Anomalous Dynamics of Forced Translocation

We consider the passage of long polymers of length N through a hole in a membrane. If the process is slow, it is in principle possible to focus on the dynamics of the number of monomers s on one side of the membrane, assuming that the two segments are in equilibrium. The dynamics of s(t) in such a limit would be diffusive, with a mean translocation time scaling as N^2 in the absence of a force, and proportional to N when a force is applied. We demonstrate that the assumption of equilibrium must break down for sufficiently long polymers (more easily when forced), and provide lower bounds for the translocation time by comparison to unimpeded motion of the polymer. These lower bounds exceed the time scales calculated on the basis of equilibrium, and point to anomalous (sub-diffusive) character of translocation dynamics. This is explicitly verified by numerical simulations of the unforced translocation of a self-avoiding polymer. Forced translocation times are shown to strongly depend on the method by which the force is applied. In particular, pulling the polymer by the end leads to much longer times than when a chemical potential difference is applied across the membrane. The bounds in these cases grow as N^2 and N^{1+\nu}, respectively, where \nu is the exponent that relates the scaling of the radius of gyration to N. Our simulations demonstrate that the actual translocation times scale in the same manner as the bounds, although influenced by strong finite size effects which persist even for the longest polymers that we considered (N=512).Comment: 13 pages, RevTeX4, 16 eps figure

Lipid Testing Trends Before and After Hospitalization for Myocardial Infarction Among Adults in the United States, 2008–2019

Background: Routine monitoring of low-density lipoprotein cholesterol (LDL-C) identifies patients who may benefit from modifying lipid-lowering therapies (LLT). However, the extent to which LDL-C testing is occurring in clinical practice is unclear, specifically among patients hospitalized for a myocardial infarction (MI). Methods: Using US commercial claims data, we identified patients with an incident MI hospitalization between 01/01/2008-03/31/2019. LDL-C testing was assessed in the year before admission (pre-MI) and the year after discharge (post-MI). Changes in LDL-C testing were evaluated using a Poisson model fit to pre-MI rates and extrapolated to the post-MI period. We predicted LDL-C testing rates if no MI had occurred (ie, based on pre-MI trends) and estimated rate differences and ratios (contrasting observed vs predicted rates). Results: Overall, 389,367 patients were hospitalized for their first MI during the study period. In the month following discharge, 9% received LDL-C testing, increasing to 27% at 3 months and 52% at 12 months. Mean rates (tests per 1000 patients per month) in the pre-and post-MI periods were 51.9 (95% CI: 51.7, 52.1) and 84.4 (95% CI: 84.1, 84.6), respectively. Over 12 months post-MI, observed rates were higher than predicted rates; the maximum rate difference was 66 tests per 1000 patients in month 2 (rate ratio 2.2), stabilizing at a difference of 15–20 (ratio 1.2–1.3) for months 6–12. Conclusion: Although LDL-C testing increased following MI hospitalization, rates remained lower than recommended by clinical guidelines. This highlights a potential gap in care, where increased LDL-C testing after MI may provide opportunities for LLT modification and decrease risk of subsequent cardiovascular events

Race and delays in breast cancer treatment across the care continuum in the Carolina Breast Cancer Study

Background: After controlling for baseline disease factors, researchers have found that black women have worse breast cancer survival, and this suggests that treatment differences may contribute to poorer outcomes. Delays in initiating and completing treatment are one proposed mechanism. Methods: Phase 3 of the Carolina Breast Cancer Study involved a large, population-based cohort of women with incident breast cancer. For this analysis, we included black women (n = 1328) and white women (n = 1331) with stage I to III disease whose treatment included surgery with or without adjuvant therapies. A novel treatment pathway grouping was used to benchmark the treatment duration (surgery only, surgery plus chemotherapy, surgery plus radiation, or all 3). Models controlled for the treatment pathway, age, and tumor characteristics and for demographic factors related to health care access. Exploratory analyses of the association between delays and cancer recurrence were performed. Results: In fully adjusted analyses, blacks had 1.73 times higher odds of treatment initiation more than 60 days after their diagnosis in comparison with whites (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.04-2.90). Black race was also associated with a longer treatment duration. Blacks were also more likely to be in the highest quartile of treatment duration (OR, 1.69; 95% CI, 1.41-2.02), even after adjustments for demographic and tumor characteristics (OR, 1.31; 95% CI, 1.04-1.64). A nonsignificant trend toward a higher recurrence risk was observed for patients with delayed initiation (hazard ratio, 1.44; 95% CI, 0.89-2.33) or the longest duration (hazard ratio, 1.17; 95% CI, 0.87-1.59). Conclusions: Black women more often had delayed treatment initiation and a longer duration than whites receiving similar treatment. Interventions that target access barriers may be needed to improve timely delivery of care

Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients

Background: Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. Methods: Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. Results: Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. Conclusions: While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control

Internalized HIV Stigma Predicts Suboptimal Retention in Care among People Living with HIV in the United States

