Young-Onset Colorectal Cancer: Earlier Diagnoses or Increasing Disease Burden?

Colorectal cancer (CRC) incidence and mortality in the United States have changed strikingly in recent decades. Overall, CRC incidence decreased by >30% from 1975 (59.5 per 100,000) to 2013 (37.9 per 100,000). CRC mortality similarly declined from 28.1 per 100,000 in 1975 to 14.5 per 100,000 in 2013—nearly a 50% decrease.1 Screen-eligible populations, particularly those over age 65, have experienced the largest declines in incidence and mortality

Field theoretic description of charge regulation interaction

In order to find the exact form of the electrostatic interaction between two proteins with dissociable charge groups in aqueous solution, we have studied a model system composed of two macroscopic surfaces with charge dissociation sites immersed in a counterion-only ionic solution. Field-theoretic representation of the grand canonical partition function is derived and evaluated within the mean-field approximation, giving the Poisson-Boltzmann theory with the Ninham-Parsegian boundary condition. Gaussian fluctuations around the mean-field are then analyzed in the lowest order correction that we calculate analytically and exactly, using the path integral representation for the partition function of a harmonic oscillator with time-dependent frequency. The first order (one loop) free energy correction gives the interaction free energy that reduces to the zero-frequency van der Waals form in the appropriate limit but in general gives rise to a mono-polar fluctuation term due to charge fluctuation at the dissociation sites. Our formulation opens up the possibility to investigate the Kirkwood-Shumaker interaction in more general contexts where their original derivation fails.Comment: 12 pages, 9 figures, submitted to EPJ

Autoimmune and viral risk factors are associated with achalasia: A case-control study

Background: Achalasia is a rare esophageal motility disorder of uncertain etiology. While past studies have indicated that autoimmune conditions and viral infections may be associated with development of achalasia, these associations are yet to be examined in large, population-based studies. Methods: A matched case-control study was performed using administrative claim data from the IBM MarketScan Commercial Claims and Encounters Database between 2000 and 2019. A history of selected autoimmune conditions and viral infections was assessed using past medical claims. Multivariable conditional logistic regression was used to account for the matched nature of the study design and further control for confounding by demographic and clinical characteristics when reporting adjusted odds ratios (aORs). Key Results: Among 6769 cases and 27,076 controls, presence of any of the autoimmune conditions studied was associated with increased odds of achalasia (aOR = 1.26, 95% CI: 1.11, 1.42). Scleroderma or systemic sclerosis (aOR = 8.13, 95% CI: 3.34, 19.80) and Addison's disease (aOR = 3.83, 95% CI: 1.83, 8.04) had the strongest associations with achalasia. Presence of any of the viral infections studied was also associated with an increased risk of achalasia (aOR = 1.58, 95% CI: 1.23, 2.01). Varicella zoster virus (aOR = 3.84, 95% CI: 1.94, 7.62) and human papillomavirus (aOR = 1.77, 95% CI: 1.15, 2.73) both had strong relationships with achalasia. Conclusions and Inferences: These findings suggest that achalasia may have autoimmune and viral components contributing to its etiology. Future mechanistic studies could target specific diseases and agents highlighted by this research

Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n=6,862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50-69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50-69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years

RE: Colorectal Cancer Incidence Patterns in the United States, 1974–2013

In the latest issue of the Journal, Siegel et al. report that young adults born around 1990 (and so currently age 20 to 29 years) have double and quadruple the risk of colon and rectal cancer (CRC), respectively, compared with the same age group born in 1950. We believe presenting relative increases in incidence isolated from the absolute risk of CRC in younger adults can be misleading. Using relative or ratio measures to communicate risk of young-onset CRC may lead the casual reader or popular press to misinterpret the extent to which incidence is increasing

On Relativistic Material Reference Systems

This work closes certain gaps in the literature on material reference systems in general relativity. It is shown that perfect fluids are a special case of DeWitt's relativistic elastic media and that the velocity--potential formalism for perfect fluids can be interpreted as describing a perfect fluid coupled to a fleet of clocks. A Hamiltonian analysis of the elastic media with clocks is carried out and the constraints that arise when the system is coupled to gravity are studied. When the Hamiltonian constraint is resolved with respect to the clock momentum, the resulting true Hamiltonian is found to be a functional only of the gravitational variables. The true Hamiltonian is explicitly displayed when the medium is dust, and is shown to depend on the detailed construction of the clocks.Comment: 18 pages, ReVTe

