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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Recent years have witnessed the rise of a range of authoritarian populist, illiberal, far-right, nativist, and extremist parties. We have seen democratic structures threatened or incrementally dismantled through the subversion of an established democratic party by an outsider or ascendance of the extremist wing of a right-wing party. Parties and party leaders occupying an ill-defined space on the political spectrum today generally present a much greater threat to democratic governance than overtly antidemocratic fringe outfits. The ambiguity of such parties, their growing size, their entry into government, the subversion of “good” democratic parties by a “bad” leadership, and the rise of the “shadow party” mean that contemporary political party threats seriously frustrate the possibility of remedial action afforded by existing public law and policy mechanisms. They also require us to reflect anew on crafting novel remedies and to revisit our assumptions about parties as creatures of central constitutional importance.
Galba truncatula is one of the most distributed intermediate hosts of Fasciola hepatica across Europe, North Africa and South America. Therefore, understanding the environmental preferences of this species is vital for developing control strategies for fascioliasis and other trematodes such as Calicophoron daubneyi. This systematic literature review evaluates the current understanding of the snail's environmental preferences to identify factors which might aid control and areas where further research is needed. Searches were conducted using Google Scholar and PubMed and included papers published up to August 2023. After filtration, 198 papers with data from 64 countries were evaluated, and data regarding habitat type and habitat pH were noted, along with any other information pertaining to the snail's environmental preferences. The results show that G. truncatula can survive in a diverse range of climates and habitats, generally favours shallow slow-moving water or moist bare mud surfaces, temperatures between 10 and 25°C and was found in habitats with a water pH ranging from 5.0 to 9.4. However, there is limited understanding of the impact of several factors, such as the true optimum pH and temperature preferences within the respective tolerance limits or the reason for the snail's apparent aversion to peatland. Further research is needed to clarify the impact of biotic and abiotic factors on the snail to create robust risk assessments of fluke infection and assess opportunities for environmental control strategies, and for predicting how the snail and fluke transmission may be impacted by climate change.
Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.
Aims
To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.
Method
We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.
Results
Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.
Conclusions
We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.
Control of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa spread in healthcare settings begins with timely and accurate laboratory testing practices. Survey results show most Veterans Affairs facilities are performing recommended tests to identify these organisms. Most facilities report sufficient resources to perform testing, though medium-complexity facilities report some perceived barriers.
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA) are drug-resistant pathogens causing high mortality rates with limited treatment options. Understanding the incidence of these organisms and laboratory knowledge of testing protocols is important for controlling their spread in healthcare settings. This project assessed how often Veterans Affairs (VA) healthcare facilities identify CRAB and CRPA and testing practices used. Method: An electronic survey was distributed to 126 VA acute care facilities September-October 2023. The survey focused on CRAB and CRPA incidence, testing and identification, and availability of testing resources. Responses were analyzed by complexity of patients treated at VA facilities (High, Medium, Low) using Fisher’s exact tests. Result: 77 (61.1%) facilities responded, most in urban settings (85.4%). Most respondents were lead or supervisory laboratory technologists (84.2%) from high complexity facilities (69.0%). Few facilities detected CRAB ≥ once/month (4.4%), with most reporting that they have not seen CRAB at their facility (55.0%). CRPA was detected more frequently: 19% of facilities with isolates ≥ once/month, 29.2% a few times per year, and 26.9% reporting had not seen the organism. No differences in CRAB or CRPA incidence was found by facility complexity. Nearly all facilities, regardless of complexity, utilize the recommended methods of MIC or disk diffusion to identify CRAB or CRPA (91.9%) with remaining facilities reporting that testing is done off-site (7.8%). More high complexity facilities perform on-site testing compared to low complexity facilities (32.0% vs 2.7%, p=0.04). 83% of laboratories test for Carbapenemase production, with one-fourth using off-site reference labs. One-fourth of facilities perform additional antibiotic susceptibility testing for CRAB and CRPA isolates, most of which test for susceptibility to combination antibiotics; no differences between complexities were found. Agreement that sufficient laboratory and equipment resources were available was higher in high complexity than in medium complexity facilities (70.7% vs 33.3%, p=0.01), but not low complexity facilities (43.8%). Conclusion: Having timely and accurate testing protocols for CRAB and CRPA are important to quickly control spread and reduce associated mortality. This study shows that most VA protocols follow recommended testing and identification guidelines. Interestingly, there was no difference in CRAB or CRPA incidence for facilities providing higher vs lower complexity of care. While high and low complexity facilities generally reported sufficient resources for CRAB and CRPA evaluation, some medium-complexity labs, who may feel more compelled than low-complexity labs to bring testing in house, reported that additional resources would be required.
