Regional and racial variations in the utilization of endoscopic retrograde cholangiopancreatography among pancreatic cancer patients in the United States

BackgroundPancreatic cancer is projected to become the second leading cause of cancerâ related deaths by 2030. Endoscopic retrograde cholangiopancreatography (ERCP) is recommended as firstâ line therapy for biliary decompression in pancreatic cancer. The aim of our study was to characterize geographic and racial/ethnic disparities in ERCP utilization among patients with pancreatic cancer.MethodsRetrospective cohort study using the US Surveillance, Epidemiology, and End Results (SEER)â Medicare database to identify patients diagnosed with pancreatic cancer from 2003â 2013. The primary outcome was receipt of ERCP, with or without stent placement, vs any nonâ ERCP biliary intervention.ResultsOf the 36 619 patients with pancreatic cancer, 37.5% (n = 13 719) underwent an ERCP, percutaneous drainage, or surgical biliary bypass. The most common biliary intervention (82.6%) was ERCP. After adjusting for tumor location and stage, Blacks were significantly less likely to receive ERCP than Whites (aOR 0.84, 95% CI 0.72, 0.97) and more likely to receive percutaneous transhepatic biliary drainage (PTBD) (aOR 1.38, 95% CI 1.14, 1.66). Patients in the Southeast and the West were more likely to receive ERCP than those in the Northeast (Southeast aOR 1.21, 95% CI 1.04, 1.40; West aOR 1.16, 95% CI 1.01, 1.32).ConclusionRacial/ethnic and geographic disparities in access to biliary interventions including ERCP exist for patients with pancreatic cancer in the United States. Our results highlight the need for further research and policies to improve access to appropriate biliary intervention for all patients.To date, disparities in the receipt of endoscopic therapies among patients with pancreatic cancer have not been reported. The results from our study suggest that blacks with pancreatic cancer and patients in the Northeast region of the US are less likely to receive the gold standard therapy for obstructive jaundice.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149758/1/cam42225_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149758/2/cam42225.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149758/3/cam42225-sup-0001-Supinfo.pd

The Origin of T Tauri X-ray Emission: New Insights from the Chandra Orion Ultradeep Project

We use the data of the Chandra Orion Ultradeep Project (COUP) to study the nearly 600 X-ray sources that can be reliably identified with optically well characterized T Tauri stars (TTS) in the Orion Nebula Cluster. We detect X-ray emission from more than 97% of the optically visible late-type (spectral types F to M) cluster stars. This proofs that there is no ``X-ray quiet'' population of late-type stars with suppressed magnetic activity. All TTS with known rotation periods lie in the saturated or super-saturated regime of the relation between activity and Rossby numbers seen for main-sequence (MS) stars, but the TTS show a much larger scatter in X-ray activity than seen for the MS stars. Strong near-linear relations between X-ray luminosities, bolometric luminosities and mass are present. We also find that the fractional X-ray luminosity rises slowly with mass over the 0.1 - 2 M_sun range. The plasma temperatures determined from the X-ray spectra of the TTS are much hotter than in MS stars, but seem to follow a general solar-stellar correlation between plasma temperature and activity level. The large scatter about the relations between X-ray activity and stellar parameters seems to be related to the influence of accretion on the X-ray emission. While the X-ray activity of the non-accreting TTS is consistent with that of rapidly rotating MS stars, the accreting stars are less X-ray active (by a factor of ~2-3 on average) and produce much less well defined correlations than the non-accretors. We discuss possible reasons for the suppression of X-ray emission by accretion and the implications of our findings on long-standing questions related to the origin of the X-ray emission from young stars.Comment: accepted for ApJS, COUP Special Issu

Lightning Imaging with LOFAR

We show that LOFAR can be used as a lightning mapping array with a resolution that is orders of magnitude better than existing arrays. In addition the polarization of the radiation can be used to track the direction of the stepping discharges

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Presbyopia:Effectiveness of correction strategies

Presbyopia is a global problem affecting over a billion people worldwide. The prevalence of unmanaged presbyopia is as high as 50% of those over 50 years of age in developing world populations due to a lack of awareness and accessibility to affordable treatment, and is even as high as 34% in developed countries. Definitions of presbyopia are inconsistent and varied, so we propose a redefinition that states “presbyopia occurs when the physiologically normal age-related reduction in the eye's focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual's requirements”. Presbyopia is inevitable if one lives long enough, but intrinsic and extrinsic risk factors including cigarette smoking, pregnancy history, hyperopic or astigmatic refractive error, ultraviolet radiation, female sex (although accommodation is similar to males), hotter climates and some medical conditions such as diabetes can accelerate the onset of presbyopic symptoms. Whilst clinicians can ameliorate the symptoms of presbyopia with near vision spectacle correction, bifocal and progressive spectacle lenses, monovision, translating or multifocal contact lenses, monovision, extended depth of focus, multifocal (refractive, diffractive and asymmetric designs) or ‘accommodating’ intraocular lenses, corneal inlays, scleral expansion, laser refractive surgery (corneal monovision, corneal shrinkage, corneal multifocal profiles and lenticular softening), pharmacologic agents, and electro-stimulation of the ciliary muscle, none fully overcome presbyopia in all patients. While the restoration of natural accommodation or an equivalent remains elusive, guidance is gives on presbyopic correction evaluation techniques

A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis

Type I PKSs often utilise programmed β-branching, via enzymes of an “HMG-CoA synthase (HCS) cassette”, to incorporate various side chains at the second carbon from the terminal carboxylic acid of growing polyketide backbones. We identified a strong sequence motif in Acyl Carrier Proteins (ACPs) where β-branching is known. Substituting ACPs confirmed a correlation of ACP type with β-branching specificity. While these ACPs often occur in tandem, NMR analysis of tandem β-branching ACPs indicated no ACP-ACP synergistic effects and revealed that the conserved sequence motif forms an internal core rather than an exposed patch. Modelling and mutagenesis identified ACP Helix III as a probable anchor point of the ACP-HCS complex whose position is determined by the core. Mutating the core affects ACP functionality while ACP-HCS interface substitutions modulate system specificity. Our method for predicting β-carbon branching expands the potential for engineering novel polyketides and lays a basis for determining specificity rules

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease