United States Department of Defense

Introduction Prescription stimulants are an effective FDA approved treatment for attention deficit hyperactivity disorder (ADHD) however their safety has come under scrutiny. Multiple studies demonstrate safe use in pediatric populations, but prescriptions are increasing to adults and it is not evident which comorbidities might place people at risk of adverse outcomes. The aim of this study is to identify risk factors of adverse cardiovascular events for individuals exposed to stimulants across the lifespan. Methods We conducted a case control study utilizing the TriNetX research network database. Individuals were included for study if they were younger than 90 years old and prescribed stimulants between January 1, 2010 and December 31, 2020. We utilized summary statistics, chi2, and multivariate logistic regression to identify risk factors for cardiovascular events. Results Of the 987,762 individuals prescribed stimulants, 49,902 experienced an adverse cardiovascular event. Individuals with atherosclerotic heart disease had the highest odds of adverse events (aOR = 36.7, p < .001). Hypertension (aOR = 2.78 p < .001), cocaine use (aOR = 1.64 p < .001), and anxiety (aOR = 1.46 p < .001) were also strongly predictive of adverse outcomes, but risk varied by age. Conclusions Atherosclerotic heart disease and its antecedents pose the greatest risk for cardiovascular events for people prescribed stimulants. Mental health diagnoses are also independent predictors and age may be an effect modifier of these relationships. ADHD was not an independent risk factor for major adverse cardiovascular events when controlling for other biopsychosocial variables in adult populations. Additional research focused on predictive models and prospective studies may be warranted to better inform clinical decisions regarding stimulant prescriptions for the broad demographic of patients that may benefit from these medications.

Deployments are stressful for both service members and their families. To promote the overall health and welfare of those impacted by military deployment, it is important to identify individual resilience-building resources that service members can employ to strengthen their own well-being, the well-being of their families, and the readiness of the force. This pilot study examines different resilience-building skills that may impact individual well-being, relationship quality, and family satisfaction post-deployment. A cross-sectional sample of 78 married U.S. military enlisted service members (n = 24) and commissioned officers (n = 54) completed the Coping Self-Efficacy Scale, Resilience Scale for Adults, Humor Styles Questionnaire, Mindful Attention Awareness Scale, Dispositional Resilience Scale, the emotional well-being and spirituality subscales of the Work-Life Well-Being Inventory, and the Social Problem-Solving Inventory-Revised. The use of a positive humor style was significantly associated with individual well-being. Spirituality and religious practices were significantly predictive of a service member’s family satisfaction. Responding to qualitative open-ended questions, service members identified their top 6 subcategories of stress, which were communication, moving, finances, family separation, children, and future employment during post-deployment. The strengths and resources reported as contributing the most to family effectiveness and well-being were personal character traits, external relationship skills, emotional maturity, and the ability to work. The results identified unique individual resilience-building resources for service members, which contribute to their well-being and the well-being of their families. Findings suggest that training on individual resilience-building resources for service members can offer support to the entire family system following military deployment.

During the past 25 years, vesicular stomatitis virus (VSV) has produced multiple outbreaks in the US, resulting in the emergence of different viral lineages. Currently, very little is known about the pathogenesis of many of these lineages, thus limiting our understanding of the potential biological factors favoring each lineage in these outbreaks. In this study, we aimed to determine the potential phenotypic differences between two VSV Indiana (VSIV) serotype epidemic strains using a pig model. These strains are representative of the epidemic lineages that affected the US between 1997 and 1998 (IN98COE) and between 2019 and 2020 (IN0919WYB2), the latter responsible for one of the most extensive outbreaks in the US. Our initial genome analysis revealed the existence of 121 distinct mutations between both strains, including the presence of a 14-nucleotide insertion in the intergenic region between the G and L genes observed in IN0919WYB2. The levels of viral RNA in clinical samples between pigs infected with IN98COE or IN0919WYB2 were compared. Overall, higher and prolonged expression of viral RNA in pigs infected with IN98COE was observed. However, clinically, IN0919WYB2 was slightly more virulent than IN98COE, as well as more efficient at producing infection through contact transmission. Additionally, infectious virus was recovered from more samples when the pigs were infected with IN0919WYB2, as revealed by virus isolation in cell culture, indicating the increased ability of this virus to replicate in pigs. Sequence analyses conducted from isolates recovered from both experimental groups showed that IN0919WYB2 produced more variability during the infection, denoting the potential of this strain to evolve rapidly after a single infection–contact transmission event in pigs. Collectively, the results showed that epidemic strains of VSIV may represent disparate phenotypes in terms of virulence/transmissibility for livestock, a situation that may impact the intensity of an epidemic outbreak. This study also highlights the relevance of pathogenesis studies in pigs to characterize phenotypic differences in VSV strains affecting livestock in the field.

