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1.
J Adolesc Health ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38727658

RESUMO

PURPOSE: This study aimed to determine whether the modified Screening to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol, and Drugs (BSTAD) that included e-cigarettes/vaping as examples could identify all nicotine and cannabis use or whether additional questions specifically about vaping are needed. METHODS: Between July 2020 and February 2022, adolescents recruited from primary care or an outpatient adolescent substance use disorder program were randomized to complete S2BI or BSTAD followed by specific questions about vaping. Screen questions were updated to include "vaping" in the parenthetical examples of nicotine and cannabis use. RESULTS: Data from 502 adolescent participants who completed both the S2BI or BSTAD and vaping questions were analyzed. The S2BI and BSTAD identified 92% (23/25) and 100% (16/16) of nicotine vaping and 100% (16/16) and 95.5% (21/22) of cannabis vaping, respectively. DISCUSSION: The S2BI and BSTAD tools accurately identify nicotine and cannabis use without specific questions about vaping.

2.
Health Commun ; : 1-19, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742648

RESUMO

This systematic review evaluates health messaging strategies for the prevention and cessation of e-cigarette use among youth and young adults. Health messaging strategies were defined as the strategic process of developing messages with the intent to shape, reinforce, or change recipients' health attitudes and behaviors. McGuire's Communication/Persuasion Model guided the analysis of the messaging strategies, focusing on the model's five communication inputs (i.e. source, message, channel, audience, destination) and 14 persuasive outcomes. Nine databases were searched from January 2007 to September 2023. The inclusion criteria encompassed studies in English that presented quantitative data on messaging strategies aimed at discouraging vaping among youth and young adults. Each study was also coded for study characteristics and the utilization of theory. Out of 6,045 studies, 25 met the inclusion criteria. The reviewed studies exhibit a diverse array of research methods and a consistent integration of theories. The review emphasizes the nuanced main and interaction effects of various communication inputs, such as message features and audience characteristics, while also pointing out a research gap in message sources. In addition, the utilization of social media for effective messaging to engage the audience requires further research. Only one study specifically evaluated messaging strategies for vaping cessation. More research is imperative to develop targeted and tailored messages that effectively prevent and reduce vaping, especially among populations at higher risk of vaping-related harms, while also leveraging effective channels and innovative communication technologies to engage the audience.

3.
PLOS Glob Public Health ; 4(5): e0002609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696500

RESUMO

Household-based tuberculosis (TB) contact evaluation may be an efficient strategy to reach people who could benefit from oral pre-exposure prophylaxis (PrEP) because of the epidemiological links between HIV and TB. This study estimated the number of HIV serodifferent couples in TB-affected households and potential HIV acquisitions averted through their PrEP use in 4 TB-HIV high-burden countries. We conducted a model-based analysis set in Ethiopia, Kenya, South Africa, and Uganda using parameters from population-based household surveys, systematic literature review and meta-analyses, and estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We parameterized the nonlinear relationship between the proportion of serodifferent couples among people living with HIV and population-level HIV prevalence using Markov chain Monte Carlo methods. We integrated all parameters in a mathematical model and propagated uncertainty using a Monte Carlo approach. We estimated the HIV prevalence among adults aged 15-49 living in TB-affected households to be higher than in the general population in all 4 countries. The proportion of serodifferent couples among all couples in TB-affected households was also higher than in the general population (South Africa: 20.7% vs. 15.7%, Kenya: 15.7% vs. 5.7%, Uganda: 14.5% vs. 6.0%, Ethiopia: 4.1% vs. 0.8%). We estimated that up to 1,799 (95% UI: 1,256-2,341) HIV acquisitions in South Africa could be prevented annually by PrEP use in serodifferent couples in TB-affected households, 918 (95% UI: 409-1,450) in Kenya, 686 (95% UI: 505-871) in Uganda, and 408 (95% UI: 298-522) in Ethiopia. As couples in TB-affected households are more likely to be serodifferent than couples in the general population, offering PrEP during household TB contact evaluation may prevent a substantial number of HIV acquisitions.

