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Background. People living with HIV (PWH) frequently have co-morbid substance use disorders that may have been impacted by the COVID-19 pandemic. This study examined associations between COVID-related stress and increased substance use among PWH in Washington State. Methods. Between August 2020 and March 2021, we conducted an online survey of 397 PWH in western Washington. Logistic regression was used to analyze associations between a COVID-19 stress score and four self-reported outcomes: increased alcohol use, increased cigarette smoking, increased marijuana use, and increased use of illicit substances. Results. Thirty-five (38.0%) of 92 participants who smoked, 61 (23.4%) of 261 participants who used alcohol, 15 (14.6%) of 103 participants who used marijuana, and 35 (33.0%) of 102 participants who used illicit substances reported increased use of these substances. Higher COVID-19 stress scores were associated with higher odds of increased cigarette smoking (adjusted odds ratio [aOR] = 1.15, 95% confidence interval [CI]: 1.04–1.27), even after adjustment for anxiety and depressive symptoms (aOR 1.14, 95%CI: 1.03–1.27). COVID-19 stress was not associated with an increased use of alcohol, marijuana, or illicit substances. Conclusions. COVID-19-related stress was associated with self-reported increased cigarette smoking among PWH in western Washington during the pandemic. [ABSTRACT FROM AUTHOR]

Background: Assisted partner services (APS) is a recommended public health approach to promote HIV testing for sexual partners of individuals diagnosed with HIV. We evaluated the cost and cost-effectiveness of integrating oral HIV self-testing (HIVST) into existing APS programs. Methods: Within the APS-HIVST study conducted in western Kenya (2021–2022), we conducted micro-costing, time-and-motion, and provider surveys to determine incremental HIVST distribution cost (2022 USD). Using a decision tree model, we estimated the incremental cost per new diagnosis (ICND) for HIVST incorporated into APS, compared to APS with provider-delivered testing only. Scenario, parameter and probabilistic sensitivity analyses were conducted to explore influential assumptions. Results: The cost per HIVST distributed within APS was USD 8.97, largest component costs were testing supplies (38%) and personnel (30%). Under conditions of a facility-based testing uptake of <91%, or HIVST utilization rates of <27%, HIVST integration into APS is potentially cost-effective. At a willing-to-pay threshold of USD 1000, the net monetary benefit was sensitive to the effectiveness of HIVST in increasing testing rates, phone call rates, HIVST sensitivity, HIV prevalence, cost of HIVST, space allocation at facilities, and personnel time during facility-based testing. In a best-case scenario, the HIVST option was cheaper by USD 3037 and diagnosed 11 more cases (ICND = 265.82). Conclusions: Implementers and policy makers should ensure that HIVST programs are implemented under conditions that guarantee efficiency by focusing on facilities with low uptake for provider-delivered facility-based testing, while deliberately targeting HIVST utilization among the few likely to benefit from remote testing. Additional measures should focus on minimizing costs relating to personnel and testing supplies. [ABSTRACT FROM AUTHOR]

We derived the metallicity profile of the Milky Way low-α disc population from 2 to 20 kpc from the Galactic centre in 1 Gyr age bins using the astroNN catalogue, and we show that it is highly structured, with a plateau between 4 and 7 kpc and a break at 10–12 kpc. We argue that these features result from the two main bar resonances, the corotation and the outer Lindblad resonance (OLR), respectively. We show that the break in the metallicity profile is most visible in stars having 7–8 Gyr, reaching an amplitude of about 0.4 dex, and it is the signpost of the position of the bar OLR. The bar formation was accompanied by an episode of radial migration triggered by it slowing down and it is responsible for spreading old metal-rich stars up to the OLR. The data show that the slowdown of the bar ended 6–7 Gyr ago. Based on numerical simulations that reproduce well the characteristic break observed in the metallicity profile, we argue that this implies that the bar formed in our Galaxy 8–10 Gyr ago. Analysis of the metallicity distribution as a function of radius shows no evidence of significant systematic outward radial migration after this first episode. We argue that the variation of the metallicity dispersion as a function of the guiding radius is dominated by the migration triggered by the bar, but also that the libration of orbits around the bar resonances induces a mixing that may have a significant impact on the observed metallicity dispersion. In contrast, the absence of a break in the metallicity profile of populations younger than ∼6 Gyr and the flattening of the gradient at younger ages is interpreted as evidence that the strength of the bar has decreased, loosening its barrier effect and allowing the gas and metals on both sides of the OLR to mix, erasing the break. Beyond the OLR, stars younger than 7 Gyr show very small metallicity dispersion, suggesting that no or limited mixing induced by the spiral arms has occurred in the outer disc. [ABSTRACT FROM AUTHOR]

Objective: To compare preferences, uptake, and cofactors for unassisted home-based oral self-testing (HB-HIVST) versus clinic-based rapid diagnostic blood tests (CB-RDT) for maternal HIV retesting. Design: Prospective cohort. Methods: Between November 2017 and June 2019, HIV-negative pregnant Kenyan women receiving antenatal care were enrolled and given a choice to retest with HB-HIVST or CB-RDT. Women were asked to retest between 36 weeks gestation and 1-week post-delivery if the last HIV test was <24 weeks gestation or at 6 weeks postpartum if ≥24 weeks gestation, and self-report on retesting at a 14-week postpartum. Results: Overall, 994 women enrolled and 33% (n = 330) selected HB-HIVST. HB-HIVST was selected because it was private (n = 224, 68%), convenient (n = 211, 63%), and offered flexibility in the timing of retesting (n = 207, 63%), whereas CB-RDT was selected due to the trust of providers to administer the test (n = 510, 77%) and convenience of clinic testing (n = 423, 64%). Among 905 women who reported retesting at follow-up, 135 (15%) used HB-HIVST. Most (n = 595, 94%) who selected CB-RDT retested with this strategy, compared to 39% (n = 120) who selected HB-HIVST retesting with HB-HIVST. HB-HIVST retesting was more common among women with higher household income and those who may have been unable to test during pregnancy (both retested postpartum and delivered <37 weeks gestation) and less common among women who were depressed. Most women said they would retest in the future using the test selected at enrollment (99% [n = 133] HB-HIVST; 93% [n = 715] CB-RDT-RDT). Conclusions: While most women preferred CB-RDT for maternal retesting, HB-HIVST was acceptable and feasible and could be used to expand HIV retesting options. [ABSTRACT FROM AUTHOR]