HIV-related stigma is a known barrier to retention in care. However, no large-scale, multi-site studies have prospectively evaluated the effect of internalized stigma on retention in care. The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study integrates medical record and survey data from people living with HIV (PLWH) seen in HIV primary care clinics across the United States, and assesses internalized stigma yearly using a validated 4-item Likert scale. We used multivariable logistic regression models to evaluate associations between mean internalized stigma and two prospective retention in care outcomes: keeping the next primary care appointment and keeping all scheduled primary care appointments in the 12 months following stigma assessment. From February 2016 to November 2017, 5968 PLWH completed the stigma assessment and had adequate follow-up time. Mean stigma was 1.9 (standard deviation 1.08). Increased mean stigma scores were associated with decreased odds of attending the next primary care appointment [adjusted odds ratio (aOR) = 0.93, 95% confidence interval (CI) 0.88-0.99, p = 0.02], and all primary care appointments in the subsequent 12 months (aOR = 0.94, 95% CI 0.89-0.99, p = 0.02). In both models, younger age and Black race were also independently associated with suboptimal appointment attendance. There was no support for interactions between internalized stigma and covariates. Internalized HIV stigma had an independent negative effect on the odds of subsequent appointment attendance. This study highlights the importance of identifying even low levels of internalized stigma. Interventions to address internalized HIV stigma are critical to supporting retention in care and improving clinical outcomes

The Human Immunodeficiency Virus (HIV) Index: Using a Patient-Reported Outcome on Engagement in HIV Care to Explain Suboptimal Retention in Care and Virologic Control

Background: We investigated the prospective association between a brief self-report measure of engagement in human immunodeficiency virus (HIV) care (the Index of Engagement in HIV Care; hereafter "Index") and suboptimal retention and viral suppression outcomes. Methods: The Centers for AIDS Research Network of Integrated Clinical Systems cohort study combines medical record data with patient-reported outcomes from 8 HIV clinics in the United States, which from April 2016 to March 2017 included the 10-item Index. Multivariable logistic regression was used to estimate the risk and odds ratios of mean Index scores on 2 outcomes in the subsequent year: (1) not keeping ≥75% of scheduled HIV care appointments; and (2) for those with viral suppression at Index assessment, having viral load >200 copies/mL on ≥1 measurement. We also used generalized linear mixed models (GLMMs) to estimate the risk and odds ratios of appointment nonattendance or unsuppressed viral load at any given observation. We generated receiver operating characteristic curves for the full models overlaid with the Index as a sole predictor. Results: The mean Index score was 4.5 (standard deviation, 0.6). Higher Index scores were associated with lower relative risk of suboptimal retention (n = 2576; logistic regression adjusted risk ratio [aRR], 0.88 [95% confidence interval,. 87-.88]; GLMM aRR, 0.85 [.83-.87]) and lack of sustained viral suppression (n = 2499; logistic regression aRR, 0.75 [.68-.83]; GLMM aRR, 0.74 [.68-.80]). The areas under the receiver operating characteristic curve for the full models were 0.69 (95% confidence interval,. 67-.71) for suboptimal retention and 0.76 (.72-.79) for lack of sustained viral suppression. Conclusions: Index scores are significantly associated with suboptimal retention and viral suppression outcomes

Tensor Correlations Measured in 3He(e,e'pp)n

We have measured the 3He(e,e'pp)n reaction at an incident energy of 4.7 GeV over a wide kinematic range. We identified spectator correlated pp and pn nucleon pairs using kinematic cuts and measured their relative and total momentum distributions. This is the first measurement of the ratio of pp to pn pairs as a function of pair total momentum, $p_{tot}$. For pair relative momenta between 0.3 and 0.5 GeV/c, the ratio is very small at low $p_{tot}$ and rises to approximately 0.5 at large $p_{tot}$. This shows the dominance of tensor over central correlations at this relative momentum.Comment: 4 pages, 4 figures, submitted to PR

Detecting Disengagement from HIV Care before It Is Too Late: Development and Preliminary Validation of a Novel Index of Engagement in HIV Care

Background:Engagement in care is critical to achieving and sustaining optimal benefits of efficacious antiretroviral therapies for HIV infection. Current metrics of engagement in care, including problematic patterns of retention in care, adherence to treatment, and viral suppression, are often detected late in the disengagement process. We sought to develop and validate a patient-centered screener of engagement in care that can be used to identify deficits in patient perceptions of engagement before the development of poor outcomes, including loss to follow-up, treatment nonadherence, virologic failure, and the resulting increased likelihood of HIV-associated morbidity and mortality and onward transmission of HIV.Setting and Methods:Using input from patients, providers, and researchers through in-person focus groups and an online Delphi process, we developed a self-report measure of engagement in care that was validated with 3296 patients from 7 clinics across the United States.Results:Results supported a single dimension of engagement in care measured by 10 items. Lower scores on the HIV Index were related to higher depression and anxiety symptoms, greater use of alcohol and stimulants, and increased likelihood of reporting internalized HIV stigma. Higher Index scores were positively associated with self-report measures of antiretroviral therapy adherence, corroborative clinic records documenting appointment attendance, and increased likelihood of recent viral load suppression.Conclusions:The HIV Index offers promise as a patient-centered diagnostic and prognostic screener for engagement in care that can be used to trigger interventions to promote better clinical outcomes for persons living with HIV

Coherent Photoproduction of pi^+ from 3^He

We have measured the differential cross section for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction. This reaction was studied using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. Real photons produced with the Hall-B bremsstrahlung tagging system in the energy range from 0.50 to 1.55 GeV were incident on a cryogenic liquid $^3$He target. The differential cross sections for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction were measured as a function of photon-beam energy and pion-scattering angle. Theoretical predictions to date cannot explain the large cross sections except at backward angles, showing that additional components must be added to the model.Comment: 11 pages, 16 figure