4.
Contrib Mineral Petrol ; 179(5): 52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686218

RESUMO

The aluminous calcium-ferrite type phase (CF) and new aluminous phase (NAL) are thought to hold the excess alumina produced by the decomposition of garnet in MORB compositions in the lower mantle. The respective stabilities of CF and NAL in the nepheline-spinel binary (NaAlSiO4-MgAl2O4) are well established. However with the addition of further components the phase relations at lower mantle conditions remain unclear. Here we investigate a range of compositions around the nepheline apex of the nepheline-kalsilite-spinel compositional join (NaAlSiO4-KAlSiO4-MgAl2O4) at 28-78 GPa and 2000 K. Our experiments indicate that even small amounts of a kalsilite (KAlSiO4) component dramatically impact phase relations. We find NAL to be stable up to at least 71 GPa in potassium-bearing compositions. This demonstrates the stabilizing effect of potassium on NAL, because NAL is not observed at pressures above 48 GPa on the nepheline-spinel binary. We also observe a broadening of the CF stability field to incorporate larger amounts of potassium with increasing pressure. For pressures below 50 GPa only minor amounts (<0.011(1)KK+Na+Mg) of potassium are soluble in CF, whereas at 68 GPa, we find a solubility in CF of at least 0.088(3)KK+Na+Mg. This indicates that CF and NAL are suitable hosts of the alkali content of MORB compositions at lower mantle conditions. For sedimentary compositions at lower mantle pressures, we expect K-Hollandite to be stable in addition to CF and NAL for pressures of 28-48 GPa, based on our simplified compositions. Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-024-02129-w.

5.
Nurse Educ ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564703

RESUMO

BACKGROUND: Due to the nursing faculty shortage, expert clinical nurses are working as novice clinical instructors (CIs). Orientation is needed to prepare these nurses to teach; however, lack of evidence-based guidelines for orientation programs can lead to variability among institutions. PURPOSE: The purpose of this study was to describe clinical nursing faculty orientation practices in the United States. METHODS: A descriptive convergent mixed methods design was used. RESULTS: One hundred thirteen CIs participated. Of these, 70.8% were not provided with a formal orientation to their role. Duration, modality, and content varied widely among orientations. Four themes were derived from the qualitative data: Administrative Requirements, Transition to Clinical Educator, Mentorship, and Resilience. CONCLUSIONS: Clinical faculty orientation practices vary widely in the United States. Evidence-based guidelines are needed to streamline orientations to provide CIs with the requisite knowledge and skills to support clinical students.

6.
Tob Control ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485232

RESUMO

BACKGROUND: Oral nicotine products (ONPs) are increasing in sales, availability and flavours. In April 2022, the US Food and Drug Administration (FDA) obtained regulatory authority over non-tobacco nicotine products, which include many ONPs. Advertising practices for ONPs need monitoring to understand marketing strategies and inform FDA marketing authorisation decisions. METHODS: ONP advertisement (ad) expenditure data (January 2016-June 2023) were purchased (print, TV, radio, online video, online display and mobile; N=125 236) and adjusted to 2023 dollars. Descriptive statistics examined expenditures by ONP brand and media outlet over time. RESULTS: Velo spent the most on ONP advertising (89.8%), followed by Zyn (5.7%) and Black Buffalo (1.2%). Velo encompassed the majority of TV (98.1%), radio (99.9%) and mobile ad spend (87.3%); Zyn was the leader for online display (46.2%) and online video (71.1%); and Black Buffalo accounted for 100% of print ads. In 2023, (January-June), Zyn accounted for 88.0% of ad expenditures and Velo spent $0, though the total amount spent by Zyn was far less than Velo in prior years. TV ads (98.1% Velo) aired primarily on prime time/late night or 09:00-17:00 on weekends. Radio ads (99.9% Velo) aired primarily from 06:00 to 10:00, 12:00 to 14:00 and 15:00 to 19:00 on weekdays. Overall, expenditures focused on reaching a national audience, though print ads indicated potential male-targeted marketing. CONCLUSIONS: Following FDA's regulatory authority over non-tobacco nicotine products, ad expenditures for Velo dropped to $0. Ongoing surveillance of ONP ad trends can inform FDA marketing authorisation decisions by revealing brand-specific marketing strategies that may be targeted toward populations at increased risk of tobacco use.

