Operating Principles of Peristaltic Pumping through a Dense Array of Valves

Immersed nonlinear elements are prevalent in biological systems that require a preferential flow direction. A certain class of models is investigated where the fluid is driven by peristaltic pumping and the nonlinear elements are ideal valves that completely suppress backflow. This highly nonlinear system produces discontinuous solutions that are difficult to study. As the density of valves increases, the pressure and flow are well-approximated by a continuum of valves which can be analytically treated. Interestingly, two different pumping mechanisms emerge from this model. At low frequencies, diffusive transport pushes open all but one valve, and the radius takes the shape of the imposed force. At high frequencies, half of the valves open, and the flow is determined by the advective transport induced by peristalsis. In either case, the induced flow is linear in the amplitude of the peristaltic forces and is independent of pumping direction. Despite the continuum approximation used, the physical valve density is accounted for by modifying the resistance of the fluid appropriately. The suppression of backflow causes a net benefit in adding valves when the valve density is low, but once the density is high enough, the dominant valve effect is to suppress the forward flow, suggesting there is an optimum number of valves per wavelength.Comment: 11 pages, 7 figure

From localized to well-mixed: How commuter interactions shape disease spread

Interactions between commuting individuals can lead to large-scale spreading of rumors, ideas, or disease, even though the commuters have no net displacement. The emergent dynamics depend crucially on the commuting distribution of a population, that is how the probability to travel to a destination decays with distance from home. Applying this idea to epidemics, we will demonstrate the qualitatively different infection dynamics emerging from populations with different commuting distributions. If the commuting distribution is exponentially localized, we recover a reaction-diffusion system and observe Fisher waves traveling at a speed proportional to the characteristic commuting distance. If the commuting distribution has a long tail, then no finite-velocity waves can form, but we show that, in some regimes, there is nontrivial spatial dependence that the well-mixed approximation neglects. We discuss how, in all cases, an initial dispersal-dominated regime can allow the disease to go undetected for a finite amount of time before exponential growth takes over. This "offset time" is a quantity of huge importance for epidemic surveillance and yet largely ignored in the literature.Comment: 26 pages, 15 figures; made minor edits for clarit

The Impact of Market Structure on Oncology Care

The market structure of oncology care is undergoing dramatic consolidation. Little work has examined how market structure impacts oncology care. This study has three objectives: (1) investigate the effect of market structure on geographic access to care for patients receiving infused chemotherapy; (2) investigate the impact of market structure on Medicare reimbursement for patients receiving infused chemotherapy; and (3) evaluate how the market structure impacts the speed of diffusion in the use of new high- and low-value treatments for patients. Using a 20% sample of Medicare Fee-For-Service claims from 2008 to 2014, we identified a cohort of 142,770 patients receiving infused chemotherapy for cancer and 89,096 new users of chemotherapy. We assessed relationships between 1) competition and the number of chemotherapy-administering physicians within 25, 50, and 75 miles of the patient’s zip code and the distance traveled to receive chemotherapy, 2) competition and Medicare expenditures for infused chemotherapy, and 3) competition and diffusion of new treatments. We find that a one standard deviation increase in logged Herfindahl-Hirschman Index (HHI) (i.e., market becoming less competitive) increases the average distance traveled from 100 to 112 miles and decreases the average number of physicians within 75 miles from 346 to 312 physicians. When examining spending, we find that spending decreases as markets become less competitive at the claim service-line level and the day level but is not impacted when looking at total spending in the six months following treatment initiation. Finally, we examined five newly approved medications or existing medications with new indications: (nab-paclitaxel, bendamustine, degarelix, temsiroliimus, and bevacizumab) and find that the impact of competition on the diffusion of a new treatment varies by treatment. Nab-paclitaxel, a lower value drug, diffuses slower as markets become less competitive, whereas bendamustine, a higher value drug, diffuses faster as markets become less competitive. We do not find significant associations between market competition and drug diffusion for the other drugs studied. Competition impacts patients’ geographic access to care. The association between competition and healthcare spending and diffusion of medications is not consistent. Future research should examine how competition impacts patients’ access to care in other clinical areas, drivers for increased spending in consolidated areas, and the quality of care is impacted by competition for cancer patients.Doctor of Philosoph

Factors Associated With Tyrosine Kinase Inhibitor Initiation and Adherence Among Medicare Beneficiaries With Chronic Myeloid Leukemia

There is substantial concern surrounding affordability of orally administered anticancer therapies, particularly for Medicare beneficiaries. We examined rates of initiation and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid leukemia (CML) with and without cost-sharing subsidies. We selected TKIs given their effectiveness and strong indication for use among patients diagnosed with CML

Cost-Utility Analysis of Cancer Prevention, Treatment, and Control

Substantial innovation related to cancer prevention and treatment has occurred in recent decades. However, these innovations have often come at a significant cost. Cost-utility analysis provides a useful framework to assess if the benefits from innovation are worth the additional cost. This systematic review on published cost-utility analyses related to cancer care is from 1988 through 2013. Analyses were conducted in 2013–2015