Limited literature exists on chloramphenicol's clinical use. In this retrospective, single-center case-series, we examined 183 chloramphenicol-treated and 81 piperacillin-tazobactam-treated medical patients. Chloramphenicol recipients were older, more debilitated, cognitively impaired, and penicillin allergic, while increased need for inotropics, higher leukocyte count, and higher creatinine levels were notable in the piperacillin-tazobactam group. Pneumonia was the most common indication, with no mortality difference between groups. While acknowledging its antimicrobial activity and potential benefit in specific conditions such as pneumonia, further clinical studies are needed to assess the role of chloramphenicol in the setting where other alternatives are available. [ABSTRACT FROM AUTHOR]

Introduction: Assisted partner services (APS) is an effective strategy for increasing HIV testing, new diagnosis, and linkage to care among sexual partners of people living with HIV (PLWH). APS can be resource intensive as it requires community tracing to locate each partner named and offer them testing. There is limited evidence for the effectiveness of offering HIV self‐testing (HIVST) as an option for partner testing within APS. Methods: We conducted a cluster randomized controlled trial comparing provider‐delivered HIV testing (Standard APS) versus offering partners the option of provider‐delivered testing or HIVST (APS+HIVST) at 24 health facilities in Western Kenya. Facilities were randomized 1:1 and we conducted intent‐to‐treat analyses using Poisson generalized linear mixed models to estimate intervention impact on HIV testing, new HIV diagnoses, and linkage to care. All models accounted for clustering at the clinic level and new diagnoses and linkage models were adjusted for individual‐level age, sex, and income a priori. Results: From March to December 2021, 755 index clients received APS and named 5054 unique partners. Among these, 1408 partners reporting a prior HIV diagnosis were not eligible for HIV testing and were excluded from analyses. Of the remaining 3646 partners, 96.9% were successfully contacted for APS and tested for HIV: 2111 (97.9%) of 2157 in the APS+HIVST arm and 1422 (95.5%) of 1489 in the Standard APS arm. In the APS+HIVST arm, 84.6% (1785/2111) tested via HIVST and 15.4% (326/2111) received provider‐delivered testing. Overall, 16.7% of the 3533 who tested were newly diagnosed with HIV (APS+HIVST = 357/2111 [16.9%]; Standard APS = 232/1422 [16.3%]). Of the 589 partners who were newly diagnosed, 90.7% were linked to care (APS+HIVST = 309/357 [86.6%]; Standard APS = 225/232 [97.0%]). There were no significant differences between the two arms in HIV testing (relative risk [RR]: 1.02, 95% CI: 0.96–1.10), new HIV diagnoses (adjusted RR [aRR]: 1.03, 95% CI: 0.76–1.39) or linkage to care (aRR: 0.88, 95% CI: 0.74–1.06). Conclusions: There were no differences between APS+HIVST and Standard APS, demonstrating that integrating HIVST into APS continues to be an effective strategy for identifying PLWH by successfully reaching and HIV testing >95% of elicited partners, newly diagnosing with HIV one in six of those tested, >90% of whom were linked to care. Clinical Trial Number: NCT04774835 [ABSTRACT FROM AUTHOR]

Introduction: Assisted partner services (APS), or exposure notification and HIV testing for sexual partners of persons diagnosed HIV positive (index clients), is recommended by the World Health Organization. Most APS literature focuses on outcomes among index clients and their partners. There is little data on the benefits of providing APS to partners of partners diagnosed with HIV. Methods: We utilized data from a large‐scale APS implementation project across 31 facilities in western Kenya from 2018 to 2022. Females testing HIV positive at facilities were offered APS; those who consented provided contact information for all male sexual partners in the last 3 years. Male partners were notified of their potential HIV exposure and offered HIV testing services (HTS). Males newly testing positive were also offered APS and asked to provide contact information for their female partners in the last 3 years. Female partners of male partners (FPPs) were provided exposure notification and HTS. All participants with HIV were followed up at 12 months post‐enrolment to assess linkage‐to antiretroviral treatment (ART) and viral suppression. We compared HIV positivity, demographics and linkage outcomes among female index clients and FPPs. Results: Overall, 5708 FPPs were elicited from male partners, of whom 4951 received HTS through APS (87% coverage); 291 FPPs newly tested HIV positive (6% yield), an additional 1743 (35.2%) reported a prior HIV diagnosis, of whom 99% were on ART at baseline. At 12 months follow‐up, most FPPs were taking ART (92%) with very few adverse events: <1% reported intimate partner violence or reported relationship dissolution. FPPs were more likely than female index clients to report HIV risk behaviours including no condom use at last sex (45% vs. 30%) and multiple partners (38% vs. 19%). Conclusions: Providing HIV testing via APS to FPP is a safe and effective strategy to identify newly diagnosed females and achieve high linkage and retention to ART and can be an efficient means of identifying HIV cases in the era of declining HIV incidence. The high proportion of FPPs reporting HIV risk behaviours suggests APS may help interrupt community HIV transmission via increased knowledge of HIV status and linkage to treatment. [ABSTRACT FROM AUTHOR]

While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population. [ABSTRACT FROM AUTHOR]