7.
Health Commun ; : 1-8, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478963

RESUMO

Health communication research applies communication science to develop generalizable knowledge capable of improving the health and well-being of individuals and communities. But to what extent does the knowledge generated by the health communication field actually achieve public health impact? To answer this question, we discuss the application of health communication science and research within a tobacco regulatory science framework. We describe three areas in which health communication research funded by the Food and Drug Administration (FDA) Center for Tobacco Products (CTP) contributed to 1) youth tobacco prevention campaigns, 2) cigarette health warnings, and 3) regulation of labeling, advertising, and marketing claims. These examples demonstrate how communication regulatory science achieves public health impact in the real world by informing national policies, regulatory actions, and public health practice.

8.
Addict Behav ; 152: 107982, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38359494

RESUMO

BACKGROUND: Flavored novel oral nicotine products (ONP), such as pouches, gum, lozenges, tablets, and gummies, have recently entered the US market but have not been authorized for smoking cessation. This study assessed the prevalence and correlates of ONPs in a national sample of youth who smoked little filtered cigars or cigarillos (LCCs) or were susceptible to LCCs. METHODS: We conducted a national online survey from September-October 2022, as part of a study to develop cigar warnings among youth. Those aged 15-20 years old who reported using (ever or current) or susceptibility to little filtered cigars or cigarillos (LCCs) were eligible. Descriptive statistics and chi-square analyses assessed the prevalence of flavored ONP use and associations with other past 30-day tobacco product use and participant characteristics. RESULTS: Approximately one-fifth (17.1 %) of the sample (n = 680) reported past month flavored ONP use. Any past month tobacco use was correlated with past month flavored ONP use (ps < 0.001), increasing from 17.1 % in the overall sample to 26.8 % among those reporting e-cigarette use, 41.4 % (LCCs), 47.8 % (waterpipe tobacco), 61.8 % (large cigars), and 69.1 % (smokeless tobacco). The number of products used in the past month was significantly associated with higher odds of ONPs in the past month in a multivariable logistic regression model (aOR2.26; 95 % CI: 1.92, 2.65). DISCUSSION: Almost one-fifth of participants who use or are susceptible to cigar use in our national sample of youth use ONPs. Dual/poly use of other tobacco products and ONPs among youth suggests that many of these youth may be addicted to nicotine. Additional surveillance and regulation of ONPs that exhibit enticing characteristics, such as flavors, kid-friendly formulations, and targeted marketing/branding may be needed.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Adolescente , Adulto Jovem , Adulto , Nicotina , Prevalência , Fumar/epidemiologia
9.
Nature ; 626(8001): 957-958, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38418908
10.
JAMA Netw Open ; 7(2): e2354467, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38306102

RESUMO

This cohort study reports the rate and degree of compliance with the Food and Drug Administration­mandated warning labels among waterpipe tobacco brands and products.


Assuntos
Tabaco para Cachimbos de Água , Humanos , Embalagem de Produtos , Rotulagem de Produtos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38385864

RESUMO

The microtubule cytoskeleton is a major structural element inside cells that directs self-organization using microtubule-associated proteins and motors. It has been shown that finite-sized, spindle-like microtubule organizations, called "tactoids," can form in vitro spontaneously from mixtures of tubulin and the antiparallel crosslinker, MAP65, from the MAP65/PRC1/Ase family. Here, we probe the ability of MAP65 to form tactoids as a function of the ionic strength of the buffer to attempt to break the electrostatic interactions binding MAP65 to microtubules and inter-MAP65 binding. We observe that, with increasing monovalent salts, the organizations change from finite tactoids to unbounded length bundles, yet the MAP65 binding and crosslinking appear to stay intact. We further explore the effects of ionic strength on the dissociation constant of MAP65 using both microtubule pelleting and single-molecule binding assays. We find that salt can reduce the binding, yet salt never negates it. Instead, we believe that the salt is affecting the ability of the MAP65 to form phase-separated droplets, which cause the nucleation and growth of tactoids, as recently demonstrated.