Epidemiologic and Economic Burden of Achalasia in the United States

Background & Aims: Achalasia is a debilitating chronic condition of the esophagus. Currently there are no national estimates on the epidemiologic and economic burden of disease. We sought to estimate trends in incidence and prevalence of achalasia by age-sex strata, and to estimate the total direct medical costs attributed to achalasia in the United States. Methods: We conducted a cohort study using two administrative claims databases: IBM MarketScan Commercial Claims and Encounters database (2001-2018; age <65) and a 20% sample of nationwide Medicare enrollment and claims (2007-2015; age ≥65). Point prevalence was calculated on the first day of each calendar year; the incidence rate captured new cases developed in the ensuing year. Utilization rates of healthcare services and procedures were reported. Mean costs per patient were calculated and standardized to the corresponding U.S. Census Bureau population data to derive achalasia-specific total direct medical costs. Results: The crude prevalence of achalasia per 100,000 persons was 18.0 (95% CI, 17.4, 18.7) in MarketScan and 162.1 (95% CI, 157.6, 166.6) in Medicare. The crude incidence rate per 100,000 person-years was 10.5 (95% CI, 9.9, 11.1) in MarketScan and 26.0 (95% CI, 24.9, 27.2) in Medicare. Incidence and prevalence increased substantially over time in the Medicare cohort, and increased with more advanced age in both cohorts. Utilization of achalasia-specific healthcare was high; national estimates of total direct medical costs exceeded $408 million in 2018. Conclusions: Achalasia has a higher epidemiologic and economic burden in the US than previously suggested, with diagnosis particularly increasing in older patients

Controlling for frailty in pharmacoepidemiologic studies of older adults

Background: Frailty is a geriatric syndrome characterized by weakness and weight loss and is associated with adverse health outcomes. It is often an unmeasured confounder in pharmacoepidemiologic and comparative effectiveness studies using administrative claims data. Methods: Among the Atherosclerosis Risk in Communities (ARIC) Study Visit 5 participants (2011-2013; n = 3,146), we conducted a validation study to compare a Medicare claims-based algorithm of dependency in activities of daily living (or dependency) developed as a proxy for frailty with a reference standard measure of phenotypic frailty. We applied the algorithm to the ARIC participants' claims data to generate a predicted probability of dependency. Using the claims-based algorithm, we estimated the C-statistic for predicting phenotypic frailty. We further categorized participants by their predicted probability of dependency (<5%, 5% to <20%, and ≥20%) and estimated associations with difficulties in physical abilities, falls, and mortality. Results: The claims-based algorithm showed good discrimination of phenotypic frailty (C-statistic = 0.71; 95% confidence interval [CI] = 0.67, 0.74). Participants classified with a high predicted probability of dependency (≥20%) had higher prevalence of falls and difficulty in physical ability, and a greater risk of 1-year all-cause mortality (hazard ratio = 5.7 [95% CI = 2.5, 13]) than participants classified with a low predicted probability (<5%). Sensitivity and specificity varied across predicted probability of dependency thresholds. Conclusions: The Medicare claims-based algorithm showed good discrimination of phenotypic frailty and high predictive ability with adverse health outcomes. This algorithm can be used in future Medicare claims analyses to reduce confounding by frailty and improve study validity

Quantum Cryptography Using Single Particle Entanglement

A quantum cryptography scheme based on entanglement between a single particle state and a vacuum state is proposed. The scheme utilizes linear optics devices to detect the superposition of the vacuum and single particle states. Existence of an eavesdropper can be detected by using a variant of Bell's inequality.Comment: 4 pages, 3figures, revte

Cross-domain interference costs during concurrent verbal and spatial serial memory tasks are asymmetric

Some evidence suggests that memory for serial order is domain-general. Evidence also points to asymmetries in interference between verbal and visual-spatial tasks. We confirm that concurrently remembering verbal and spatial serial lists provokes substantial interference compared with remembering a single list, but we further investigate the impact of this interference throughout the serial position curve, where asymmetries are indeed apparent. A concurrent verbal order memory task affects spatial memory performance throughout the serial positions of the list, but performing a spatial order task affects memory for the verbal serial list only for early list items; in the verbal task only, the final items are unaffected by a concurrent task. Adding suffixes eliminates this asymmetry, resulting in impairment throughout the list for both tasks. These results suggest that domain-general working memory resources may be supplemented with resources specific to the verbal domain, but perhaps not with equivalent spatial resources