This study measures changes in condomless anal sex (CAS) among HIV-negative men who have sex with men (MSM) who are not taking pre-exposure prophylaxis (PrEP). It considers the 2014–2019 cycles of the American Men's Internet Survey, a serial, cross-sectional web-based survey of US cisgender MSM aged ≥ 15 years, in which ~ 10% of each year's sample is drawn from the previous year. Among those surveyed for 2 years who remained HIV-negative and off PrEP, reports of having any CAS and of CAS partner number were compared across years. We disaggregated by partner HIV status, and considered demographic predictors. The overall population saw a significant 2.2 percentage-point (pp) increase in reports of any CAS year-over-year. Sub-populations with the largest year-on-year increases were 15–24-year-olds (5.0-pp) and Hispanic respondents (5.1-pp), with interaction (young Hispanic respondents = 12.8-pp). On the relative scale, these numbers correspond to 3.2%, 7.2%, 7.3% and 18.7%, respectively. Absolute increases were concentrated among partners reported as HIV-negative. Multivariable analyses for CAS initiation found effects concentrated among Hispanic and White youth and residents of fringe counties of large metropolitan areas. CAS partner number increases were similarly predicted by Hispanic identity and young age. Although condom use remains more common than PrEP use, increasing CAS among MSM not on PrEP suggests potential new HIV transmission pathways. Concentration of increases among 18–24-year-old MSM portends future increases in the proportion of newly diagnosed HIV that occur among youth. Concentration among young Hispanic MSM will likely expand existing disparities. Although reducing barriers to PrEP remains vital, condom promotion for MSM remains a key public health practice and appears to be missing key audiences. LGBTQ+-inclusive sex education is one avenue for enhancing these efforts. [ABSTRACT FROM AUTHOR]

Ethyl cellulose–ethanol (ECE) is emerging as a promising formulation for ablative injections, with more controllable injection distributions than those from traditional liquid ethanol. This study evaluates the influence of salient injection parameters on forces needed for infusion, depot volume, retention, and shape in a large animal model relevant to human applications. Experiments were conducted to investigate how infusion volume (0.5 mL to 2.5 mL), ECE concentration (6% or 12%), needle gauge (22 G or 27 G), and infusion rate (10 mL/h) impacted the force of infusion into air using a load cell. These parameters, with the addition of manual infusion, were investigated to elucidate their influence on depot volume, retention, and shape (aspect ratio), measured using CT imaging, in an ex vivo swine liver model. Force during injection increased significantly for 12% compared to 6% ECE and for 27 G needles compared to 22 G. Force variability increased with higher ECE concentration and smaller needle diameter. As infusion volume increased, 12% ECE achieved superior depot volume compared to 6% ECE. For all infusion volumes, 12% ECE achieved superior retention compared to 6% ECE. Needle gauge and infusion rate had little influence on the observed depot volume or retention; however, the smaller needles resulted in higher variability in depot shape for 12% ECE. These results help us understand the multivariate nature of injection performance, informing injection protocol designs for ablations using gel ethanol and infusion, with volumes relevant to human applications. [ABSTRACT FROM AUTHOR]

New strategic art is required to maneuver political economies to meet the demands of future engagements and campa igns. Cur rent d iscussions of the projec t ion of political-economic power are typically abstract, high-level, and policy-focused or present singular tactical actions as strategic actions, creating a gap for campaign practitioners. This article addresses the gap by drawing on Joint Planning, Joint Publication 5-0, and Joint Campaigns and Operations, Joint Publication 3-0, to further develop the concept and methodologies first int roduced in the author's earlier article "Multidimensionality: Rethinking Power Projection for the 21st Century." [ABSTRACT FROM AUTHOR]

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The Single-Port (SP) robotic system is increasingly being implemented in the United States, allowing for several minimally invasive urologic procedures to be performed. The present study aims to describe our single-center experience since the adoption of the SP platform. We retrospectively collected and analyzed consecutive SP cases performed at a major teaching hospital in the Midwest (Rush University Medical Center) from December 2020 to December 2023. Demographic variables were collected. Surgical and pathological outcomes were analyzed in the overall cohort and for each type of procedure. The study timeframe was divided into two periods to assess the evolution of SP technical features over time. In total, 160 procedures were performed, with robot-assisted radical prostatectomy (RARP) being the most common (49.4%). Overall, 54.4% of the procedures were extraperitoneal, with a significantly higher adoption of this approach in the second half of the study period (30% vs 74.3%, p < 0.001). A “plus one” assistant port was adopted in 38.1% of cases, with a shift towards a “pure” single-port surgery in the most recent procedures (21.1% vs 76.7%, p < 0.001). The median LOS was 33.5 h (30–48), with a rate of any grade and CD ≥ 3 postoperative complications of 9.4% and 2.5%, respectively, and a 30-day readmission rate of 1.9%. SP robotic surgery can be safely and effectively implemented for various urologic procedures. With increasing experience, the SP platform allows shifting away from transperitoneal procedures, potentially minimizing postoperative pain, and shortening hospital stay and postoperative recovery. [ABSTRACT FROM AUTHOR]

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 μg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas. [ABSTRACT FROM AUTHOR]

Objective: To estimate the potential contributions of reported changes in frequency of penile-vaginal sex (PVS), condom use and STI screening to changes in gonorrhea and chlamydial diagnoses from 2012 to 2019. Methods: An agent-based model of the heterosexual population in the U.S. simulated the STI epidemics. Baseline was calibrated to 2012 diagnosis rates, testing, condom use, and frequency of PVS. Counterfactuals used behaviors from the 2017-2019 NSFG, and we evaluated changes in diagnosis and incidence rates in 2019. Results: Higher testing rates increased gonorrhea and chlamydia diagnosis by 14% and 13%, respectively, but did not reduce incidence. Declining frequency of PVS reduced the diagnosis rate for gonorrhea and chlamydia 6% and 3% respectively while reducing incidence by 10% and 9% respectively. Declining condom use had negligible impact on diagnosis and incidence. Conclusion: Understanding how changing behavior drives STI incidence is essential to addressing the growing epidemics. Changes in testing and frequency of PVS likely contributed to some, but not all, of the changes in diagnoses. More research is needed to understand the context within which changing sexual behavior and testing are occurring. [ABSTRACT FROM AUTHOR]

Introduction. Some medical centers and surgeons require patients to stop smoking cigarettes prior to elective orthopaedic surgeries in an effort to decrease surgical complications. Given higher rates of smoking among rural individuals, rural patients may be disproportionately impacted by these requirements. We assessed the perceptions and experiences of rural-residing Veterans and clinicians related to this requirement. Methods. We conducted qualitative semistructured one-on-one interviews of 26 rural-residing veterans, 10 VA orthopaedic surgery staff (from two Veterans Integrated Services Networks), 24 PCPs who serve rural veterans (14 VA; 10 non-VA), and 4 VA pharmacists. Using the knowledge, attitudes, and behavior framework, we performed conventional content analysis. Results. We found three primary themes across respondents: (1) knowledge of and the evidence base for the requirement varied widely; (2) strong personal attitudes toward the requirement; and (3) implementation and possible implications of this requirement. All surgery staff reported knowledge of requirements at their institution. VA PCPs reported knowledge of requirements but typically could not recall specifics. Most patients were unaware. The majority of respondents felt this requirement could increase motivation to quit smoking. Some PCPs felt a more thorough explanation of smoking-related complications would result in increased quit attempts. About half of all patients reported belief that the requirement was reasonable regardless of initial awareness. Respondents expressed little concern that the requirement might increase rural-urban disparities. Most PCPs and patients felt that there should be exceptions for allowing surgery, while surgical staff disagreed. Discussion. Most respondents thought elective surgery was a good motivator to quit smoking; but patients, PCPs, and surgical staff differed on whether there should be exceptions to the requirement that patients quit preoperatively. Future efforts to augment perioperative smoking cessation may benefit from improving coordination across services and educating patients more about the benefits of quitting. [ABSTRACT FROM AUTHOR]

Background: In Israel, internal medicine admissions are currently reimbursed without accounting for patient complexity. This is at odds with most other developed countries and has the potential to lead to market distortions such as avoiding sicker patients. Our objective was to apply a well-known, freely available risk adjustment model, the Elixhauser model, to predict relevant outcomes among patients hospitalized on the internal medicine service of a large, Israeli tertiary-care hospital. Methods: We used data from the Shaare Zedek Medical Center, a large tertiary referral hospital in Jerusalem. The study included 55,946 hospitalizations between 01.01.2016 and 31.12.2019. We modeled four patient outcomes: in-hospital mortality, escalation of care (intensive care unit (ICU) transfer, mechanical ventilation, daytime bi-level positive pressure ventilation, or vasopressors), 30-day readmission, and length of stay (LOS). We log-transformed LOS to address right skew. As is usual with the Elixhauser model, we identified 29 comorbid conditions using international classification of diseases codes, clinical modification, version 9. We derived and validated the coefficients for these 29 variables using split-sample derivation and validation. We checked model fit using c-statistics and R2, and model calibration using a Hosmer–Lemeshow test. Results: The Elixhauser model achieved acceptable prediction of the three binary outcomes, with c-statistics of 0.712, 0.681, and 0.605 to predict in-hospital mortality, escalation of care, and 30-day readmission respectively. The c-statistic did not decrease in the validation set (0.707, 0.687, and 0.603, respectively), suggesting that the models are not overfitted. The model to predict log length of stay achieved an R2 of 0.102 in the derivation set and 0.101 in the validation set. The Hosmer–Lemeshow test did not suggest issues with model calibration. Conclusion: We demonstrated that a freely-available risk adjustment model can achieve acceptable prediction of important clinical outcomes in a dataset of patients admitted to a large, Israeli tertiary-care hospital. This model could potentially be used as a basis for differential payment by patient complexity. [ABSTRACT FROM AUTHOR]

Current therapies for treating cervical dysplasia are often inaccessible in low and middle-income countries (LMICs), highlighting the need for novel low-cost therapies that can be delivered at the point of care. Ethanol ablation is a low-cost therapy designed to treat locoregional cancers, which we augmented into an ethyl cellulose (EC)-ethanol gel formulation to enhance its efficacy. Here, we evaluated whether EC-ethanol ablation is able to safely achieve an ablation zone comparable to thermocoagulation, a commonly used therapy for cervical dysplasia. The study was performed in 20 female Yorkshire pigs treated with either a single 500 µL injection of EC-ethanol into the 12 o'clock position of the cervix or a single application of thermocoagulation at 100 °C for 20 s. The average temperature, heart rate, respiratory rate, and blood oxygen remained within normal ranges throughout the EC-ethanol procedure and were similar to the thermocoagulation group. No major side effects were observed. The reproductive tracts were excised after 24 h to examine ablation zones. Comparable depths of necrosis were seen for EC-ethanol (18.6 ± 1.6 mm) and thermocoagulation (19.7 ± 4.1 mm). The volumes of necrosis induced by a single injection of EC-ethanol (626.2 ± 122.8 µL) were comparable to the necrotic volumes induced by thermocoagulation in the top half of the cervices (664.6 ± 168.5 µL). This suggests that two EC-ethanol injections could be performed (e.g., at the 12 and 6 o'clock positions) to achieve comparable total necrotic volumes to thermocoagulation and safely and effectively treat women with cervical dysplasia in LMICs. This is the first study to systematically evaluate EC-ethanol ablation in a large animal model and compare its safety and efficacy to thermocoagulation, a commonly used ablative therapy for cervical dysplasia. [ABSTRACT FROM AUTHOR]

Background: Diet quality photo navigation (DQPN) is a novel dietary intake assessment tool that was developed to help address limitations of traditional tools and to easily integrate into health care delivery systems. Prevailing practice is to validate new tools against approaches that are in wide use. Objective: This study aimed to assess 1) the validity of Diet ID in measuring diet quality, food group and nutrient intake against 2 traditional dietary assessment methods (i.e., food record [FR], food frequency questionnaire) and 2) the test reproducibility/reliability of Diet ID to obtain similar results with repeat assessments. Methods: Using a participant-sourcing platform for online research, we recruited 90 participants, 58 of whom completed DQPN, a 3-d FR (via the Automated Self-Administered 24-hour Dietary Assessment Tool), and a food frequency questionnaire (FFQ, via the Dietary History Questionnaire III). We estimated mean nutrient and food group intake with all 3 instruments and generated Pearson correlations between them. Results: Mean age (SD) of participants was 38 (11) y, and more than half were male (64%). The strongest correlations for DQPN when compared with the other 2 instruments were for diet quality, as measured by the Healthy Eating Index 2015; between DQPN and the FFQ, the correlation was 0.58 (P < 0.001), and between DQPN and the FR, the correlation was 0.56 (P < 0.001). Selected nutrients and food groups also showed moderate strength correlations. Test-retest reproducibility for measuring diet quality was evaluated for DQPN and showed a correlation of 0.70 (P < 0.0001). Conclusions: The current study offers evidence that DQPN is comparable to traditional dietary assessment tools for estimating overall diet quality. This performance, plus DQPN's ease-of-use and scalability, may recommend it in efforts to make dietary assessment a universal part of clinical care. [ABSTRACT FROM AUTHOR]