Background: CAP is often inappropriately treated with agents active against multidrug-resistant organisms (MDRO; methicillin-resistant S. aureus [MRSA] and P. aeruginosa [PSA]) and for prolonged duration. We assessed the relationship between antibiotic use with ATS/IDSA guideline-unjustified empiric and definitive MDRO therapy and prolonged duration in non-ICU inpatients with CAP at 105 VA Medical Centers. Methods: From VA Corporate Data Warehouse data, we identified patients with discharge ICD-10-CM codes consistent with CAP from 1/2022-3/2023, excluding cases with 14 days of antibiotic therapy, ICU admission, concurrent infections, or severe immunocompromise. We considered as jultified empiric (≤third day of hospitalization) therapy: anti-MRSA therapy for patients with prior positive MRSA cultures, anti-PSA therapy for patients with prior positive PSA cultures, and both anti-MRSA & anti-PSA therapy in patients with severe pneumonia and intravenous antibiotics in the prior 3 months. Definitive (>third day of hospitalization) anti-MDRO therapy was considered unjustified in patients who had achieved clinical stability and whose cultures did not grow MRSA or PSA. Prolonged duration (>6 days of therapy) was unjustified if patients were clinically stable or discharged by day 5. Results: The median age of the 29,260 patients was 75 (IQR 69,81); 4.6% were women. While 33% and 22% of patients received empiric or definitive MDRO therapy, such therapy was jultified in 12% and 0.5%, respectively. Median facility use of empiric and definitive MDRO therapy was 31% (IQR 25%,38%) and 20% (15%,23%), respectively (Figure 1); this use was unjustified in 89% (85%,93%) and 100% (100%,100%), respectively. Pearson’s correlation coefficient between MDRO therapy and rates of unjustified empiric and definitive MDRO therapy for CAP was 0.54 and 0.61, respectively (Figure 2). Although 99% of patients were discharged or stable by day 5, 42% received prolonged therapy. The median frequency of prolonged therapy was 39% (33%,48%); facility rates of prolonged therapy had a correlation of 0.56 with total antibiotic use and 0.46 with MDRO therapy (Figure 3). Discussion: Based on electronic documentation, we identified 1) substantial opportunities to reduce unjustified anti-MDRO therapy and the duration of therapy in hospitalized non-ICU patients with CAP; 2) a moderate correlation of unjustified anti-MDRO therapy with increased MDRO antibiotic use and of prolonged duration of therapy with increased total and MDRO antibiotic use. The correlation of lower quality prescribing with increased antibiotic use provides further impetus for tools such as dashboards (Figure 4) to assist antibiotic stewards in designing and monitoring interventions to reduce unjustified therapy.
This study explores the transformative effects of the Community Plunge, an educational program at the Wake Forest University School of Medicine (WFUSOM), on healthcare delivery, community engagement, and trainee perspectives. It addresses the broader context of health outcomes, where clinical care only accounts for 20%, emphasizing the critical role of social determinants of health (SDOH) and individual behaviors in the remaining 80%.
Methods:
WFUSOM’s Community Plunge, established in 2002, involves a guided tour of the community, discussions with residents, and debriefing sessions. Qualitative interviews with 20 clinicians were conducted to extract key themes and insights.
Results:
The study identified several key outcomes. First, participants gained crucial insights into the community’s history, structural challenges, and prevalent SDOH, enhancing their understanding of the diverse patient populations they serve. Second, the program positively influenced clinician attitudes, fostering empathy, reducing paternalism, and promoting holistic patient care. Third, participants expressed a desire for increased community involvement and reported career trajectory changes toward advocacy and volunteerism. However, challenges such as time constraints were acknowledged.
Conclusions:
The study advocates for collaborative efforts to enhance the program’s impact, including proactive measures to ensure respectful engagement during community tours. It positions the Community Plunge as an innovative, scalable, and transformative strategy for experiential SDOH exposure, crucial for the evolving social consciousness of healthcare learners.
Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.
Methods:
An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as “VA Bug Alert” (VABA). Use through 8/2023 was assessed.
Results:
VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber.
Conclusions:
A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
Methods
As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
Results
Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
Conclusions
Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
We consider a model in which the correlation between shocks to consumption and to expected future consumption growth is nonzero and varies over time. We validate this assumption empirically using the model’s implication that time variation in consumption growth persistence (CGP) drives the correlation between stock and bond returns. Our model implies that the stock–bond correlation is also related to the predictive relation between bond yields and future stock returns. Finally, we provide suggestive evidence that asset price fluctuations are the primary driver of changes in CGP.