Probing the Interiors of Very Hot Jupiters Using Transit Light Curves

Accurately understanding the interior structure of extra-solar planets is critical for inferring their formation and evolution. The internal density distribution of a planet has a direct effect on the star-planet orbit through the gravitational quadrupole field created by the rotational and tidal bulges. These quadrupoles induce apsidal precession that is proportional to the planetary Love number ($k_{2p}$, twice the apsidal motion constant), a bulk physical characteristic of the planet that depends on the internal density distribution, including the presence or absence of a massive solid core. We find that the quadrupole of the planetary tidal bulge is the dominant source of apsidal precession for very hot Jupiters ($a \lesssim 0.025$ AU), exceeding the effects of general relativity and the stellar quadrupole by more than an order of magnitude. For the shortest-period planets, the planetary interior induces precession of a few degrees per year. By investigating the full photometric signal of apsidal precession, we find that changes in transit shapes are much more important than transit timing variations. With its long baseline of ultra-precise photometry, the space-based \emph{Kepler} mission can realistically detect apsidal precession with the accuracy necessary to infer the presence or absence of a massive core in very hot Jupiters with orbital eccentricities as low as $e \simeq 0.003$. The signal due to $k_{2p}$ creates unique transit light curve variations that are generally not degenerate with other parameters or phenomena. We discuss the plausibility of measuring $k_{2p}$ in an effort to directly constrain the interior properties of extra-solar planets.Comment: updated, improved, and expanded manuscript has been accepted by the Astrophysical Journal; 19 pages, 7 figure

Socioeconomic Inequalities in Statin Adherence Under Universal Coverage: Does Sex Matter?

BACKGROUND: Previous research shows that low socioeconomic position (SEP; especially low income) is associated with statin nonadherence. We investigated the relationship between SEP and statin adherence in a country with universal coverage using group-based trajectory modeling in addition to the proportion of days covered. METHODS AND RESULTS: Using data from Finnish healthcare registers, we identified 116 846 individuals, aged 45 to 75 years, who initiated statin therapy for primary prevention of cardiovascular disease. We measured adherence as proportion of days covered over an 18-month period since initiation and identified different adherence patterns based on monthly adherence with group-based trajectory modeling. When adjusted for age, marital status, residential area, clinical characteristics, and copayment, low SEP was associated with statin nonadherence (proportion of days covered <80%) among men (eg, lowest versus highest income quintile: odds ratio, 1.41; 95% confidence interval, 1.32-1.50; basic versus higher-degree education: odds ratio, 1.18; 95% confidence interval, 1.13-1.24; unemployment versus employment: odds ratio, 1.17; 95% confidence interval, 1.10-1.25). Among women, the corresponding associations were different (P<0.001 for sex-by-income quintile, sex-by-education level, and sex-by-labor market status interactions) and mainly nonsignificant. Results based on adherence trajectories showed that men in low SEP were likely to belong to trajectories presenting a fast decline in adherence. CONCLUSIONS: Low SEP was associated with overall and rapidly increasing statin nonadherence among men. Conversely, in women, associations between SEP and nonadherence were weak and inconsistent. Group-based trajectory modeling provided insight into the dynamics of statin adherence and its association with SEP

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Importance National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population. Objective To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment. Design, Setting, and Participants This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020. Exposures Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims. Main Outcomes and Measures Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics. Results Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001). Conclusions and Relevance These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy

Endocrine Therapy Initiation among Older Women with Ductal Carcinoma In Situ

Background. Although treatment of ductal carcinoma in situ (DCIS) is controversial, national guidelines recommend considering endocrine therapy for women with estrogen receptor- (ER-) positive DCIS or those undergoing breast conserving surgery (BCS) without radiation. We evaluated uptake and predictors of endocrine therapy use among older women with DCIS. Methods. In the SEER-Medicare database, we identified women aged 65+ years diagnosed with DCIS during 2007–2011. We evaluated demographic, tumor, and treatment characteristics associated with endocrine therapy initiation. Results. Among 2,945 women with DCIS, 41% initiated endocrine therapy (66% tamoxifen, 34% aromatase inhibitors). Initiation was more common among women with ER-positive than ER-negative DCIS (48% versus 16%; HR = 3.75, 95% CI: 2.91–4.83); 28% of women with unknown ER status initiated endocrine therapy. Initiation was less common after BCS alone compared to BCS with radiation (32% versus 50%; HR = 0.69, 95% CI: 0.59–0.80). Conclusions. Less than half of older women with DCIS initiate endocrine therapy to prevent second breast cancers. Our findings suggest use was more common, but not exclusive, among women with ER-positive DCIS, but not among women who underwent BCS alone. Endocrine therapy should be targeted toward patients most likely to benefit from its use