Reliance on water production by desalination as a solution to water scarcity is growing worldwide. High energy demands of seawater desalination raise new challenges for both water and energy management and highlight the importance of understanding the operational dependencies of the water sector on energy supplies. This study provides an in-depth analysis of the impact of the water-energy nexus in a desalination-based water sector, using Israel as a case study. Being large energy consumers, desalination plants are part of the Electricity Load Shedding Program (ELSP), which government energy regulators invoke in times of energy shortage. We focus on the interdependency between the two sectors as manifested at the time of ELSP utilization during an extreme heat wave. We show that energy shedding compensation is 6 to 14 times greater than the economic loss to the desalination plant from no water production, creating an obvious economic incentive to participate in ELSPs. However, this imbalance has a substantial negative impact on the water sector, which may compromise the level of service. Our evaluation concludes that the government authorities regulating water and energy need an official mechanism and policy for joint management strategies that can ensure economic efficiency and reduce the risk of power and water shortages during extreme events. [ABSTRACT FROM AUTHOR]

Introduction: SPI-62 is a small-molecule 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor exhibiting complicated nonlinear pharmacokinetics (PK) in human. Previously, we developed a target-mediated drug disposition (TMDD) model to characterize the substantial nonlinear PK of SPI-62. Objective: The aim of the current analysis was to perform population PK/PD analysis to further link SPI-62 exposure (i.e., PK) with its response (i.e., inhibition of hepatic HSD-1 activity) to gain a quantitative understanding of the SPI-62 dose-exposure-response relationship. Methods: PK and PD data from the first-in-human (FIH) clinical trials, including single ascending dose (SAD) and multiple ascending dose (MAD) studies, were used for model development. During the model development process, the final model selection was based on biological and physiological plausibility, goodness-of-fit plots, stability of parameter estimates, and objective function value. The nonlinear-mixed effect modeling (NONMEM) software was used for both the implementation of the PK/PD model and model simulation. SPI-62 plasma levels and hepatic HSD-1 inhibition over time following various dose regimens were simulated. Results: The final model was a two-compartment TMDD model component for SPI-62 and an inhibitory Imax model component for hepatic HSD-1 activity. The TMDD-hepatic PD model that we established adequately characterized all remarkable PK and PD behaviors of SPI-62, such as extremely low plasma exposures following the first low doses, nonlinear PK turned into linear PK after repeated low doses, and substantial and long-lasting hepatic HSD-1 inhibition following low doses. SPI-62 was estimated to bind to the target with a second-order association rate constant (Kon) of 8.43 nM−1 h−1 and first-order dissociation rate constant (Koff) value of 0.229 h−1, indicating that SPI-62 binds rapidly to, and dissociates slowly from, its pharmacological target. The estimated target capacity (Rtot) of 5460 nmol corresponds to approximately 2.2 mg of SPI-62, which comports well with the dose range in which PK nonlinearity is prominent. Model simulation results reveal that a 6 mg once-daily regimen can lead to long-lasting and substantial hepatic HSD-1 inhibition. Conclusions: A population TMDD-PD model that explains SPI-62 nonlinear PK and hepatic HSD-1 inhibition following different dose regimens in healthy adults was successfully established. Our simulation results provide a solid foundation for model-informed development of SPI-62. [ABSTRACT FROM AUTHOR]

To report a case of an optic disc granuloma secondary to sarcoidosis in the absence of any systemic symptoms nor evident signs of intraocular inflammation at the time of presentation. Retrospective case report A 59-year-old Caucasian woman with previously unrevealing systemic work up was referred to the uveitis service for persistent optic disc edema of the right eye for over 1 year. Fundoscopic examination revealed an optic disc granuloma with associated hyper-reflectivity on OCT and high surface reflectivity with medium internal reflectivity on B-scan ultrasound. CT chest was negative, however, a PET scan demonstrated extensive FDG activity in the mediastinum and bilateral hilum, consistent with a diagnosis of sarcoidosis. Optic nerve head granulomas can rarely present as the only clinical sign of sarcoidosis. In these cases, additional imaging modalities may be needed to make the appropriate diagnosis. [ABSTRACT FROM AUTHOR]

Water - A Resource Ripe for Conflict Water has a unique combination of qualities that contributes to the many conflicts with respect to its control and use. Water security is a critical aspect of climate change, human security, and sustainable development, particularly in regions and communities where competing water usage, climate change impacts, and cross-border water agreements contribute to conflicts. New Insights into Water and Conflict Prevention This Special Issue is dedicated to the continuation of this somewhat underdeveloped aspect of water conflict management: conflict prevention. [Extracted from the article]

HIV self-testing (HIVST) can improve testing completion among adolescents and young adults (AYA), although its influence on sexual behaviors is unclear. We evaluated whether HIVST was associated with changes in talking with sexual partners about HIVST, condom use, and HIV risk perception among AYA ages 15–24 years in a study of HIVST distribution through homes, pharmacies, and nightclubs in Nairobi, Kenya. All participants had negative HIVST results. Regression models were used to evaluate changes between pre-HIVST and 4 months post-HIVST. Overall, there was a significant increase in talking with sexual partners about HIVST. There was a significant reduction in number of condomless sex acts among AYA recruited through pharmacies and homes. Unexpectedly, among females, there was a significant decrease in consistent condom use with casual partners. HIVST services for AYA may benefit from including strategies to support condom use and partner communication about self-testing adapted to specific populations and partnerships. [ABSTRACT FROM AUTHOR]