Drucilla Cornell’s legacy defies easy summary. Thrown out of Stanford for protesting the Vietnam War, by the age of 20 she was organizing sweatshop workers for the United Auto Workers. Union organizing led her to law school (her only post-graduate degree is in law) and eventually a job as a law professor. Meanwhile, a defining encounter with Hegel at the age of 15 launched her intellectual trajectory, which would be followed by various schools of post-Hegelian thought (the Frankfurt School, Derridian deconstruction, Lacanian psychoanalysis, among others), feminisms both practical and theoretical, Rawlsian liberalism and, in her final work, African and Afro-Caribbean philosophy (I am leaving aside her plays and book on Clint Eastwood). Ecumenicism of this breadth can be a sign of shallow thinking. In her case, however, she had a sustained engagement with each tradition of thought, aimed at coaxing its essence from its native vocabulary in the faith that productive dialog is possible between radically different, and even opposed, intellectual traditions. In this reminiscence and memorial piece, I remember Drucilla as a teacher, mentor and friend.

For the first time, we describe phylogenomic signatures of an epidemic lineage of vesicular stomatitis Indiana virus (VSIV). We applied multiple evolutionary analyses to a dataset of 87 full-length genome sequences representing the circulation of an epidemic VSIV lineage in the US between 2019 and 2020. Based on phylogenetic analyses, we predicted the ancestral relationship of this lineage with a specific group of isolates circulating in the endemic zone of Chiapas, Mexico. Subsequently, our findings indicate that the lineage diversified into at least four different subpopulations during its circulation in the US. We identified single nucleotide polymorphisms (SNPs) that differentiate viral subpopulations and assessed their potential relevance using comparative phylogenetic methods, highlighting the preponderance of synonymous mutations during the differentiation of these populations. Purifying selection was the main evolutionary force favoring the conservation of this epidemic phenotype, with P and G genes as the main drivers of the evolution of this lineage. Our analyses identified multiple codon sites under positive selection and the association of these sites with specific functional domains at P, M, G, and L proteins. Based on ancestral reconstruction analyses, we showed the potential relevance of some of the sites identified under positive selection to the adaptation of the epidemic lineage at the population level. Finally, using a representative group of viruses from Colorado, we established a positive correlation between genetic and geographical distances, suggesting that positive selection on specific codon positions might have favored the adaptation of different subpopulations to circulation in specific geographical settings. Collectively, our study reveals the complex dynamics that accompany the evolution of an epidemic lineage of VSIV in nature. Our analytical framework provides a model for conducting future evolutionary analyses. The ultimate goal is to support the implementation of an early warning system for vesicular stomatitis virus in the US, enabling early detection of epidemic precursors from Mexico.

The US Department of Defense (DoD) is establishing its wastewater surveillance capacities to support national security objectives and promote the public health and medical readiness of US service members. Wastewater surveillance is an emerging technology that has traditionally been leveraged for detecting infectious diseases. However, its potential future applications could yield a vast and unpredictable amount of information that could be used for a wide variety of both health- and nonhealth-related purposes. The US military also serves an inimitable role for the country and its citizens, and exercises significant levels of control over its service members compared to civilian organizations. Further, its present and potential wastewater surveillance activities may reach far beyond just military installations. These factors raise unique ethical considerations that must be accounted for by leaders and policymakers to ensure the DoD implements a wastewater surveillance network in a manner that is both impactful in supporting public health and appropriate to the scope and population under surveillance. This paper explores important ethical features in conducting wastewater surveillance that are both specific to the DoD experience and applicable to wider public health initiatives.

