Game-theoretic algorithm for interdependent infrastructure network restoration in a decentralized environment.

Having reliable interdependent infrastructure networks is vital for well-being of a safe and productive society. Systems are vulnerable to failure or performance loss due to their interdependence among various networks, as each failure can propagate through the whole system. Although the conventional view has concentrated on optimizing the restoration of critical interdependent infrastructure networks using a centralized approach, having a lone actor as a decision-maker in the system is substantially different from the actual restoration decision environment, wherein infrastructure utilities make their own decisions about how to restore their network service. In a decentralized environment, the definition of whole system optimality does not apply as each decision-maker's interest may not converge with the others. Subsequently, this results in each decision-maker developing its own reward functions. Therefore, in this study, we address the concern of having multiple decision-makers with various payoff functions in interdependent networks by proposing a decentralized game theory algorithm for finding Nash equilibria solutions for network restoration in postdisaster situations.

Human Immunodeficiency Virus (HIV) Care Continuum Outcomes After Transition to Adult Care Among a Prospective Cohort of Youth With HIV in Atlanta, Georgia.

BACKGROUND: Healthcare transition from pediatric to adult-oriented clinical settings is often viewed as a high-risk time for care disengagement. However, there is a paucity of prospective, longitudinal research documenting human immunodeficiency virus (HIV) care outcomes after healthcare transition. METHODS: We conducted a prospective, observational cohort study of healthcare transition among youth enrolled at an HIV care center in Atlanta, Georgia. Pediatric clinic patients (average age, 24 years) were enrolled up to 3 months before the expected transition and were followed up to determine linkage, retention, and viral suppression in adult care through electronic medical record abstractions at the baseline and at 6, 12, 18, and 24 months. RESULTS: The majority of our cohort (n = 70) was male (88.6%) and black (92.9%) and acquired HIV horizontally (80%). Most of our cohort was linked to adult care by 12 months (84%) after enrollment. Of those who linked to adult care by 12 months, retention rates were 86% (95% confidence interval, 78%-94%) at 6 months, 76% (66%-86%) at 12 months, and 66% (55%-78%) at 18 and 24 months. Once in adult care, the proportion with viral suppression was stable (73% at baseline and 74%, 77%, 67%, and 78% at 6, 12, 18, and 24 months, respectively). CONCLUSIONS: Although most youth successfully linked to adult care, retention rates decreased over the 24-month follow-up period. Rates of viral suppression were stable for those who remained in care. Strategies to support retention in adult care will be critical to optimizing this transition for youth with HIV.

Changing the Reaction Pathway of Silyl-Prins Cyclization by Switching the Lewis Acid: Application to the Synthesis of an Antinociceptive Compound.

Developing new procedures for the synthesis of tetrahydropyrans in a very stereoselective manner is of great importance for the synthesis of THP-containing natural products. Here, we report an interesting protocol for the synthesis of polysubstituted halogenated tetrahydropyrans by silyl-Prins cyclization of vinylsilyl alcohols, in which the nature of the Lewis acid determines the outcome of the process. The methodology has been applied to the synthesis of a known antinociceptive.

HIV in youth prevention in the emergency department initiative: A survey of pediatric emergency medicine providers.

BACKGROUND: The incidence of HIV among adolescents remains high, and adolescents are known to participate in sexual behaviors that increase their risk for HIV, such as unprotected sex and sex with multiple partners. HIV pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing HIV when taken daily and is approved by the FDA for use in adolescents. Efforts to screen patients in adult emergency departments and connect them with PrEP services have been validated. We surveyed pediatric emergency medicine (PEM) providers to determine their knowledge of PrEP, prescribing practices, willingness to prescribe, and barriers to a screening protocol in the pediatric emergency department (PED). METHODS: We administered a survey to a multidisciplinary group of PEM providers to measure knowledge, use, willingness, and implementation barriers to PrEP as well as elements needed for a successful referral system. RESULTS: A total of 87 responses were included for analysis. While 79.1% of all providers had heard of PrEP, only 14.8% of prescribing providers had ever discussed PrEP with a patient, and none had ever prescribed PrEP. Overall, 76.3% of all providers were knowledgeable about PrEP based on answers to true/false questions, with prescribing providers significantly more likely to be knowledgeable compared to nurses (p = 0.005). Knowledgeable providers had higher willingness scores to refer for PrEP compared to providers who were not knowledgeable. Ninety-two percent of providers felt a PrEP referral process from the PED would be feasible. Creation of an eligibility algorithm and educational materials were the most common efforts providers preferred to make them more likely to refer for PrEP. The most notable barriers perceived by providers included patient noncompliance with therapy (20.9%), acceptance of PrEP discussion among patients and parents (19.8%), and cost of therapy (15.1%). CONCLUSION: PEM providers are knowledgeable about PrEP but have little experience with discussing or prescribing PrEP. Their willingness to refer for PrEP and anticipated feasibility of a PrEP referral system is encouraging. These results support the need for future educational efforts among PEM providers and creation of referral systems for PrEP services from the PED.