Background: Patients admitted to internal medicine may be moved to more advanced-care settings when their condition deteriorates. In these advanced care settings, there may be higher levels of monitoring and greater ability to deliver Intensive Medical Treatments (IMTs). To the best of our knowledge, no previous study has examined the proportion of patients at different levels of care who receive different types of IMTs. Methods: In this retrospective observational cohort study, we examined data from 56,002 internal medicine hospitalizations at Shaare Zedek Medical Center, between 01.01.2016 and 31.12.2019. Patients were divided according to where they received care: general-ward, Intermediate-Care Unit, Intensive Care Unit (ICU), or both (Intermediate-Care and ICU). We examined the rates at which these different groups of patients received one or more of the following IMTs: mechanical ventilation, daytime bi-level positive airway pressure (BiPAP), or vasopressor therapy. Results: Most IMTs were delivered in a general-ward setting – ranging from 45.9% of IMT-treated hospitalizations involving combined mechanical ventilation and vasopressor therapy to as high as 87.4% of IMT-treated hospitalizations involving daytime BiPAP. Compared to ICU patients, Intermediate-Care Unit patients were older (mean age 75.1 vs 69.1, p < 0.001 for this and all other comparisons presented here), had longer hospitalizations (21.3 vs 14.5 days), and were more likely to die in-hospital (22% vs 12%). They were also more likely to receive most of the IMTs compared to ICU patients. For example, 9.7% of Intermediate-Care Unit patients received vasopressors, compared to 5.5% of ICU patients. Conclusion: In this study, most of the patients who received IMTs actually received them in a general-bed and not in a dedicated unit. These results imply that IMTs are predominantly delivered in unmonitored settings, and suggest an opportunity to re-examine where and how IMTs are given. In terms of health policy, these findings suggest a need to further examine the setting and patterns of intensive interventions, as well as a need to increase the number of beds dedicated to delivering intensive interventions. [ABSTRACT FROM AUTHOR]

Background: HIV assisted partner services (aPS) is an intervention to improve HIV status awareness among sex and drug-injecting partners of people newly diagnosed with HIV (index clients). Implementation fidelity—the degree to which an intervention is conducted as intended – is critical to effectiveness, but there are limited data about aPS fidelity when delivered by HIV testing service (HTS) providers. We explored factors affecting implementation fidelity to aPS in two high-HIV prevalence counties in western Kenya. Methods: We used convergent mixed methods adapting the conceptual framework for implementation fidelity within the aPS scale-up project. This was an implementation study examining scale-up of APS within HTS programs in Kisumu and Homa Bay counties that recruited male sex partners (MSPs) of female index clients. We defined implementation fidelity as the extent to which HTS providers followed the protocol for phone and in-person participant tracing at six expected tracing attempts. Quantitative data were collected from tracing reports in 31 facilities between November 2018 and December 2020, and in-depth interviews (IDIs) were conducted with HTS providers. Descriptive statistics were used to describe tracing attempts. IDIs were analyzed using thematic content analysis. Results: Overall, 3017 MSPs were mentioned of whom 98% (2969/3017) were traced, with most tracing attempts being successful (2831/2969, 95%). Fourteen HTS providers participated in the IDIs—mostly females (10/14, 71%) with a median age of 35 years (range 25–52), who all had post-secondary education (14/14, 100%). The proportion of tracing attempts occurring by phone ranged from 47 to 66%, with the highest proportion occurring on the first attempt and lowest on the sixth attempt. Contextual factors either enhanced or impeded implementation fidelity to aPS. Positive provider attitudes towards aPS and conducive work environment factors promoted implementation fidelity, while negative MSP responses and challenging tracing conditions impeded it. Conclusion: Interactions at the individual (provider), interpersonal (client—provider), and health systems (facility) levels affected implementation fidelity to aPS. As policymakers prioritize strategies to reduce new HIV infections, our findings highlight the importance of conducting fidelity assessments to better anticipate and mitigate the impact of contextual factors during the scale-up of interventions. [ABSTRACT FROM AUTHOR]

With more potent drug candidates being developed, the incidence of target‐mediated drug disposition (TMDD) in small‐molecule compounds has significantly increased in the past decade. Moreover, TMDD appears to apply to some small‐molecule compound classes. The main purpose of the current review is to increase the awareness of TMDD in a series of small‐molecule inhibitors of 11β‐hydroxysteroid dehydrogenase type 1 (HSD‐1) using ABT‐384, SPI‐62, MK‐0916, BMS‐823778, and BI‐187004 as case examples. Although developed independently by different pharmaceutical companies, these HSD‐1 inhibitors demonstrated strikingly similar nonlinear pharmacokinetic behaviors when wide dose ranges were evaluated in first‐in‐human (FIH) single ascending dose (SAD) and multiple ascending dose (MAD) studies. Recognizing TMDD in small‐molecule compounds is important, as the information can be leveraged to select the appropriate dose regimen, improve clinical trial design, as well as predict pharmacological target occupancy. In this review, we summarize the general pharmacokinetic features that facilitate the recognition of small‐molecule TMDD, provide case examples of specific HSD‐1 inhibitors, highlight the importance of recognizing TMDD of small‐molecule compounds during clinical development, and comment on the importance of utilizing pharmacometric modeling to facilitate the quantitative understanding of small‐molecule compounds exhibiting TMDD. [ABSTRACT FROM AUTHOR]

Rates of reported gonorrhea and chlamydial infections have increased substantially over the past decade in the USA and disparities persist across age and race/ethnicity. We aimed to understand potential changes in sexual behaviors, sexual network attributes, and sexually transmitted infection (STI) screening that may be contributing to these trends. We analyzed data from 29,423 female and 24,605 male respondents ages 15–44 years from the National Survey of Family Growth, 2008–2019. We used survey-weighted linear or logistic regression to evaluate linear temporal trends in sexual behaviors with opposite-sex partners, network attributes, and STI testing, treatment, and diagnosis. Significant declines were observed in condom use at last vaginal sex, mean number of vaginal sex acts, proportion of condom-protected sex acts in the past 4 weeks, and racial/ethnic homophily with current partners among males and females from 2008–2010 through 2017–2019. Among males, mean number of female partners in the past 12 months and concurrency also declined, while the percent reporting ever having sex with another male increased. Past-year testing for chlamydia and any STI increased among females. Research is needed to understand how these changes interact and potentially contribute to increasing reported gonorrhea and chlamydia diagnoses and identify avenues for future intervention. [ABSTRACT FROM AUTHOR]