Japanese encephalitis virus (JEV) is associated with encephalitis in humans and reproductive and neurological illness in pigs. JEV has expanded beyond its native distribution in southeast Asia, with identifications in Europe (2010) and Africa (2016), and most recently, its spread into mainland Australia (2021−2022). The introduction of JEV into the United States (US) is a public health risk, and could also impact animal health and the food supply. To efficiently and cost-effectively manage risk, a better understanding of how and where diseases will be introduced, transmitted, and spread is required. To achieve this objective, we updated our group's previous qualitative risk assessment using an established semi-quantitative risk assessment tool (MINTRISK) to compare the overall rate of introduction and risk, including impacts, of JEV in seven US regions. The rate of introduction from the current region of distribution was considered negligible for the Northeast, Midwest, Rocky Mountain, West, Alaska, and Hawaii regions. The South region was the only region with a pathway that had a non-negligible rate of introduction; infected mosquito eggs and larvae introduced via imported used tires (very low; 95% uncertainty interval (UI) = negligible to high). The overall risk estimate for the South was very high (95% UI = very low to very high). Based on this risk assessment, the South region should be prioritized for surveillance activities to ensure the early detection of JEV. The assumptions used in this risk assessment, due to the lack of information about the global movement of mosquitoes, number of feral pigs in the US, the role of non-ardeid wild birds in transmission, and the magnitude of the basic reproduction ratio of JEV in a novel region, need to be fully considered as these impact the estimated probability of establishment.

Synthetic aperture radar (SAR) utilizes an aircraft-carried antenna to emit electromagnetic pulses and detect the returning echoes. As the aircraft travels across a designated area, it synthesizes a large virtual aperture to improve image resolution. Inspired by SAR, we introduce synthetic aperture ptycho-endoscopy (SAPE) for micro-endoscopic imaging beyond the diffraction limit. SAPE operates by hand-holding a lensless fiber bundle tip to record coherent diffraction patterns from specimens. The fiber cores at the distal tip modulate the diffracted wavefield within a confined area, emulating the role of the ‘airborne antenna’ in SAR. The handheld operation introduces positional shifts to the tip, analogous to the aircraft’s movement. These shifts facilitate the acquisition of a ptychogram and synthesize a large virtual aperture extending beyond the bundle’s physical limit. We mitigate the influences of hand motion and fiber bending through a low-rank spatiotemporal decomposition of the bundle’s modulation profile. Our tests demonstrate the ability to resolve a 548-nm linewidth on a resolution target. The achieved space-bandwidth product is ~1.1 million effective pixels, representing a 36-fold increase compared to that of the original fiber bundle. Furthermore, SAPE’s refocusing capability enables imaging over an extended depth of field exceeding 2 cm. The aperture synthesizing process in SAPE surpasses the diffraction limit set by the probe’s maximum collection angle, opening new opportunities for both fiber-based and distal-chip endoscopy in applications such as medical diagnostics and industrial inspection.

HIV-1 is characterized by remarkable genetic diversity resulting from its high replication rate, error-prone reverse transcriptase enzyme and recombination events. In Uganda, HIV-1 subtype diversity is mostly dominated by subtypes A, D, and A1/D Unique Recombinant Forms (URFs). In this study, deep sequences of HIV from patients with known antiretroviral therapy (ART) status were analyzed to determine the subtypes and to identify drug-resistance mutations circulating in the study population. Of the 187 participant samples processed for next-generation sequencing (NGS), 137 (73%) were successfully classified. The majority of HIV-1 strains were classified as subtype A (75, 55%), D (43, 31%), with other subtypes including C (3, 2%), A1/D (9, 7%) and CRF10_CD (1, <1%). Recombinant analysis of nine complete A1/D HIV genomes identified novel recombination patterns described herein. Furthermore, we report for the first time in Uganda, an HIV-1 CRF10_CD strain from a fisherfolk in a Lake Victoria Island fishing community.