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs.

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.

Multiregional, multi-industry impacts of fairness on pandemic policies.

The health and economic crisis caused by the COVID-19 pandemic highlights the necessity for a deeper understanding and investigation of state- and industry-level mitigation policies. While different control strategies in the early stages, such as lockdowns and school and business closures, have helped decrease the number of infections, these strategies have had an adverse economic impact on businesses and some controversial impacts on social justice. Therefore, optimal timing and scale of closure and reopening strategies are required to prevent both different waves of the pandemic and the negative socioeconomic impact of control strategies. This article proposes a novel multiobjective mixed-integer linear programming formulation, which results in the optimal timing of closure and reopening of states and industries in each. The three objectives being pursued include: (i) the epidemiological impact of the pandemic in terms of the percentage of the infected population; (ii) the social vulnerability index of the pandemic policy based on the vulnerability of communities to getting infected, and for losing their job; and (iii) the economic impact of the pandemic based on the inoperability of industries in each state. The proposed model is implemented on a dataset that includes 50 states, the District of Columbia, and 19 industries in the United States. The Pareto-optimal solutions suggest that for any control decision (state and industry closure or reopening), the economic impact and the epidemiological impact change in the opposite direction.

Factors Associated With Anal High-Grade Intraepithelial Lesions and Carcinoma Among Young Men Who Have Sex With Men and Transgender Women With HIV in Atlanta.

OBJECTIVE: This study aimed to evaluate factors associated with anal high-grade intraepithelial lesions (HSIL) and anal carcinoma among young men who have sex with men (MSM) and transgender women (TW) with HIV in Atlanta, GA, to better inform screening guidelines and preventative measures. MATERIALS AND METHODS: Cross-sectional retrospective chart review was completed for cisgender MSM and TW with HIV aged 13-25 years at the Grady Ponce and Family Youth Clinic in Atlanta, GA, from 2009 to 2020. High-grade anal disease was defined as anal intraepithelial neoplasia (AIN) 2, 3, or anal carcinoma (AIN 2+). Associations between clinical and demographic factors with AIN 2+ were estimated using logistic regression. Adjusted odds ratios (aORs) and associated 90% CIs are reported. RESULTS: One hundred nine MSM and TW with HIV who underwent anoscopy were included. One hundred three participants received anal biopsies, and 62% had AIN 2+. Being incompletely or unvaccinated against human papillomavirus (HPV, 0-2 doses) relative to being fully vaccinated (3 doses; aOR = 5.85; 90% CI = 1.28-26.83; p = .06) and having ever received surgical treatment for anogenital HPV (aOR = 2.89; 90% CI = 1.10-7.65; p = .07) were associated with AIN 2+, controlling for age and CD4 T-cell count at time of biopsy. CONCLUSIONS: Our study found a high prevalence of anal HSIL among young MSM and TW with HIV. Those who had ever received surgical treatment for anogenital HPV and those who were incompletely or unvaccinated against HPV were more likely to have HSIL. Our data emphasize the urgent need to improve HPV vaccination efforts and to pursue larger surveillance studies of anal HSIL and carcinoma among young MSM and TW with HIV.

Modeling social, economic, and health perspectives for optimal pandemic policy decision-making.