12.
Subst Use Addctn J ; 45(1): 54-64, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38258860

RESUMO

BACKGROUND: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with 0 declines attributable to e-cigarette (EC) use. Given that normative beliefs are associated with quitting and switching to ECs, we assessed cross-sectional associations between age, CC, and EC descriptive and injunctive norms and potential interactions with tobacco use behavior. METHODS: Data are from people with current, established (≥100 lifetime CCs) CC use (n = 8072) at Wave 5 (2018-2019) of the adult Population Assessment of Tobacco and Health Study. We used adjusted multivariable logistic regressions to model social norms as a function of age (18-24, 25-34, 35-44, 45-54, 55-64, ≥65 years). We also dichotomized age (≥55 vs 18-54) to investigate interactions between age and social norms on past 12-month CC quit attempts and past-month EC use. RESULTS: Older age was positively associated with pro- and anti-CC norms and anti-EC norms. Significant interactive effects revealed that being advised to quit smoking by a healthcare provider was more strongly associated with CC quit attempts among adults ≥55 years (adjusted odds ratio [aOR] [95% CI]: 2.12 [1.66, 2.71]) than adults <55 years (aOR: 1.63 [1.34, 2.00]). Reporting people close to you use ECs was also more strongly associated with EC use among adults ≥55 years (aOR: 4.37 [3.35, 5.69]) than among adults <55 years (aOR: 3.43 [2.89, 4.08]). CONCLUSIONS: This study identified modifiable risk factors for tobacco use that may be particularly beneficial for older adults. Behavioral and communication interventions that target normative beliefs may maximize smoking cessation, or harm reduction when cessation is not possible.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Idoso , Estudos Transversais , Uso de Tabaco/epidemiologia
13.
ArXiv ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36911279

RESUMO

Active biological molecules present a powerful, yet largely untapped, opportunity to impart autonomous regulation to materials. Because these systems can function robustly to regulate when and where chemical reactions occur, they have the ability to bring complex, life-like behavior to synthetic materials. Here, we achieve this design feat by using functionalized circadian clock proteins, KaiB and KaiC, to engineer time-dependent crosslinking of colloids. The resulting material self-assembles with programmable kinetics, producing macroscopic changes in material properties, via molecular assembly of KaiB-KaiC complexes. We show that colloid crosslinking depends strictly on the phosphorylation state of KaiC, with kinetics that are synced with KaiB-KaiC complexing. Our microscopic image analyses and computational models indicate that the stability of colloidal super-structures depends sensitively on the number of Kai complexes per colloid connection. Consistent with our model predictions, a high concentration stabilizes the material against dissolution after a robust self-assembly phase, while a low concentration allows circadian oscillation of material structure. This work introduces the concept of harnessing biological timers to control synthetic materials; and, more generally, opens the door to using protein-based reaction networks to endow synthetic systems with life-like functional properties.

14.
Nicotine Tob Res ; 26(4): 512-516, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-37819722

RESUMO

INTRODUCTION: Many people remove the tobacco leaf from cigars and replace it with cannabis (ie, blunts), but few studies have examined whether messages about the risks of cigars, like warnings on cigar packages, can affect blunt use. METHODS: Participants were 438 U.S. adults who reported past 30-day cigar use and ever blunt use, recruited from a probability-based national panel to take an online survey. In a 2 × 2 experiment with a between-subjects design, we manipulated two cigar warning characteristics: (1) warning type: text-only versus pictorial (ie, text + image) and (2) warning size: 30% (smaller) versus 50% (larger) of the product package. Participants then viewed six different warnings on a fictious cigarillo package, within their randomly assigned condition. After evaluating all stimuli, participants were asked the extent to which the warnings discouraged them from wanting to use cigars to smoke cannabis (ie, blunt perceived warning effectiveness). Response options ranged from "not at all" (1) to "a great deal" (5). RESULTS: We observed no main effects of warning type or size on blunt perceived warning effectiveness. However, a significant interaction existed between the two experimental manipulations (p = .009). Whereas adding images made no difference to blunt perceived warning effectiveness when warnings were smaller (simple effect: -0.22, p = .28), images mattered for larger warnings. Specifically, adding images increased blunt perceived warning effectiveness when warnings were 50% of the product package (simple effect: 0.52, p = .008). CONCLUSIONS: This experiment provides preliminary evidence that larger pictorial cigar warnings may discourage blunt use relative to larger but text-only warnings. IMPLICATIONS: Blunts, which are hollowed out cigars with tobacco leaf wrappers that are filled with cannabis leaf, are one of the most common ways in which tobacco and cannabis are used simultaneously, yet few studies have examined whether messages about the risks of cigars can affect blunt use. We conducted an online experiment concerning the perceived effectiveness of cigar warnings among people who use blunts recruited from a probability-based panel. Results provide novel, preliminary evidence that larger pictorial cigar warnings may discourage blunt use, relative to larger but text-only warnings. More research evaluating cigar warnings on blunt use is needed.


