Racial and ethnic disparities in cervical cancer screening from three U.S. healthcare settings

INTRODUCTION: This study sought to characterize racial and ethnic disparities in cervical cancer screening and follow-up of abnormal findings across 3 U.S. healthcare settings. METHODS: Data were from 2016 to 2019 and were analyzed in 2022, reflecting sites within the Multi-level Optimization of the Cervical Cancer Screening Process in Diverse Settings & Populations Research Center, part of the Population-based Research to Optimize the Screening Process consortium, including a safety-net system in the southwestern U.S., a northwestern mixed-model system, and a northeastern integrated healthcare system. Screening uptake was evaluated among average-risk patients (i.e., no previous abnormalities) by race and ethnicity as captured in the electronic health record, using chi-square tests. Among patients with abnormal findings requiring follow-up, the proportion receiving colposcopy or biopsy within 6 months was reported. Multivariable regression was conducted to assess how clinical, socioeconomic, and structural characteristics mediate observed differences. RESULTS: Among 188,415 eligible patients, 62.8% received cervical cancer screening during the 3-year study period. Screening use was lower among non-Hispanic Black patients (53.2%) and higher among Hispanic (65.4%,) and Asian/Pacific Islander (66.5%) than among non-Hispanic White patients (63.5%, all p\u3c0.001). Most differences were explained by the distribution of patients across sites and differences in insurance. Hispanic patients remained more likely to screen after controlling for a variety of clinical and sociodemographic factors (risk ratio=1.14, CI=1.12, 1.16). Among those receiving any screening test, Black and Hispanic patients were more likely to receive Pap-only testing (versus receiving co-testing). Follow-up from abnormal results was low for all groups (72.5%) but highest among Hispanic participants (78.8%, p\u3c0.001). CONCLUSIONS: In a large cohort receiving care across 3 diverse healthcare settings, cervical cancer screening and follow-up were below 80% coverage targets. Lower screening for Black patients was attenuated by controlling for insurance and site of care, underscoring the role of systemic inequity. In addition, it is crucial to improve follow-up after abnormalities are identified, which was low for all populations

Carbon dynamics of the Weddell Gyre, Southern Ocean

The accumulation of carbon within the Weddell Gyre and its exchanges across the gyre boundaries are investigated with three recent full-depth oceanographic sections enclosing this climatically important region. The combination of carbonmeasurements with ocean circulation transport estimates from a box inverse analysis reveals that deepwater transports associated with Warm Deep Water (WDW) and Weddell Sea Deep Water dominate the gyre’s carbon budget, while a dual-cell vertical overturning circulation leads to both upwelling and the delivery of large quantities of carbon to the deep ocean. Historical sea surface pCO2 observations, interpolated using a neural network technique, confirm the net summertime sink of 0.044 to 0.058 ± 0.010 Pg C / yr derived from the inversion. However, a wintertime outgassing signal similar in size results in a statistically insignificant annual air-to-sea CO2 flux of 0.002± 0.007 Pg C / yr (mean 1998–2011) to 0.012 ± 0.024 Pg C/ yr (mean 2008–2010) to be diagnosed for the Weddell Gyre. A surface layer carbon balance, independently derived fromin situ biogeochemical measurements, reveals that freshwater inputs and biological drawdown decrease surface ocean inorganic carbon levels more than they are increased by WDW entrainment, resulting in an estimated annual carbon sink of 0.033 ± 0.021 Pg C / yr. Although relatively less efficient for carbon uptake than the global oceans, the summertime Weddell Gyre suppresses the winter outgassing signal, while its biological pump and deepwater formation act as key conduits for transporting natural and anthropogenic carbon to the deep ocean where they can reside for long time scales

The rehabilitation enhancing aging through connected health (REACH) study: study protocol for a quasi-experimental clinical trial