Background In 2019, WHO recommended dolutegravir (DTG) as a backbone for first- and second-line antiretroviral therapy (ART) regimens for people living with HIV (PLHIV). According to the 2018 Uganda’s HIV treatment guidelines, patients with viral non-suppression (≥1,000 copies/mL) should receive intensive adherence counseling (IAC) with repeat viral load (VL) within 6 months. This analysis focused on the prevalence and factors associated with viral suppression following IAC among PLHIV on DTG-based regimens (DBRs) with an initial episode of viral non-suppression (VNS) in Uganda. Methods We conducted a retrospective analysis for PLHIV on DBRs with an initial episode of VNS (≥1,000 copies/mL) in Uganda during October 2019–September 2020 who had a follow up VL test result during September 2020–July 2021. Data were abstracted from the Central Public Health Laboratory (CPHL) database, including patient demographics and VL results. Viral non-suppression (VNS) was defined as a VL test result of ≥1,000 copies/mL. We characterized PLHIV on DBRs and used logistic regression models to determine factors associated with VL suppression after an initial episode of VNS. Results A total of 564 PLHIV on DBRs with an initial episode of VNS were followed up and 43 were excluded due to missing data. Of the 521, 220 (42.2%) were children (<15 years) and 231 (44.3%) were female. Median age was 28 years (interquartile range [IQR]: 12–43 years), and median duration on DBRs was 12 months (IQR: 6–15 months). Overall, 80.8% (421/521) PLHIV had a suppressed viral load at first follow up testing (children = 74.5% [164/220]; adults = 85.4% [257/301]). Children with initial VL results ≥5,000 copies/mL were less likely to achieve viral suppression at follow up testing compared to those with <5,000 copies/mL (AOR: 0.38; 95% CI: 0.20–0.71; p = 0.002). Conclusions In a programmatic setting, most adults and children suppressed following an initial episode of VNS on DBRs. High rates of suppression after VNS suggest adherence challenges, rather than drug resistance. Continuation of DBRs should be considered before regimen switch.

When do non-international armed conflicts (NIACs) end? Determining the existence of a NIAC requires a detailed, fact-intensive inquiry. Since the International Criminal Tribunal for the Former Yugoslavia's seminal decision in the Tadić case, international courts and tribunals have evaluated the existence of NIACs under the Tadić test's two-pronged inquiry into intensity and organization. Although that decision also pronounced that international humanitarian law (IHL) continues to apply until a “peaceful settlement is achieved,” neither international tribunals nor scholars have articulated a comparably widely accepted and well-developed test for determining the end of NIACs. At the same time – and especially since 9/11 – States have increasingly relied on IHL to meet the threat posed by non-State actors, broadening the scope of conflict-related liabilities in armed conflict without conferring the privileges or immunities otherwise inherent in IHL. This one-sided approach twists the purpose of IHL and places members of organized armed groups into legal black holes without temporal limitations, as States resist the termination of “armed conflict” irrespective of the continuing intensity of violence or the level of organization of non-State actors. Ultimately, the current approach gives States broad discretion without appropriate safeguards, which undermines the proper application of human rights and humanitarian principles within conflict and prevents the establishment of a sustainable peace. This paper argues that the most appropriate test for ascertaining the end of a NIAC is one that combines objective consideration of the diminution of organized and intense hostilities below the Tadić threshold with the likelihood that hostilities will not again rise above that threshold. It thus draws from but does not fully endorse the preferred approach of the International Committee of the Red Cross (ICRC), which focuses on the lasting termination of hostilities, ¹ while abjuring a general temporal limitation. Although commendable for its effort to avoid the legal uncertainty that attends the revolving conflict classification problem, the ICRC's approach unfortunately tends to encode existing uncertainty surrounding the termination of NIACs and to indistinctly prolong the application of IHL to erstwhile conflict situations. In contrast, the authors suggest that a test for the end of NIAC based on a specific period (five months following the diminution of organized and intense hostilities below the Tadić threshold), subject to an evaluation of the risk that those hostilities may resume, better balances certainty of legal application with the promotion of a return to peace. The authors will employ the facts of diverse case studies, including the FARC in Colombia, the LTTE in Sri Lanka, numerous armed groups in Mali, and the United States with Al-Qaeda, to build a legal standard that courts can use to determine IHL's continuing applicability to an erstwhile armed conflict.