Assuntos
Cannabis , Rotulagem de Produtos , Produtos do Tabaco , Adulto , Humanos , Rotulagem de Produtos/métodos , Inquéritos e Questionários
15.
AJPM Focus ; 3(1): 100155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38130803

RESUMO

Introduction: The COVID-19 pandemic continues with highly contagious variants and waning immunity. As the virus keeps evolving to be more infectious and immune evasive, some question whether the COVID-19 pandemic can be managed through sustainable public health measures. Methods: We developed an agent-based simulation to explore the impact of COVID-19 mutations, periodic vaccinations, and nonpharmaceutical interventions on reducing COVID-19 deaths. The model is calibrated to the greater Seattle area by observing local epidemic data. We perform scenario analyses on viral mutations that change infectiousness, disease severity, and immune evasiveness from previous infections and vaccination every 6 months. The simulation is run until the end of year 2023. Results: Variants with increased infectivity or increased immune evasion dominate previous strains. With enhanced immune protection from a pancoronavirus vaccine, the most optimistic periodic vaccination rate reduces average total deaths by 44.6% compared with the most pessimistic periodic vaccination rate. A strict threshold nonpharmaceutical intervention policy reduces average total deaths by 71.3% compared with an open society, whereas a moderate nonpharmaceutical intervention policy results in a 33.6% reduction. Conclusions: Our findings highlight the potential benefits of pancoronavirus vaccines that offer enhanced and longer-lasting immunity. We emphasize the crucial role of nonpharmaceutical interventions in reducing COVID-19 deaths regardless of virus mutation scenarios. Owing to highly immune evasive and contagious SARS-CoV-2 variants, most scenarios in this study fail to reduce the mortality of COVID-19 to the level of influenza and pneumonia. However, our findings indicate that periodic vaccinations and a threshold nonpharmaceutical intervention policy may succeed in achieving this goal. This indicates the need for caution and vigilance in managing a continuing COVID-19 epidemic.

16.
Eur Phys J E Soft Matter ; 46(12): 134, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127202

RESUMO

Active, motor-based cargo transport is important for many cellular functions and cellular development. However, the cell interior is complex and crowded and could have many weak, non-specific interactions with the cargo being transported. To understand how cargo-environment interactions will affect single motor cargo transport and multi-motor cargo transport, we use an artificial quantum dot cargo bound with few (~ 1) to many (~ 5-10) motors allowed to move in a dense microtubule network. We find that kinesin-driven quantum dot cargo is slower than single kinesin-1 motors. Excitingly, there is some recovery of the speed when multiple motors are attached to the cargo. To determine the possible mechanisms of both the slow down and recovery of speed, we have developed a computational model that explicitly incorporates multi-motor cargos interacting non-specifically with nearby microtubules, including, and predominantly with the microtubule on which the cargo is being transported. Our model has recovered the experimentally measured average cargo speed distribution for cargo-motor configurations with few and many motors, implying that numerous, weak, non-specific interactions can slow down cargo transport and multiple motors can reduce these interactions thereby increasing velocity.


Assuntos
Citoesqueleto , Cinesinas , Microtúbulos
17.
Eur Phys J E Soft Matter ; 46(11): 109, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37947921

RESUMO

Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network. Using the experimental data, we deduced parameters for cargo detachment at intersections and away from intersections, allowing us to create an analytical theory for the run length as a function of mesh size. We also used these parameters to perform simulations of cargoes along paths extracted from the experimental networks. We find excellent agreement between the trends in run length, displacement, and trajectory persistence length comparing the experimental and simulated trajectories.

