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"Fuchs, R"
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Electric vehicle battery chemistry affects supply chain disruption vulnerabilities
We examine the relationship between electric vehicle battery chemistry and supply chain disruption vulnerability for four critical minerals: lithium, cobalt, nickel, and manganese. We compare the nickel manganese cobalt (NMC) and lithium iron phosphate (LFP) cathode chemistries by (1) mapping the supply chains for these four materials, (2) calculating a vulnerability index for each cathode chemistry for various focal countries and (3) using network flow optimization to bound uncertainties. World supply is currently vulnerable to disruptions in China for both chemistries: 80% [71% to 100%] of NMC cathodes and 92% [90% to 93%] of LFP cathodes include minerals that pass through China. NMC has additional risks due to concentrations of nickel, cobalt, and manganese in other countries. The combined vulnerability of multiple supply chain stages is substantially larger than at individual steps alone. Our results suggest that reducing risk requires addressing vulnerabilities across the entire battery supply chain.
Electric vehicle battery supply chains are currently vulnerable to supply disruptions in China, but research shows that the cumulative effect of multiple supply chain steps creates additional vulnerabilities across multiple critical battery minerals.
Journal Article
Land-use change emissions based on high-resolution activity data substantially lower than previously estimated
Land-use and land-cover changes (LULCCs) contributed around one third to the cumulative, anthropogenic CO 2 emissions from 1850 to 2019. Despite its great importance, estimates of the net CO 2 fluxes from LULCC (E LUC ) have high uncertainties, compared to other components of the global carbon cycle. One major source of uncertainty roots in the underlying LULCC forcing data. In this study, we implemented a new high-resolution LULCC dataset (HILDA + ) in a bookkeeping model (BLUE) and compared the results to estimates from simulations based on LUH2, which is the LULCC dataset most commonly used in global carbon cycle models. Compared to LUH2-based estimates, results based on HILDA + show lower total E LUC (global mean difference 1960–2019: 541 TgC yr −1 , 65%) and large spatial and temporal differences in component fluxes (e.g. CO 2 fluxes from deforestation). In general, the congruence of component fluxes is higher in the mid-latitudes compared to tropical and subtropical regions, which is to some degree explained with the different implementations of shifting cultivation in the underlying LULCC datasets. However, little agreement is reached on the trend of the last decade between E LUC estimates based on the two LULCC reconstructions. Globally and in many regions, E LUC estimates based on HILDA + have decreasing trends, whereas estimates based on LUH2 indicate an increase. Furthermore, we analyzed the effect of different resolutions on E LUC estimates. By comparing estimates from simulations at 0.01 ∘ and 0.25 ∘ resolution, we find that component fluxes of estimates based on the coarser resolution tend to be larger compared to estimates based on the finer resolution, both in terms of sources and sinks (global mean difference 1960–2019: 36 TgC yr −1 , 96%). The reason for these differences are successive transitions: these are not adequately represented at coarser resolution, which has the effect that—despite capturing the same extent of transition areas—overall less area remains pristine at the coarser resolution compared to the finer resolution.
Journal Article
Patient desire for spiritual assessment is unmet in urban and rural primary care settings
Background
Incorporation of patient religious and spiritual beliefs in medical care has been shown to improve the efficacy of medical interventions and health outcomes. While previous study has highlighted differences in patient desire for spiritual assessment based on patient religiosity, little is known about patient desire for spiritual assessment based on community type, particularly in urban compared to rural communities. We hypothesized that, given demographic trends which show a higher degree of religiosity in rural areas, patients in rural communities will be more likely to desire spiritual assessment.
Methods
In this cross-sectional study of 141 adult primary care patients in rural and urban Colorado at non-religiously affiliated clinics, we surveyed patient demographic information, measures of religiosity, patient desire for spiritual assessment, and frequency of spiritual assessment in practice. Univariate logistic regression analyses were used to compare the two populations.
Results
In both Denver County (urban) and Lincoln County (rural) over 90% of patients identified as religious, spiritual, or a combination of the two. Thirty eight percent (38.3%) of patients in Denver County and 49.1% of patients in Lincoln desired spiritual assessment. Over 97% of patients in both areas reported rarely or never being asked about their R/S within the past year. For patients who have had five or more clinic visits in the past year, more than 91% in both areas stated they have never or rarely been asked about their beliefs.
Conclusions
While the majority of patients in this study identify as religious or spiritual and many patients desire spiritual assessment, the majority of patients have never or rarely been asked about their spirituality within the past year. This demonstrates a significant gap between patient preference and provider practice of spiritual assessment in the primary care setting, which was similar in both rural and urban settings. This highlights the need for interdisciplinary focus on spiritual assessment and incorporation of patient R/S beliefs in medical care to provide holistic patient care and improve health outcomes.
Journal Article
Science and research policy at the end of Moore’s law
The integrated circuit is today synonymous with the concept of technological progress. In the seven decades since the invention of the transistor at Bell Labs, relentless progress in the development of semiconductor devices — Moore’s law — has been achieved despite regular warnings from industry observers about impending limits. Here, drawing on technical and organizational archival work and oral histories, we argue that the current technological and structural challenges facing the industry are unprecedented and undermine the incentives for continued collective action in research and development, which has underpinned the past 50 years of transformational worldwide economic growth and social advance. We conclude by arguing that the lack of private incentives, due in part to a splintering of technology trajectories and short-term private profitability of many of these new splinters, creates a case for greatly increased public funding and the need for leadership beyond traditional stakeholders.
This Perspective argues that the challenges facing the semiconductor industry are unprecedented and undermine incentives for continued collective action in research and development, potentially threatening world-wide economic growth; significantly increased public funding, as well as leadership beyond traditional stakeholders, is required.