While different control strategies in the early stages of the COVID-19 pandemic have helped decrease the number of infections, these strategies have had an adverse economic impact on businesses. Therefore, optimal timing and scale of closure and reopening strategies are required to prevent both different waves of the pandemic and the negative economic impact of control strategies. This paper proposes a novel multi-objective mixed-integer linear programming (MOMILP) formulation, which results in the optimal timing of closure and reopening of states and industries in each state to mitigate the economic and epidemiological impact of a pandemic. The three objectives being pursued include: (i) the epidemiological impact, (ii) the economic impact on the local businesses, and (iii) the economic impact on the trades between industries. The proposed model is implemented on a dataset that includes 11 states, the District of Columbia, and 19 industries in the US. The solved by augmented ε-constraint approach is used to solve the multi-objective model, and a final strategy is selected from the set of Pareto-optimal solutions based on the least cubic distance of the solution from the optimal value of each objective. The Pareto-optimal solutions suggest that for any control decision (state and industry closure or reopening), the economic impact and the epidemiological impact change in the opposite direction, and it is more effective to close most states while keeping the majority of industries open during the planning horizon.

Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders.

OBJECTIVE: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a sample of neurological patients. METHODS: This prospective study with consecutive sampling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. RESULTS: A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti-N-methyl-d-aspartate receptor [NMDAR]) was confirmed. CONCLUSIONS: Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.

Photostability of 2,6-diaminopurine and its 2'-deoxyriboside investigated by femtosecond transient absorption spectroscopy.

Ultraviolet radiation (UVR) from the sun is essential for the prebiotic syntheses of nucleotides, but it can also induce photolesions such as the cyclobutane pyrimidine dimers (CPDs) to RNA or DNA oligonucleotide in prebiotic Earth. 2,6-Diaminopurine (26DAP) has been proposed to repair CPDs in high yield under prebiotic conditions and be a key component in enhancing the photostability of higher-order prebiotic DNA structures. However, its electronic relaxation pathways have not been studied, which is necessary to know whether 26DAP could have survived the intense UV fluxes of the prebiotic Earth. We investigate the electronic relaxation mechanism of both 26DAP and its 2'-deoxyribonucleoside (26DAP-d) in aqueous solution using steady-state and femtosecond transient absorption measurements that are complemented with electronic-structure calculations. The results demonstrate that both purine derivatives are significantly photostable to UVR. It is shown that upon excitation at 287 nm, the lowest energy 1ππ* state is initially populated. The population then branches following two relaxation coordinates in the 1ππ* potential energy surface, which are identified as the C2- and C6-relaxation coordinates. The population following the C6-coordinate internally converts to the ground state nonradiatively through a nearly barrierless conical intersection within 0.7 ps in 26DAP or within 1.1 ps in 26DAP-d. The population that follows the C2-relaxation coordinate decays back to the ground state by a combination of nonradiative internal conversion via a conical intersection and fluorescence emission from the 1ππ* minimum in 43 ps and 1.8 ns for the N9 and N7 tautomers of 26DAP, respectively, or in 70 ps for 26DAP-d. Fluorescence quantum yields of 0.037 and 0.008 are determined for 26DAP and 26DAP-d, respectively. Collectively, it is demonstrated that most of the excited state population in 26DAP and 26DAP-d decays back to the ground state via both nonradiative and radiative relaxation pathways. This result lends support to the idea that 26DAP could have accumulated in large enough quantities during the prebiotic era to participate in the formation of prebiotic RNA or DNA oligomers and act as a key component in the protection of the prebiotic genetic alphabet.

Feasibility and acceptability of B6: a social capital program for young Black gay, bisexual and other men who have sex with men living with HIV.

Young Black gay, bisexual and other men who have sex with men (YB-GBMSM) are disproportionately burdened by HIV and often exhibit suboptimal engagement in HIV care. With the goal of increasing engagement in HIV care, we designed a culturally specific, theory-based group-level program, Brothers Building Brothers by Breaking Barriers (B6), which aimed to strengthen resilience and social capital among YB-GBMSM living with HIV. We conducted a pilot trial to evaluate the program's acceptability and feasibility. Through clinic-based recruitment and community outreach events, we recruited and enrolled 71 YB-GBMSM into the study. Participants were randomized to either the B6 program or a control comparison program. Post-session evaluation surveys and in-depth qualitative interviews showed B6 to have high levels of acceptability and satisfaction. Specifically, participants described benefits to interacting in a group with other YB-GBMSM, and several described increased comfort with their own gay identities after participation. No adverse events or safety concerns were reported. However, there were challenges to feasibility, as reflected in recruitment and retention rates. The B6 program was highly acceptable among YB-GBMSM living with HIV; however, innovative program delivery methods and implementation strategies will be needed to improve recruitment and retention in future implementation of B6.