18.
Health Commun ; : 1-12, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37937858

RESUMO

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1). Based on survey findings, we selected a message focused on nicotine and brain development for the point-of-sale trial (Phase 2). We then conducted a cluster-randomized trial at six gas stations with convenience stores, randomly assigned to the intervention (messages displayed) or no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 participants (ages 16-25) per store, at baseline and a four-week follow-up. Phase 1 included 1,636 participants in the online study. Intervention messages were rated as more attention grabbing than plain text messages (p < .05), though were rated similarly on other outcomes. Exposure to intervention messages resulted in larger changes from pre- to posttest for beliefs about addiction and relative harms versus cigarettes (p < .05). Phase 2 included 586 participants in the point-of-sale study. Real-world campaign exposure was low (31.8%), and no differences were found between conditions. E-cigarette prevention messages focused on nicotine's impact on brain development show promise. However, garnering attention for communication campaigns in saturated point-of-sale environments, often dominated by tobacco advertising, is challenging. Future efforts should utilize additional communication channels to directly target adolescents and young adults.

19.
medRxiv ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37662260

RESUMO

Introduction: Antiretroviral therapy (ART) and TB preventive treatment (TPT) both prevent tuberculosis (TB) disease and deaths among people living with HIV. Differentiated care models, including community-based care, can increase uptake of ART and TPT to prevent TB in settings with a high burden of HIV-associated TB, particularly among men. Methods: We developed a gender-stratified dynamic model of TB and HIV transmission and disease progression among 100,000 adults ages 15-59 in KwaZulu-Natal, South Africa. We drew model parameters from a community-based ART initiation and resupply trial in sub-Saharan Africa (Delivery Optimization for Antiretroviral Therapy, DO ART) and other scientific literature. We simulated the impacts of community-based ART and TPT care programs during 2018-2027, assuming that community-based ART and TPT care were scaled up to similar levels as in the DO ART trial (i.e., ART coverage increasing from 49% to 82% among men and from 69% to 83% among women) and sustained for ten years. We projected the number of TB cases, deaths, and disability-adjusted life years (DALYs) averted relative to standard, clinic-based care. We calculated program costs and incremental cost-effectiveness ratios from the provider perspective. Results: If community-based ART care could be implemented with similar effectiveness to the DO ART trial, increased ART coverage could reduce TB incidence by 27.0% (range 21.3% - 34.1%) and TB mortality by 36.0% (range 26.9% - 43.8%) after ten years. Increasing both ART and TPT uptake through community-based ART with TPT care could reduce TB incidence by 29.7% (range 23.9% - 36.0%) and TB mortality by 36.0% (range 26.9% - 43.8%). Community-based ART with TPT care reduced gender disparities in TB mortality rates by reducing TB mortality among men by a projected 39.8% (range 32.2% - 46.3%) and by 30.9% (range 25.3% - 36.5%) among women. Over ten years, the mean cost per DALY averted by community-based ART with TPT care was $846 USD (range $709 - $1,012). Conclusions: By substantially increasing coverage of ART and TPT, community-based care for people living with HIV could reduce TB incidence and mortality in settings with high burdens of HIV-associated TB and reduce TB gender disparities.

20.
PNAS Nexus ; 2(8): pgad245, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37575673

RESUMO

The cellular cytoskeleton relies on diverse populations of motors, filaments, and binding proteins acting in concert to enable nonequilibrium processes ranging from mitosis to chemotaxis. The cytoskeleton's versatile reconfigurability, programmed by interactions between its constituents, makes it a foundational active matter platform. However, current active matter endeavors are limited largely to single force-generating components acting on a single substrate-far from the composite cytoskeleton in cells. Here, we engineer actin-microtubule (MT) composites, driven by kinesin and myosin motors and tuned by crosslinkers, to ballistically restructure and flow with speeds that span three orders of magnitude depending on the composite formulation and time relative to the onset of motor activity. Differential dynamic microscopy analyses reveal that kinesin and myosin compete to delay the onset of acceleration and suppress discrete restructuring events, while passive crosslinking of either actin or MTs has an opposite effect. Our minimal advection-diffusion model and spatial correlation analyses correlate these dynamics to structure, with motor antagonism suppressing reconfiguration and demixing, while crosslinking enhances clustering. Despite the rich formulation space and emergent formulation-dependent structures, the nonequilibrium dynamics across all composites and timescales can be organized into three classes-slow isotropic reorientation, fast directional flow, and multimode restructuring. Moreover, our mathematical model demonstrates that diverse structural motifs can arise simply from the interplay between motor-driven advection and frictional drag. These general features of our platform facilitate applicability to other active matter systems and shed light on diverse ways that cytoskeletal components can cooperate or compete to enable wide-ranging cellular processes.

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