We develop and analyse a continuum model of two-phase slurry dynamics for planetary cores. Mixed solid–liquid slurry regions may be ubiquitous in the upper cores of small terrestrial bodies and have also been invoked to explain anomalous seismic structure in the F-layer at the base of Earth's liquid iron core. These layers are expected to influence the dynamics and evolution of planetary cores, including their capacity to generate global magnetic fields; however, to date, models of two-phase regions in planetary cores have largely ignored the complex fluid dynamics that arises from interactions between phases. As an initial application of our model, and to focus on fundamental fluid dynamical processes, we consider a non-rotating and non-magnetic slurry comprised of a single chemical component with a temperature that is tied to the liquidus. We study one-dimensional solutions in a configuration set up to mimic Earth's F-layer, varying gravitational strength $R$, the solid/liquid viscosity ratio $\lambda _{\mu }$ and the interaction parameter $K$, which measures friction between the phases. We develop scalings describing behaviour in the limit $R \gg 1$ and $\lambda _{\mu } \gg 1$, which are in excellent agreement with our numerical results. Application to Earth's core, where $R \sim 10^{28}$ and $\lambda _{\mu } \sim 10^{22}$, suggests that a pure iron slurry F-layer would contain a mean solid fraction of at most 5 %.
The contemporary crisis in relation to constitutional literacy relates not to the lack of knowledge that citizens possess about fundamental constitutional texts, but to the considerable lack of development in relation to what constitutional literacy itself entails. This article accordingly unpacks the notion of constitutional literacy: its importance, its characteristics, and its variable nature. Using a comparative lens, the article invites reflection on the role we expect citizens to play in our democracies, and especially the associated knowledge and skills required for successful state performance. We suggest that constitutional literacy is exceptionally multifaceted and fluid in nature, which serves to make its conceptualization and measurement challenging endeavours, and certainly more so than the easy invocation of this notion may assume at first blush. In this regard, engaging with the constitutional text, while an integral component of constitutional literacy, is ultimately only one part of the puzzle.
Background:Candida auris is a frequently drug-resistant yeast that can cause invasive disease and is easily transmitted in healthcare settings. Pediatric cases are rare in the United States, with <10 reported before 2022. In August 2021, the first C. auris case in Las Vegas was identified in an adult. By May 2022, 117 cases were identified across 16 healthcare facilities, including 3 pediatric cases at an acute-care hospital (ACH) with adult cases, representing the first pediatric cluster in the United States. The CDC and Nevada Division of Public and Behavioral Health (NVDPBH) sought to describe these cases and risk factors for C. auris acquisition. Methods: We defined a case as a patient’s first positive C. auris specimen. We reviewed medical records and infection prevention and control (IPC) practices. Environmental sampling was conducted on high-touch surfaces throughout affected adult and pediatric units. Isolate relatedness was assessed using whole-genome sequencing (WGS). Results: All 3 pediatric patients were born at the facility and had congenital heart defects. All were aged <6 months when they developed C. auris bloodstream infections; 2 developed C. auris endocarditis. One patient died. Patients overlapped in the pediatric cardiac intensive care unit; 2 did not leave between birth and C. auris infection. Mobile medical equipment was shared between adult and pediatric patients; lapses in cleaning and disinfection of shared mobile medical equipment and environmental surfaces were observed, presenting opportunities for transmission. Overall, 32 environmental samples were collected, and C. auris was isolated from 2 specimens from an adult unit without current cases. One was a composite sample from an adult patient’s bed handles, railings, tray table and call buttons, and the second was from an adult lift-assistance device. WGS of specimens from adult and pediatric cases and environmental isolates were in the same genetic cluster, with 2–10 single-nucleotide polymorphisms (SNPs) different, supporting within-hospital transmission. The pediatric cases varied by 0–3 SNPs; at least 2 were highly related. Conclusions:C. auris was likely introduced to the pediatric population from adults via inadequately cleaned and disinfected mobile medical equipment. We made recommendations to ensure adequate cleaning and disinfection and implement monitoring and audits. No pediatric cases have been identified since. This investigation demonstrates transmission can occur between unrelated units and populations and that robust infection prevention and control practices throughout the facility are critical for reducing C. auris environmental burden and limiting transmission, including to previously unaffected vulnerable populations, like children.