Journal Article
A New Class of Multimerization Selective Inhibitors of HIV-1 Integrase
The quinoline-based allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are promising candidates for clinically useful antiviral agents. Studies using these compounds have highlighted the role of IN in both early and late stages of virus replication. However, dissecting the exact mechanism of action of the quinoline-based ALLINIs has been complicated by the multifunctional nature of these inhibitors because they both inhibit IN binding with its cofactor LEDGF/p75 and promote aberrant IN multimerization with similar potencies in vitro. Here we report design of small molecules that allowed us to probe the role of HIV-1 IN multimerization independently from IN-LEDGF/p75 interactions in infected cells. We altered the rigid quinoline moiety in ALLINIs and designed pyridine-based molecules with a rotatable single bond to allow these compounds to bridge between interacting IN subunits optimally and promote oligomerization. The most potent pyridine-based inhibitor, KF116, potently (EC50 of 0.024 µM) blocked HIV-1 replication by inducing aberrant IN multimerization in virus particles, whereas it was not effective when added to target cells. Furthermore, KF116 inhibited the HIV-1 IN variant with the A128T substitution, which confers resistance to the majority of quinoline-based ALLINIs. A genome-wide HIV-1 integration site analysis demonstrated that addition of KF116 to target or producer cells did not affect LEDGF/p75-dependent HIV-1 integration in host chromosomes, indicating that this compound is not detectably inhibiting IN-LEDGF/p75 binding. These findings delineate the significance of correctly ordered IN structure for HIV-1 particle morphogenesis and demonstrate feasibility of exploiting IN multimerization as a therapeutic target. Furthermore, pyridine-based compounds present a novel class of multimerization selective IN inhibitors as investigational probes for HIV-1 molecular biology.
Journal Article
Major Trends in the U.S. Health Economy since 1950
As the United States struggles to emerge from an economic crisis, policymakers and the public have homed in on skyrocketing health care expenditures. What lessons can be drawn from the evolution, since 1950, in sources of payment and objects of expenditures in health care?
Rapid advances in medical science and technology, substantial gains in health outcomes attributable to medical care, and budget-busting increases in health care expenditures fueled by private and public insurance have marked the past six decades of health care in the United States. As the country struggles to emerge from a multiyear financial and economic crisis, policymakers and the public have increasingly homed in on those skyrocketing health care expenditures. What lessons can be drawn from the evolution, since 1950, in the sources of payment and objects of expenditures in the health care arena?
Health Expenditures
The rapid growth of health . . .
Journal Article
Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation
Integration is essential for HIV-1 replication, and the viral integrase (IN) protein is an important therapeutic target. Allosteric IN inhibitors (ALLINIs) that engage the IN dimer interface at the binding site for the host protein lens epithelium-derived growth factor (LEDGF)/transcriptional coactivator p75 are an emerging class of small molecule antagonists. Consistent with the inhibition of a multivalent drug target, ALLINIs display steep antiviral dose–response curves ex vivo. ALLINIs multimerize IN protein and concordantly block its assembly with viral DNA in vitro, indicating that the disruption of two integration-associated functions, IN catalysis and the IN-LEDGF/p75 interaction, determines the multimode mechanism of ALLINI action. We now demonstrate that ALLINI potency is unexpectedly accounted for during the late phase of HIV-1 replication. The compounds promote virion IN multimerization and, reminiscent of class II IN mutations, block the formation of the electron-dense viral core and inhibit reverse transcription and integration in subsequently infected target cells. Mature virions are recalcitrant to ALLINI treatment, and compound potency during virus production is independent of the level of LEDGF/p75 expression. We conclude that cooperative multimerization of IN by ALLINIs together with the inability for LEDGF/p75 to effectively engage the virus during its egress from cells underscores the multimodal mechanism of ALLINI action. Our results highlight the versatile nature of allosteric inhibitors to primarily inhibit viral replication at a step that is distinct from the catalytic requirement for the target enzyme. The vulnerability of IN to small molecules during the late phase of HIV-1 replication unveils a pharmacological Achilles’ heel for exploitation in clinical ALLINI development.
Journal Article
Geographic and Racial Variation in Premature Mortality in the U.S.: Analyzing the Disparities
Life expectancy at birth, estimated from United States period life tables, has been shown to vary systematically and widely by region and race. We use the same tables to estimate the probability of survival from birth to age 70 (S(70)), a measure of mortality more sensitive to disparities and more reliably calculated for small populations, to describe the variation and identify its sources in greater detail to assess the patterns of this variation. Examination of the unadjusted probability of S(70) for each US county with a sufficient population of whites and blacks reveals large geographic differences for each race-sex group. For example, white males born in the ten percent healthiest counties have a 77 percent probability of survival to age 70, but only a 61 percent chance if born in the ten percent least healthy counties. Similar geographical disparities face white women and blacks of each sex. Moreover, within each county, large differences in S(70) prevail between blacks and whites, on average 17 percentage points for men and 12 percentage points for women. In linear regressions for each race-sex group, nearly all of the geographic variation is accounted for by a common set of 22 socio-economic and environmental variables, selected for previously suspected impact on mortality; R(2) ranges from 0.86 for white males to 0.72 for black females. Analysis of black-white survival chances within each county reveals that the same variables account for most of the race gap in S(70) as well. When actual white male values for each explanatory variable are substituted for black in the black male prediction equation to assess the role explanatory variables play in the black-white survival difference, residual black-white differences at the county level shrink markedly to a mean of -2.4% (+/-2.4); for women the mean difference is -3.7% (+/-2.3).
Journal Article