The science of sports injury control and rehabilitation has traditionally focused on the analysis of biomechanical determinants of injury when energy exposure exceeds physiological threshold. This focused approach has made significant gains over the past 40 years to promote healthy and sustainable athletic participation and active living, yet injuries remain a significant problem due to the complex multifactorial nature of sports injuries. The public health scientific community has recognized the importance of biopsychosocioecological considerations for understanding disease and injury, and sports medicine research will fall behind if we do not follow the course of a complementary conceptual approach to enhance etiological understanding of athletic injury. Alongside the development of conventional scientific methodologies and analyses, progressing forward with a comprehensive, integrative holistic approach that acknowledges physical, mental, emotional, intellectual, social, and spiritual influences of the whole athlete is essential for progression to injury-free sports and active living. [ABSTRACT FROM AUTHOR]

Emergency department-based HIV self-testing (ED-HIVST) could increase HIV-testing services to high-risk, under-reached populations. This study sought to understand the injury patient acceptability of ED-HIVST. Injury patients presenting to the Kenyatta National Hospital Accident and Emergency Department were enrolled from March to May 2021. Likert item data on HIVST assessing domains of general acceptability, personal acceptability, and acceptability to distribute to social and/or sexual networks were collected. Ordinal regression was performed yielding adjusted odds ratios (aOR) to identify characteristics associated with high HIVST acceptability across domains. Of 600 participants, 88.7% were male, and the median age was 29. Half reported having primary care providers (PCPs) and 86.2% reported prior HIV testing. For each Likert item, an average of 63.5% of the participants reported they 'Agree Completely' with positive statements about ED-HIVST in general, for themselves, and for others. In adjusted analysis for general acceptability, those <25 (aOR = 1.67, 95%CI:1.36–2.08) and with prior HIV testing (aOR = 1.68, 95%CI:1.27–2.21) had greater odds of agreeing completely. For personal acceptability, those with a PCP (aOR = 3.31, 95%CI:2.72–4.03) and prior HIV testing (aOR = 1.83, 95%CI:1.41–2.38) had greater odds of agreeing completely. For distribution acceptability, participants with a PCP (aOR = 2.42, 95%CI:2.01–2.92) and prior HIV testing (aOR = 1.79, 95%CI: 1.38–2.33) had greater odds of agreeing completely. ED-HIVST is perceived as highly acceptable, and young people with prior testing and PCPs had significantly greater favourability. These data provide a foundation for ED-HIVST programme development in Kenya. [ABSTRACT FROM AUTHOR]

Objectives: The global distribution of human body proportions has long been attributed to thermoregulatory adaptation to climate. However, latitude has been the most common proxy for climate across ecogeographic studies. If thermoregulation was driving post‐cranial evolution, temperature should provide a better explanation for the morphological patterns observed than latitude, which encompasses temperature and other variables, as well as major events in human migration history. We investigate relationships between latitude, temperature, and postcranial form by distinguishing the strength of these potential selective factors from population structure. Materials & Methods: Quantitative genetic multivariate mixed models were used to estimate morphological effects associated with latitude, minimum temperature, and maximum temperature using osteometric data from 31 globally distributed groups, geographically matched genetic data from 54 groups, and geographically matched temperature data. Results: Dimensions reflecting body size (bi‐iliac breadth/femoral head size) show independent evolutionary responses from limb lengths. In models including population history, only dimensions reflecting body size show evidence of response to directional selection. Model results indicate that selection in response to minimum temperature has shaped evolution in body breadth and femoral head size. Models for limb length evolution accounting for population history match results of prior studies, but do not indicate responses to temperature‐driven directional selection. Conclusions: This study highlights the importance of considering multiple potential sources of selection within a multivariate evolutionary model, demonstrating the possible synergistic effects of selective pressures. These results complicate the classic thermoregulatory model of human postcranial evolution and show that factors other than temperature may have shaped post‐cranial evolution in humans. [ABSTRACT FROM AUTHOR]

Numerous per‐ and polyfluoroalkyl substances (PFAS) are of growing concern worldwide due to their ubiquitous presence, bioaccumulation and adverse effects. Surface waters in the United States have displayed elevated concentrations of PFAS, but so far discrete water sampling has been the commonly applied sampling approach. In the present study we field‐tested a novel integrative passive sampler, a microporous polyethylene tube, and derived sampling rates (Rs) for nine PFAS in surface waters. Three sampling campaigns were conducted, deploying polyethylene tube passive samplers in the effluent of two wastewater treatment plant (WWTP) effluents and across Narragansett Bay (Rhode Island, USA) for 1 month each in 2017 and 2018. Passive samplers exhibited linear uptake of PFAS in the WWTP effluents over 16–29 days, with in situ Rs for nine PFAS ranging from 10 ml day−1 (perfluoropentanoic acid) to 29 ml day−1 (perfluorooctanesulfonic acid). Similar sampling rates of 19 ± 4.8 ml day−1 were observed in estuarine field deployments. Applying these Rs values in a different WWTP effluent predicted dissolved PFAS concentrations mostly within 50% of their observations in daily composite water samples, except for perfluorobutanoic acid (where predictions from passive samplers were 3 times greater than measured values), perfluorononanoic acid (1.9 times), perfluorodecanoic acid (1.7 times), and perfluoropentanesulfonic acid (0.1 times). These results highlight the potential use of passive samplers as measurement and assessment tools of PFAS in dynamic aquatic environments. Environ Toxicol Chem 2022;41:2375–2385. © 2022 SETAC [ABSTRACT FROM AUTHOR]