Objectives: To address the importation of multi-drug-resistant organisms (MDROs) when a colonized or infected patient is transferred from another VA facility, the Veterans Health Administration (VHA) launched the Inpatient Pathogen Tracker (IPT) in 2020. IPT tracks MDRO-infected/colonized patients and alerts MDRO Program Coordinators (MPCs) and Infection Preventionists (IPs) when such patients are admitted to their facility to facilitate rapid identification and isolation of infected/colonized patients. IPT usage has been low during initial rollout (32.5%). The VHA and the CARRIAGE QUERI Program developed targeted implementation strategies to increase utilization of IPT’s second iteration, VA Bug Alert (VABA). Methods: Familiarity with IPT was assessed via pre-education survey (3/2022). All sites received standard VABA implementation including: 1) adaptation of VABA features based on end-user feedback (completed 4/2022), 2) development and delivery of an educational module regarding the revised tool (completed 4/2022), and 3) internal facilitation from the VHA MDRO Program Office (ongoing) (see Figure for all key timepoints). Intent to register for VABA was assessed via post-education survey (4-5/2022). Sites (125 eligible) not registered for VABA by 6/1/2022 were randomly assigned to receive one of two conditions from 6/2022–8/2022: continued standard implementation alone or enhanced implementation. Enhanced implementation added the following to standard implementation: 1) audit and feedback reports and 2) external facilitation, including interviews and education about VABA. We compared the number of sites with ≥1 MPC/IP registered for VABA to-date between implementation conditions. Results:Pre-education survey. 168 MPC/IPs across 117 sites responded (94% of eligible sites). Among respondents, 25% had used IPT, 35.1% were familiar with but had not used IPT, and 39.9% were unfamiliar with IPT. Post-education survey. 93 MPC/IPs across 80 sites responded (59% of eligible sites). Of these, 81.7% said they planned to register for VABA, 4.3% said they would not register, and 14.0% said they were unsure. Post-6/1/2022 Registrations. By 6/1/2022, 71% of sites had ≥1 registered VABA user. Of the 28 unregistered sites eligible for enhanced implementation, thirteen were assigned to receive enhanced implementation, and fifteen were assigned to receive continued standard implementation. Eight sites in the enhanced implementation condition (61.5%) registered for VABA. Seven standard-implementation-only sites (46.7%) registered. The number of registered sites did not significantly differ by implementation condition (Fisher’s exact p=0.476). Conclusions: Standard and enhanced implementation were equally effective at encouraging VABA registration, suggesting that allocating resources to enhanced implementation may not be necessary.
Humans operating in extreme environments often conduct their operations at the edges of the limits of human performance. Sometimes, they are required to push these limits to previously unattained levels. As a result, their margins for error in execution are much smaller than that found in the general public. These same small margins for error that impact execution may also impact risk, safety, health, and even survival. Thus, humans operating in extreme environments have a need for greater refinement in their preparation, training, fitness, and medical care. Precision medicine (PM) is uniquely suited to address the needs of those engaged in these extreme operations because of its depth of molecular analysis, derived precision countermeasures, and ability to match each individual (and his or her specific molecular phenotype) with any given operating context (environment). Herein, we present an overview of a systems approach to PM in extreme environments, which affords clinicians one method to contextualize the inputs, processes, and outputs that can form the basis of a formal practice. For the sake of brevity, this overview is focused on molecular dynamics, while providing only a brief introduction to the also important physiologic and behavioral phenotypes in PM. Moreover, rather than a full review, it highlights important concepts, while using only selected citations to illustrate those concepts. It further explores, by demonstration, the basic principles of using functionally characterized molecular networks to guide the practical application of PM in extreme environments. At its core, PM in extreme environments is about attention to incremental gains and losses in molecular network efficiency that can scale to produce notable changes in health and performance. The aim of this overview is to provide a conceptual overview of one approach to PM in extreme environments, coupled with a selected suite of practical considerations for molecular profiling and countermeasures.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
Methods
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Results
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Conclusions
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
In the first half of the twentieth century, deaths from infectious disease, especially among the very young, fell dramatically in American cities. However, as infant mortality fell and life expectancy rose, racial inequality in urban infectious disease mortality grew. In this paper, we show that the fall in mortality and the rise in racial inequality in mortality reflected two countervailing processes. The dramatic decline in infant mortality from waterborne diseases drastically reduced the total urban infectious disease mortality rate of both Black and white Americans while having a comparatively small effect on the total racial disparity in urban infectious disease mortality. In contrast, the unequal fall in tuberculosis mortality, particularly in the prime of life, widened racial inequality in infectious disease mortality in US cities.