Detection canines serve critical roles to support the military, homeland security and border protection. Some explosive detection tasks are physically demanding for dogs, and prior research suggests this can lead to a reduction in olfactory detection sensitivity. To further evaluate the effect of exercise intensity on olfactory sensitivity, we developed a novel olfactory paradigm that allowed us to measure olfactory detection thresholds while dogs exercised on a treadmill at two different exercise intensities. Dogs (n = 3) showed a decrement in olfactory detection for 1-bromooctane at 10-3 (v/v) dilutions and lower under greater exercise intensity. Dogs' hit rate for the lowest concentration dropped from 0.87 ± 0.04 when walking at low intensity to below 0.45 ± 0.06 when trotting at moderate intensity. This decline had an interaction with the duration of the session in moderate intensity exercise, whereby dogs performed near 100% detection in the first 10 min of the 8 km/h session, but showed 0% detection after 20 min. Hit rates for high odor concentrations (10-2) were relatively stable at both low (1 ± 0.00) and moderate (0.91 ± 0.04) exercise intensities. The paradigm and apparatus developed here may be useful to help further understand causes of operationally relevant olfactory detection threshold decline in dogs.

Metallic microlattice (MML) materials enable novel material properties through geometry and topology, and through additive manufacturing (AM) there exists a viable and scalable method of producing the fine networks of struts and nodes which make up an architected lattice. However, AM methods often induce locally high cooling rates, which lead to residual strains and anisotropic microstructures which can limit how tunable and predictable the properties of a lattice will be across its volume. Residual strains can degrade mechanical properties or act as strain concentrators and contribute to the failure dynamics of a lattice under load. In the micron scale regime of lattices this means the microstructure is the point of failure minimization, and we show that the orientation of a strut between two edge cases within a lattice and its proximity to a heatsink will change the strain distribution and microstructure within a lattice strut depending on the manufacturing technology used. We show that changes in energy density and solidification conditions between two AM methods, laser and electron beam powder bed fusion (PBF-LB and PBF-EB) lead to different magnitudes of residual strain and anisotropy, with PBF-EB showing far lower levels of residual strain and greater consistency in both strain and microstructure invariant of strut orientation next to a heatsink.

Objective To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25–49 years in Uganda, and to analyse the programme data. Methods The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

In this paper we explore the role of matrix scaling on a matrix of counts when building a topic model using non-negative matrix factorization. We present a scaling inspired by the normalized Laplacian (NL) for graphs that can greatly improve the quality of a non-negative matrix factorization. The results parallel those in the spectral graph clustering work of [12], where the authors proved adjacency spectral embedding (ASE) spectral clustering was more likely to discover core-periphery partitions and Laplacian Spectral Embedding (LSE) was more likely to discover affinity partitions. In text analysis non-negative matrix factorization (NMF) is typically used on a matrix of co-occurrence “contexts” and “terms” counts. The matrix scaling inspired by LSE gives significant improvement for text topic models in a variety of datasets. We illustrate how matrix scalings in NMF can dramatically improve the quality of a topic model on three datasets where human annotation is available. Using the adjusted Rand index (ARI), a measure cluster similarity we see an increase of 50% for Twitter data and over 200% for a newsgroup dataset versus using counts, which is the analogue of ASE. For clean data, such as those from the Document Understanding Conference, NL gives over 40% improvement over ASE. We conclude with some analysis of this phenomenon and some connections of this scaling with other matrix scaling methods.