implementing LC screening programs.
Our previous studies have found that activation of Wnt/β-catenin signaling resulted in mouse prostatic intraepithelial neoplasia (mPIN). In the large probasin promoter directed SV40-large T-antigen ...(LPB-Tag) expressing mouse prostate, mPIN forms with rare areas of adenocarcinoma. Combining expression of both Wnt-signaling and Tag expression in the mouse prostate, we have studied the role of Wnt/β-catenin signaling in the progression from mPIN to adenocarcinoma. Our results show that the prostates of mice expressing Tag alone or nuclear β-catenin alone developed mPIN, whereas the activation of both Tag and the Wnt/β-catenin pathway resulted in invasive prostate adenocarcinoma. Furthermore, Foxa2, a forkhead transcription factor, was induced by active Wnt/β-catenin signaling, and the expression of Foxa2 was associated with the invasive phenotype in the primary prostate cancer. In the LPB-Tag/dominant active (DA) β-catenin prostates, MMP7, a Wnt/β-catenin target gene, was upregulated. Furthermore, we also assessed AR and AR signaling pathway in these LPB-Tag/DA β-catenin mice. Although β-catenin is a well-known AR co-activator in vitro, our study provides strong in vivo evidences indicating that both AR protein and the AR pathway were downregulated in the prostate of LPB-Tag/DA β-catenin mice. Histological analysis shows that prostate sections derived from the LPB-Tag/DA β-catenin mice display neuroendocrine differentiation (NED), but NE cancer does not develop. Together, our findings indicate that Wnt/β-catenin signaling has an important role in the progression of mPIN to prostate adenocarcinoma.
Chromatin proteins mediate replication, regulate expression, and ensure integrity of the genome. So far, a comprehensive inventory of interphase chromatin has not been determined. This is largely due ...to its heterogeneous and dynamic composition, which makes conclusive biochemical purification difficult, if not impossible. As a fuzzy organelle, it defies classical organellar proteomics and cannot be described by a single and ultimate list of protein components. Instead, we propose a new approach that provides a quantitative assessment of a protein's probability to function in chromatin. We integrate chromatin composition over a range of different biochemical and biological conditions. This resulted in interphase chromatin probabilities for 7635 human proteins, including 1840 previously uncharacterized proteins. We demonstrate the power of our large‐scale data‐driven annotation during the analysis of cyclin‐dependent kinase (CDK) regulation in chromatin. Quantitative protein ontologies may provide a general alternative to list‐based investigations of organelles and complement Gene Ontology.
Synopsis
A probabilistic definition of interphase chromatin captures its dynamic and regulated composition with a new proteomics‐based quantitative protein ontology approach. This resource is subsequently applied for the identification of novel factors whose interphase chromatin association depends on cyclin‐dependent kinase (CDK).
Static protein lists in organellar proteomics are replaced by degrees of chromatin involvement.
Chromatin components are defined by biological co‐behavior instead of biochemical co‐purification.
Interphase chromatin probabilities (ICPs) for 7635 proteins focus datasets on likely chromatin factors.
Chromatin enrichment for proteomics (ChEP) defines a simple but efficient procedure to enrich chromatin for proteomic analysis.
Proteomic analysis of CDK‐dependent chromatin composition reveals novel cell cycle‐regulated chromatin factors.
A combination of biochemical and biological classifiers results in assignment of a protein ‘interphase chromatin probability’ (ICP), making an organelle whose dynamic composition defies rigorous black‐and‐white delineation amenable to quantitative proteomics.
The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate carcinogenesis. In this study, we show that in human prostate tumors, coexpression of c-MYC and PIM1 is associated ...with higher Gleason grades. Using a tissue recombination model coupled with lentiviral-mediated gene transfer we find that Pim1 is weakly oncogenic in naive adult mouse prostatic epithelium. However, it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks. Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity. c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62) phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant had higher rates of proliferation than grafts expressing wild type c-MYC but did not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c-MYC in vivo involves additional mechanisms other than enhancement of c-MYC activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas show evidence of neuroendocrine (NE) differentiation. Additional studies, including the identification of tumor cells coexpressing androgen receptor and NE cell markers synaptophysin and Ascl1 suggested that NE tumors arose from adenocarcinoma cells through transdifferentiation. These results directly show functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer.
Appropriate interaction between pantograph and catenary is imperative for smooth operation of electric trains. Changing heights of overhead lines to accommodate level crossings, overbridges, and ...tunnels pose significant challenges in maintaining consistent current collection performance as the pantograph aerodynamic profile, and thus aerodynamic load changes significantly with operational height. This research aims to analyse the global flow characteristics and aerodynamic forces acting on individual components of an HSX pantograph operating in different configurations and orientations, such that the results can be combined with multibody simulations to obtain accurate dynamic insight into contact forces. Specifically, computational fluid dynamics simulations are used to investigate the pantograph component loads in a representative setting, such as that of the recessed cavity on a Class 800 train. From an aerodynamic perspective, this study indicates that the total drag force acting on non-fixed components of the pantograph is larger for the knuckle-leading orientation rather than the knuckle-trailing, although the difference between the two is found to reduce with increasing pantograph extension. Combining the aerodynamic loads acting on individual components with multibody tools allows for realistic dynamic insight into the pantograph behaviour. The results obtained show how considering aerodynamic forces enhance the realism of the models, leading to behaviour of the pantograph–catenary contact forces closely matching that seen in experimental tests.
The sensation of nausea is one of the most debilitating human experiences. Current antiemetic therapies are effective in reducing vomiting, but are less effective in reducing acute and delayed nausea ...and are completely ineffective in reducing anticipatory nausea. Recent preclinical evidence using a selective rat model of nausea (conditioned gaping reactions) has revealed that cannabinoids have great promise as treatments for nausea and that their antinausea effects may be mediated by the interoceptive insular cortex.
The SCOPE trials (SCOPE 1, NeoSCOPE and SCOPE 2) have been the backbone of oesophageal RT trials in the UK. Many changes in oesophageal RT techniques have taken place in this time. The SCOPE trials ...have, in addition to adopting these new techniques, been influential in aiding centres with their implementation. We discuss the progress made through the SCOPE trials and include details of a questionnaire sent to participating centres. to establish the role that trial participation played in RT changes in their centre.
Questionnaires were sent to 47 centres, 27 were returned.
100% of centres stated their departmental protocol for TVD was based on the relevant SCOPE trial protocol. 4DCT use has increased from 42 to 71%. Type B planning algorithms, mandated in the NeoSCOPE trial, were used in 79.9% pre NeoSCOPE and now in 83.3%. 12.5% of centres were using a stomach filling protocol pre NeoSCOPE, now risen to 50%. CBCT was mandated for IGRT in the NeoSCOPE trial. 66.7% used this routinely pre NeoSCOPE/SCOPE 2 which has risen to 87.5% in the survey.
The results of the questionnaires show how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care.
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