Background: Mobility limitations among older adults increase the risk for disability and healthcare utilization. Rehabilitative care is identified as the most efficacious treatment for maintaining physical function. However, there is insufficient evidence identifying a healthcare model that targets prevention of mobility decline among older adults. The objective of this study is to evaluate the preliminary effectiveness of a physical therapy program, augmented with mobile tele-health technology, on mobility function and healthcare utilization among older adults. Methods: This is a quasi-experimental 12-month clinical trial conducted within a metropolitan-based healthcare system in the northeastern United States. It is in parallel with an existing longitudinal cohort study evaluating mobility decline among community-dwelling older adult primary care patients over one year. Seventy-five older adults (≥ 65–95 years) are being recruited using identical inclusion/exclusion criteria to the cohort study. Three aims will be evaluated: the effect of our program on 1) physical function, 2) healthcare utilization, and 3) healthcare costs. Changes in patient-reported function over 1 year in those receiving the intervention (aim 1) will be compared to propensity score matched controls (N = 150) from the cohort study. For aims 2 and 3, propensity scores, derived from logistic regression model that includes demographic and diagnostic information available through claims and enrollment information, will be used to match treatment and control patients in a ratio of 1:2 or 1:3 from a Medicare Claims Registry derived from the same geographic region. The intervention consists of a one-year physical therapy program that is divided between a combination of outpatient and home visits (6–10 total visits) and is augmented on a computerized tablet using of a commercially available application to deliver a progressive home-based exercise program emphasizing lower-extremity function and a walking program. Discussion Incorporating mobile health into current healthcare models of rehabilitative care has the potential to decrease hospital visits and provide a longer duration of care. If the hypotheses are supported and demonstrate improved mobility and reduced healthcare utilization, this innovative care model would be applicable for optimizing the maintenance of functional independence among community-dwelling older adults. Trial registration ClinicalTrial.gov Identifier: NCT02580409 (Date of registration October 14, 2015)

An Observationally Constrained Evaluation of the Oxidative Capacity in the Tropical Western Pacific Troposphere

Hydroxyl radical (OH) is the main daytime oxidant in the troposphere and determines the atmospheric lifetimes of many compounds. We use aircraft measurements of O3, H2O, NO, and other species from the Convective Transport of Active Species in the Tropics (CONTRAST) field campaign, which occurred in the tropical western Pacific (TWP) during January–February 2014, to constrain a photochemical box model and estimate concentrations of OH throughout the troposphere. We find that tropospheric column OH (OHCOL) inferred from CONTRAST observations is 12 to 40% higher than found in chemical transport models (CTMs), including CAM-chem-SD run with 2014 meteorology as well as eight models that participated in POLMIP (2008 meteorology). Part of this discrepancy is due to a clear-sky sampling bias that affects CONTRAST observations; accounting for this bias and also for a small difference in chemical mechanism results in our empirically based value of OHCOL being 0 to 20% larger than found within global models. While these global models simulate observed O3 reasonably well, they underestimate NOx (NO + NO2) by a factor of two, resulting in OHCOL ~30% lower than box model simulations constrained by observed NO. Underestimations by CTMs of observed CH3CHO throughout the troposphere and of HCHO in the upper troposphere further contribute to differences between our constrained estimates of OH and those calculated by CTMs. Finally, our calculations do not support the prior suggestion of the existence of a tropospheric OH minimum in the TWP, because during January–February 2014 observed levels of O3 and NO were considerably larger than previously reported values in the TWP

Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells

Introduction Resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies is an emerging clinical problem. The efficacy of anti-EGFR therapies can be influenced by the presence of heregulins (HRGs), which can bind erbB3/4 receptors and can activate alternative signalling pathways. In the present study we have examined whether HRG signalling can circumvent EGFR blockade in an EGFR-positive tamoxifen-resistant MCF-7 (Tam-R) breast cancer cell line. Methods Tam-R cells, incubated with the selective EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839), were exposed to HRGβ1 and the effects on erbB receptor dimerization profiles and on activation of associated downstream signalling components were assessed by immunoprecipitation, western blotting and immunocytochemistry. The effects of HRGβ1 on gefitinib-treated Tam-R cell growth and invasion were also examined, and HRGβ1 expression levels were assessed in breast cancer tissue by immunohistochemistry to address the potential clinical relevance of such a resistance mechanism. Results In Tam-R cells, HRGβ1 promoted erbB3/erbB2 and erbB3/EGFR heterodimerization, promoted ERK1/2 and AKT pathway activation and increased cell proliferation and invasion. Gefitinib prevented HRGβ1-driven erbB3/EGFR heterodimerization, ERK1/2 activation and Tam-R cell proliferation, but HRGβ1-driven erbB3/erbB2 heterodimerization, AKT activation and Tam-R cell invasion were maintained. A combination of gefitinib and the phosphatidylinositol 3-kinase inhibitor LY294002 effectively blocked HRGβ1-mediated intracellular signalling activity, growth and invasion in Tam-R cells. Similarly, targeting erbB2 with trastuzumab in combination with gefitinib in Tam-R cells reduced HRGβ1-induced erbB2 and ERK1/2 activity; however, HRGβ1-driven AKT activity and cell growth were maintained while cell invasion was significantly enhanced with this combination. In clinical tissue all samples demonstrated cytoplasmic tumour epithelial HRGβ1 protein staining, with expression correlating with EGFR positivity and activation of both AKT and ERK1/2. Conclusion HRGβ1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. This may have implications for the effectiveness of anti-EGFR therapies in breast cancer as HRGβ1 is enriched in many EGFR-positive breast tumours

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.

Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed a pharmacogenomic analysis of MEKi-sensitive versus MEKi-resistant colorectal cancer cell lines. Strikingly, interferon- and inflammatory-related gene sets were enriched in cell lines exhibiting intrinsic and acquired resistance to MEK inhibition. The bromodomain inhibitor JQ1 suppressed interferon-stimulated gene (ISG) expression and in combination with MEK inhibitors displayed synergistic effects and induced apoptosis in MEKi-resistant colorectal cancer cell lines. ISG expression was confirmed in patient-derived organoid models, which displayed resistance to trametinib and were resensitized by JQ1 co-treatment. In in vivo models of colorectal cancer, combination treatment significantly suppressed tumor growth. Our findings provide a novel explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, known for its inflammatory nature. Moreover, the high expression of ISGs was associated with significantly reduced survival of colorectal cancer patients. Excitingly, we have identified novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer

Variation in eligibility criteria from studies of radiculopathy due to a herniated disc and of neurogenic claudication due to lumbar spinal stenosis: a structured literature review

STUDY DESIGN: A structured literature review. SUMMARY OF THE BACKGROUND DATA: Widely recognized classification criteria for rheumatologic disorders have resulted in well-defined patient populations for clinical investigation. OBJECTIVE: We sought to determine whether similar criteria were needed for back pain disorders by examining variability in eligibility criteria in published studies. METHODS: Studies involving radiculopathy due to lumbar herniated disc (HD) and for neurogenic claudication due to lumbar spinal stenosis (LSS) were identified. Randomized controlled trials published between January 1, 2006 and October 1, 2008 in select peer reviewed journals were retrieved, their eligibility criteria were identified and categorized. RESULTS: Twelve eligible HD studies were identified. Thirteen unique categories of eligibility criteria were identified with a mean of 3.9 (+/-2.0) and a range from 0 to 8 categories per study. More categories were present for studies that included nonsurgical (5.6 +/- 2.5) treatment for studies with only surgical treatment (2.6 +/- 1.7) P = 0.04). Seven LSS studies met eligibility criteria, and 9 unique categories were identified. A mean of 5.0 (+/-2.2) categories with a range from 2 to 7 was used per study. CONCLUSION: Wide variation in the number and type of eligibility criteria from randomized clinical trials of well defined back pain syndromes was identified. These results support the need for developing and disseminating international classification criteria for these clinical conditions

Understanding the response of tropical cyclone structure to the assimilation of synthetic wind profiles

AbstractThis study examines how varying wind profile coverages in the tropical cyclone (TC) core, near-environment and broader synoptic environment affect the structure and evolution of a simulated Atlantic hurricane through data assimilation. Three sets of observing system simulation experiments (OSSEs) are examined in this paper. The first experiment establishes a benchmark for the case study specific to the forecast system used by assimilating idealized profiles throughout the parent domain. The second presents how TC analyses and forecasts respond to varying the coverage of swaths produced by polar-orbiting satellites of idealized wind profiles. The final experiment assesses the role of TC inner-core observations by systematically removing them radially from the center. All observations are simulated from a high-resolution regional “Nature Run” of a hurricane and the tropical atmosphere, assimilated an Ensemble Square-Root Kalman Filter and the Hurricane Weather and Research Forecast (HWRF) regional model. Results compare observation impact to the analyses, domain-wide and TC centric error statistics, and TC structural differences among the experiments. The study concludes that the most accurate TC representation is a result of the assimilation of collocated and uniform thermodynamic and kinematics observations. Intensity forecasts are improved with increased inner core wind observations, even if the observations are only available once daily. Domain-wide root-mean-square errors are significantly reduced when the TC is observed during a period of structural change, like rapid intensification. The experiments suggest the importance of wind observations and the role of inner-core surveillance when analyzing and forecasting realistic TC structure