The Value Proposition for Pathologists: A Population Health Approach

© The Author(s) 2020. The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of populations and improve health-care outcomes for both individual patients and populations. For the profession to thrive, pathologists will need to focus on extending their roles outside the laboratory beyond the traditional role in the analytic phase of testing. This should include leadership in ensuring correct ordering and interpretation of laboratory testing and leadership in population health programs. Pathologists in training will need to learn key concepts in informatics and data analytics, health-care economics, public health, implementation science, and health systems science. While these changes may reduce reimbursement for the traditional activities of pathologists, new opportunities arise for value creation and new compensation models. This report reviews these opportunities for pathologist leadership in utilization management, precision medicine, reducing diagnostic errors, and improving health-care outcomes

Perfluoroalkyl chemicals and elevated serum uric acid in US adults

Anoop Shankar, Jie Xiao, Alan DucatmanDepartment of Community Medicine, West Virginia University School of Medicine, Morgantown, WV, USABackground: Perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, are man-made chemicals that have been detected in the blood of over 98% of the US population. Serum uric acid is a novel biomarker, even mild elevations of which has been implicated in the development of hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. We examined the relationship of serum perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, and elevated uric acid levels in a representative sample of US adults.Methods: We examined 3883 participants from the 1999–2000 and 2003–2006 National Health and Nutritional Examination Surveys,a representative, multiethnic population-based survey of noninstitutionalized US adults. Serum perfluorooctanoic acid and perfluorooctane sulfonate were analyzed as quartiles. The main outcome was hyperuricemia.Results: We found that serum levels of perfluoroalkyl chemicals, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with hyperuricemia. This association appeared to be independent of confounders such as age, gender, race-ethnicity, body mass index, diabetes, hypertension, and serum cholesterol. Compared with subjects in quartile 1 (referent), the multivariate odds ratio for hyperuricemia among subjects in quartile 4 was 1.97 (95% confidence interval 1.44–2.70, P < 0.0001) for perfluorooctanoic acid and 1.48% (95% confidence interval 0.99–2.22, P = 0.0433) for perfluorooctane sulfonate. This observed association persisted in subgroup analysis by gender and body mass index.Conclusion: Our results demonstrate that elevated levels of perfluoroalkyl chemicals are associated with hyperuricemia even at low perfluoroalkyl chemical exposure levels as seen in the US general population.Keywords: perfluoroalkyl chemicals, perfluorooctanoic acid, perfluorooctane sulfonate, uric aci

Association between Six Environmental Chemicals and Lung Cancer Incidence in the United States

Background. An increased risk of lung cancer has been observed at exposure to certain industrial chemicals in occupational settings; however, less is known about their carcinogenic potential to the general population when those agents are released into the environment. Methods. We used the Toxics Release Inventory (TRI) database and Surveillance, Epidemiology, and End Results (SEER) data to conduct an ecological study at the county level. We used multiple linear regression to assess the association of age-adjusted lung cancer incidence with the quantities of on-site air and water releases of six selected industrial chemicals including arsenic, 1,3 butadiene, cadmium, chromium, formaldehyde, and nickel after controlling for other risk variables. Results. Overall, we observed a significantly increased risk of lung cancer incidence associated with releases of chromium, formaldehyde, and nickel. The links were present for both males and females. Significant effects were present in nonmetropolitan but not metropolitan counties. Releases of arsenic, 1,3 butadiene, and cadmium were reported by small numbers of facilities, and no relationships to lung cancer incidence were detected. Conclusions. Our results suggest that environmental exposure to chromium, formaldehyde, and nickel from TRI sites may increase population risk of lung cancer. These findings need to be confirmed in individual-level studies, but in congruence with the precautionary principle in environmental science, support prudent efforts to limit release of these agents into the environment

Local Magnetism in Strongly Correlated Electron Systems with Orbital Degrees of Freedom

University of Minnesota Ph.D. dissertation. July 2017. Major: Physics. Advisor: Natalia Perkins. 1 computer file (PDF); ix, 103 pages.The central aim of my research is to explain the connection between the macroscopic behavior and the microscopic physics of strongly correlated electron systems with orbital degrees of freedom through the use of effective models. My dissertation focuses on the sub-class of these materials where electrons appear to be localized by interactions, and magnetic ions have well measured magnetic moments. This suggests that we can capture the low-energy physics of the material by employing a minimal model featuring localized spins which interact with each other through exchange couplings. I describe Fe$_{1+y}$Te and $\beta$-Li$_2$IrO$_3$ with effective models primarily focusing on the spins of the magnetic ions, in this case Fe and Ir, respectively. The goal with both materials is to gain insight and make predictions for experimentalists. In chapter 2, I focus on Fe$_{1+y}$Te. I describe why we believe the magnetic ground state of this material, with an observed Bragg peak at $\mathbf{Q}=(\pm \frac{\pi}{2}, \frac{\pi}{2})$, can be described by a Heisenberg model with 1st, 2nd, and 3rd neighbor interactions. I present two possible ground states of this model in the small $J_1$ limit, the bicollinear and plaquette states. In order to predict which ground state the model prefers, I calculate the spin wave spectrum with $1/S$ corrections, and I find the model naturally selects the ``plaquette state." I give a brief description of the ways this result could be tested using experimental techniques such as polarized neutron scattering. In chapter 3, I extend the model used in chapter 2. This is necessary because the Heisenberg model we employed cannot explain why Fe$_{1+y}$Te undergoes a phase transition as $y$ is increased. We add an additional elements to our calculation; we assume that electrons in some of the Fe 3D orbitals have selectively localized while others remain itinerant. We write a new Hamiltonian, where localized moments acquire a new long-range RKKY-like interaction from interactions with the itinerant electrons. We are able to reproduce the phase diagram found from experimentalists, and make predictions about how Fe$_{1+y}$Te could potentially be driven into a ``stripe" magnetic ground state. In chapter 4, I examine another strongly correlated material, $\beta$-Li$_2$IrO$_3$, which exhibits Kitaev physics. I begin with a minimal model employing nearest neighbor isotropic and anisotropic exchange couplings between neighboring Iridium ions. I calculate the phase diagram, and find two states. I characterize both states in terms of spins along the zigzag chains of the hyperhoneycomb lattice, and calculate linear spin waves for both states. I find that, besides for special points in our phase diagram, the excitations are gapped. As the spectrum has many branches, I calculate the dynamic structure factor to find which branches of the spin wave spectrum have the highest intensity. It will be interesting to compare my dynamic structure factor results to single crystal inelastic neutron scattering, which to this point has not been performed for $\beta$-Li$_2$IrO$_3$

Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro

BACKGROUND: Gleevec (aka STI571, Imatinib) is a recently FDA approved anti-tumor drug for chronic myelogenous leukemia. Gleevec binds specifically to BCR-ABL tyrosine kinase and inhibit the tyrosine kinase activity. It cross-reacts with another two important membrane tyrosine kinase receptors, c-kit and PDGF receptors. We sought to investigate if Gleevec has a potential role in treatment of non-small cell lung cancer. RESULTS: We have shown that Gleevec alone can inhibit the A549 lung cancer cell growth in dose-dependent manner, and the optimal concentration of Gleevec inhibition of A549 cell growth is at the range of 2–3 μM (IC50). We have also shown that A549 cells are resistant to cisplatin treatment (IC50 64 μM). Addition of Gleevec to the A549 cells treated with cisplatin resulted in a synergistic cell killing effect, suggesting that Gleevec can potentiate the effect of cisplatin on A549 cells. We also showed that the A549 lung cancer cells expresses the platelet derived growth factor receptor α, and the inhibitory effects of Gleevec on A549 cells is likely mediated through inhibition of PDGFR α phosphorylation. We further tested 33 lung cancer patients' tumor specimens to see the frequency of PDGFR-α expression by tissue micro-arrays and immunohistochemistry. We found that 16 of the 18 squamous carcinomas (89%), 11 of the 11 adenocarcinomas (100%), and 4 of the 4 small cell lung cancers (100%) expressed PDGFR-α. CONCLUSION: These results suggest a potential role of Gleevec as adjuvant therapeutic agent for treatment of non-small cell lung cancer

Magnetic structure and excitation spectrum of the hyperhoneycomb Kitaev magnet β-Li2IrO3

© 2018 American Physical Society. We present a theoretical study of the static and dynamical properties of the three-dimensional, hyperhoneycomb Kitaev magnet β-Li2IrO3. We argue that the observed incommensurate order can be understood in terms of a long-wavelength twisting of a nearby commensurate period-3 state, with the same key qualitatively features. The period-3 state shows very different structure when either the Kitaev interaction K or the off-diagonal exchange anisotropy Γ is dominant. A comparison of the associated static spin structure factors with reported scattering experiments in zero and finite fields gives strong evidence that β-Li2IrO3 lies in the regime of dominant Kitaev coupling, and that the Heisenberg exchange J is much weaker than both K and Γ. Our predictions for the magnon excitation spectra, the dynamical spin structure factors, and their polarization dependence provide additional distinctive fingerprints that can be checked experimentally

Tetryl Exposure: Forgotten Hazards Of Antique Munitions

Background: Older yet still abundant munitions such as tetryl present easily forgotten health hazards and associated needs for worker protection. Case presentation: Symptoms and findings from 22 workers who were exposed to tetryl are summarized. Conclusions: This study highlights the health hazards from exposure to tetryl. Occupational health professionals need to maintain vigilance to protect workers from the risks of handling older munitions

Perfluoroalkyl substance excretion: Effects of organic anion-inhibiting and resin-binding drugs in a community setting.

BACKGROUND: Longer serum half-lives of perfluoroalkyl substances (PFAS) in humans compared to other species has been attributed to differences in the activity of organic anion transporters (OAT). METHODS: Among 56,175 adult participants in the community-based C8 Health Project, 23 subjects were taking the uricosuric OAT-inhibitor probenecid, and 36 subjects were taking the bile acid sequestrant cholestyramine. In regression models of log transformed serum PFAS, medication effects were estimated in terms of mean ratios, adjusting for age, gender, BMI, estimated glomerular filtration rate (eGFR) and water-district of residence. RESULTS: Probenecid was associated with modest, but not statistically significant increases in serum PFAS concentrations. In contrast, cholestyramine significantly lowered serum PFAS concentrations, notably for perfluorooctane sulfonic acid (PFOS). CONCLUSIONS: The effectiveness of cholestyramine in a community setting supports the importance of gastrointestinal physiology for PFAS excretion kinetics, especially for PFOS. We did not find clear evidence that probenecid, an inhibitor of OAT, affects PFAS clearance