Purpose of Review: We explored different behavioral economics (BE) mechanisms through which pre-exposure prophylaxis (PrEP) initiation and adherence could be impacted and examined recent work using BE principles to further HIV prevention efforts. We also generated new intervention ideas based on existing HIV testing and ART adherence literature. Recent Findings: There is limited work that uses BE principles to design interventions to increase PrEP initiation and adherence, mostly involving financial incentives. The recent works highlighted involve financial incentives and demonstrate that key populations are open to accepting monetary incentives to increase PrEP initiation and improve adherence. However, there are mixed results on the long-term impacts of using incentives to modify behavior. Summary: While there are a few ongoing studies that utilize BE principles to increase PrEP use, there is need to develop studies that test these concepts, to promote PrEP initiation and adherence. We suggest methods of exploring non-incentives-based ideas to increase PrEP use in key populations. [ABSTRACT FROM AUTHOR]

Brain and skull tissues interact through molecular signalling and mechanical forces during head development, leading to a strong correlation between the neurocranium and the external brain surface. Therefore, when brain tissue is unavailable, neurocranial endocasts are often used to approximate brain size and shape. Evolutionary changes in brain morphology may have resulted in secondary changes to neurocranial morphology, but the developmental and genetic processes underlying this relationship are not well understood. Using automated phenotyping methods, we quantified the genetic basis of endocast variation across large genetically varied populations of laboratory mice in two ways: (1) to determine the contributions of various genetic factors to neurocranial form and (2) to help clarify whether a neurocranial variation is based on genetic variation that primarily impacts bone development or on genetic variation that primarily impacts brain development, leading to secondary changes in bone morphology. Our results indicate that endocast size is highly heritable and is primarily determined by additive genetic factors. In addition, a non‐additive inbreeding effect led to founder strains with lower neurocranial size, but relatively large brains compared to skull size; suggesting stronger canalization of brain size and/or a general allometric effect. Within an outbred sample of mice, we identified a locus on mouse chromosome 1 that is significantly associated with variation in several positively correlated endocast size measures. Because the protein‐coding genes at this locus have been previously associated with brain development and not with bone development, we propose that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in neurocranial globularity. We identify a strain‐specific missense mutation within Akt3 that is a strong causal candidate for this genetic effect. Whilst it is not appropriate to generalize our hypothesis for this single locus to all other loci that also contribute to the complex trait of neurocranial skull morphology, our results further reveal the genetic basis of neurocranial variation and highlight the importance of the mechanical influence of brain growth in determining skull morphology. [ABSTRACT FROM AUTHOR]

One of the primary difficulties in treating patients with genetic syndromes is diagnosing their condition. Many syndromes are associated with characteristic facial features that can be imaged and utilized by computer-assisted diagnosis systems. In this work, we develop a novel 3D facial surface modeling approach with the objective of maximizing diagnostic model interpretability within a flexible deep learning framework. Therefore, an invertible normalizing flow architecture is introduced to enable both inferential and generative tasks in a unified and efficient manner. The proposed model can be used (1) to infer syndrome diagnosis and other demographic variables given a 3D facial surface scan and (2) to explain model inferences to non-technical users via multiple interpretability mechanisms. The model was trained and evaluated on more than 4700 facial surface scans from subjects with 47 different syndromes. For the challenging task of predicting syndrome diagnosis given a new 3D facial surface scan, age, and sex of a subject, the model achieves a competitive overall top-1 accuracy of 71%, and a mean sensitivity of 43% across all syndrome classes. We believe that invertible models such as the one presented in this work can achieve competitive inferential performance while greatly increasing model interpretability in the domain of medical diagnosis. [ABSTRACT FROM AUTHOR]

The impact of the adoption of desalination on relations between parties in transboundary settings is unclear. The previous literature has indicated that the effect of desalination on conflict and cooperation is an empirical matter. By reducing scarcity and variability, the adoption of desalination is likely to reduce the potential for conflict, though it may also create new conflicts, for instance, over water of marginal quality or over issues of equity. Its effect on cooperation is even more ambiguous, as it both offers parties more flexibility, which is likely to increase cooperation, but can be implemented unilaterally, which may reduce the need for cooperation. The little empirical work that has been published investigating these impacts has been largely based on anecdotal evidence or individual case studies. This paper presents a more systematic look at these impacts, using a mixed-method (quantitative and qualitative) analysis of interstate interactions before and after the adoption of large-scale seawater desalination. The results support the contention that while desalination has the potential to reduce conflict and increase cooperation, the impact of desalination on hydropolitics cannot be assumed a priori. Rather, it is largely context-dependent, and as such, it should not be viewed as a technological fix for transboundary water relations. [ABSTRACT FROM AUTHOR]

The solutions of a number of well-known boundary value problems of complex analysis (for example, the Riemann boundary value problem) can be found in the form of curvilinear integrals over the boundaries of domains under consideration. In this connection, the classical results on that problems concern domains with rectifiable boundaries only. On the other hand, the boundary value problems themselves make sense for non-rectifiable boundaries, too. This is the reason for recent development of theory of generalized integration over plane non-rectifiable Jordan curves and arcs. The existence of such generalized integrations over non-rectifiable arcs depends on certain geometry properties of the arcs in neighborhoods of their ends. Here we consider the connections of generalized integration and so-called torsions of the path of integration at its end points. [ABSTRACT FROM AUTHOR]

The Jordan River system is one of the most iconic and most contested river systems in the world. The once "mighty Jordan", which has served as the primary source of water for populations in several countries, is currently a severely denuded river system, with only a fraction of its historic flow. Several initiatives, however, aim to restore some of the basin's flows. This paper will provide a historical overview and analysis of the trajectory of the Jordan River system from being a primary supplier of water to a desiccated shadow of its former glory. It highlights the critical role international borders played in dividing control over the basin, resulting in different types and levels of water scarcity experienced by each of the basin's riparians, each of whom has implemented different strategies to cope with such scarcity. The paper then presents several plans for large-scale interbasin transfers involving desalinated water initiated by basin riparians in attempts to deal with water scarcity and highlights how these planned initiatives are set to transform the basin from a regional supplier of water to a net importer. [ABSTRACT FROM AUTHOR]