The Tetrahydrofuran Motif in Polyketide Marine Drugs.

Oxygen heterocycles are units that are abundant in a great number of marine natural products. Among them, marine polyketides containing tetrahydrofuran rings have attracted great attention within the scientific community due to their challenging structures and promising biological activities. An overview of the most important marine tetrahydrofuran polyketides, with a focused discussion on their isolation, structure determination, approaches to their total synthesis, and biological studies is provided.

The Tetrahydrofuran Motif in Marine Lipids and Terpenes.

Heterocycles are particularly common moieties within marine natural products. Specifically, tetrahydrofuranyl rings are present in a variety of compounds which present complex structures and interesting biological activities. Focusing on terpenoids, a high number of tetrahydrofuran-containing metabolites have been isolated during the last decades. They show promising biological activities, making them potential leads for novel antibiotics, antikinetoplastid drugs, amoebicidal substances, or anticancer drugs. Thus, they have attracted the attention of the synthetics community and numerous approaches to their total syntheses have appeared. Here, we offer the reader an overview of marine-derived terpenoids and related compounds, their isolation, structure determination, and a special focus on their total syntheses and biological profiles.

Understanding social capital among young black gay and bisexual men living with HIV: a qualitative exploration.

Social capital, defined as the sum of an individual's resource-containing, reciprocal and trustworthy social network connections, has been associated with improved engagement in care among people living with HIV globally. We conducted a qualitative interview study of social capital among 28 young Black gay, bisexual and other men who have sex with men ages 18-29 living with HIV in Atlanta, Georgia. We asked participants about bonding capital (relationships between individuals with similar demographic characteristics), bridging capital (relationships with individuals of different backgrounds), collective efficacy (involvement with community organisations) and satisfaction with their social networks. We found that participants described bonding capital from friends and family in depth, while more gaps were noted in bridging capital and collective efficacy. Bonding capital derived from families was especially critical to participants' satisfaction with their social capital. Findings suggest that interventions targeting young Black gay, bisexual and other men who have sex with men should build upon strong bonds with family and friends, and/or fill gaps in bridging capital and collective efficacy by connecting young men to mentors and organisations.

Comparison of Targeted and Routine Adolescent HIV Screening in a Pediatric Emergency Department.

OBJECTIVES: The aims of the study were (1) to compare targeted and routine HIV screening in a pediatric emergency department (PED) and (2) to compare provider documented HIV risk assessment with adolescent perception of HIV risk assessment conducted during the PED visit. METHODS: This prospective study ran concurrent to a PED routine HIV screening pilot. Adolescents could be tested for HIV by the PED provider per usual care (targeted testing); if not tested, they were approached for the routine screening pilot. A subset of adolescents completed a questionnaire on HIV risk. χ 2 analysis compared adolescents with targeted testing and routine screening. HIV-tested patients were asked if HIV risk was assessed; κ analysis compared this with documentation in the provider note. RESULTS: Over 4 months, 107 adolescents received targeted testing and 344 received routine screening. One 14-year-old patient tested positive by routine screening; this adolescent had 2 PED visits without targeted testing within 60 days. Compared with routine screening, adolescents with targeted testing were more likely female (82% vs 57%, P < 0.001), 16 years or older (71% vs 44%, P < 0.001), or had genitourinary/gynecologic concerns (48% vs 6%, P < 0.001). Adolescents with HIV risk factors were missed by targeted testing but received routine screening. Adolescents with documented HIV risk assessment were more likely to receive targeted testing. There was moderate agreement (κ = 0.61) between provider documentation and adolescent perception of HIV risk assessment. CONCLUSIONS: There are gaps in PED HIV risk assessment and testing, which may miss opportunities to diagnose adolescent HIV. Routine HIV screening addresses these gaps and expands adolescent HIV testing in the PED.

Acute Toxicity of Daphnia magna Neonates Exposed to Single and Composite Mixtures of Four Emerging Contaminants.

The effects of emerging contaminants on environmental health are of high concern, especially those potentially induced by mixtures. We assessed single and composite mixtures of triclosan (T), 17ß-estradiol (E2), sulfamethoxazole (SMX), and nicotine (N) at various concentrations, on neonates of Daphnia magna. When used in single exposure, T and N induced high toxicity (100% immobility, each one), compared to SMX and E2 (2.5% and 10% immobility, respectively). When T, E2, SMX and N were in mixture, T had the highest contribution to the overall toxicity in mixture exposures. The N toxicity lowered when in a fourfold exposure (85% immobility in fourfold exposure). Due to the high toxicity of T and N, both alone and in the mixtures, our results can serve as a warning about the use of these substances and their release in the aquatic ecosystem.

Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide in Pediatric Hemophagocytic Lymphohistiocytosis.

PURPOSE: Primary hemophagocytic lymphohistiocytosis is a severe and uncommon disease affecting pediatric patients. Genetic abnormalities have been related to altered apoptosis and exaggerated inflammatory reactions. Chemoimmunotherapy and stem cell transplantation are treatment options, but transplant is the only curative treatment. Here we aim to describe the treatment with hematopoietic stem cell transplantation with a novel strategy and the outcomes. METHODS: An observational, descriptive, case series study was performed in pediatric patients of two high complexity medical centers in Colombia. Data was collected retrospectively between 2015 and 2020. RESULTS: We describe five pediatric cases with a diagnosis of primary hemophagocytic lymphohistiocytosis. All were treated with replete-cell haploidentical hematopoietic stem transplantation, reduced-intensity conditioning, and post-transplant cyclophosphamide, in two high-complexity centers in Colombia. All patients are alive, and one is receiving management for chronic graft-versus-host disease. CONCLUSION: To the best of our knowledge, there are few reports in the literature with this strategy, promising a possible alternative when there are no other donor options.

Dissociable Neural Information Dynamics of Perceptual Integration and Differentiation during Bistable Perception.

At any given moment, we experience a perceptual scene as a single whole and yet we may distinguish a variety of objects within it. This phenomenon instantiates two properties of conscious perception: integration and differentiation. Integration is the property of experiencing a collection of objects as a unitary percept and differentiation is the property of experiencing these objects as distinct from each other. Here, we evaluated the neural information dynamics underlying integration and differentiation of perceptual contents during bistable perception. Participants listened to a sequence of tones (auditory bistable stimuli) experienced either as a single stream (perceptual integration) or as two parallel streams (perceptual differentiation) of sounds. We computed neurophysiological indices of information integration and information differentiation with electroencephalographic and intracranial recordings. When perceptual alternations were endogenously driven, the integrated percept was associated with an increase in neural information integration and a decrease in neural differentiation across frontoparietal regions, whereas the opposite pattern was observed for the differentiated percept. However, when perception was exogenously driven by a change in the sound stream (no bistability), neural oscillatory power distinguished between percepts but information measures did not. We demonstrate that perceptual integration and differentiation can be mapped to theoretically motivated neural information signatures, suggesting a direct relationship between phenomenology and neurophysiology.

Bacillus as a source of phytohormones for use in agriculture.

Microbial plant biostimulants (MPBs) are capable of improving the productivity and quality of crops by activating plant physiological and molecular processes, representing an efficient tool in sustainable agriculture. Through phytohormone production, MPBs are capable of regulating plant physiological processes, increasing the productivity and quality of crops, in addition to being an efficient alternative in the industrial production of phytohormones. Bacillus is a bacterial genus with various species on the market being used as biopesticides, due to their ability to produce antimicrobial, nematicidal and insecticidal compounds. The capability of Bacillus species to protect plants against pests and/or pathogens also entails the triggering or increase of plant defense responses. Furthermore, a relevant number of species from the genus Bacillus provoke plant growth promotion by different mechanisms such as increasing the tolerance of their host plants under abiotic stress conditions or improving plant nutrition. In several cases, the plant response is mediated by the bacterial production of phytohormones. In the present work, all studies from recent decades where the production of phytohormones by Bacillus species are reported, highlighting their role in host plants and the mechanisms by which they are capable of increasing plant growth, promoting their development, and improving their response to different stresses. KEY POINTS: • Different Bacillus-species are known as agricultural biopesticides. • Bacillus role as biostimulants is being increasingly addressed. • Bacillus represents a good source of phytohormones of agricultural interest.

Efficacy of Aflibercept Treatment and Its Effect on the Retinal Perfusion in the Oxygen-Induced Retinopathy Mouse Model of Retinopathy of Prematurity.

INTRODUCTION: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. OBJECTIVE: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. METHODS: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. RESULTS: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. CONCLUSIONS: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.