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In this paper, we apply the Analytic Hierarchy Process approach to conflict resolution in the context of the Russia-Ukraine conflict. We build models that illustrate the evaluation criteria, strategic and sub-criteria, and concessions for each party in this negotiation. Ratings are used to evaluate the degree to which concessions contribute or take away from successful resolution of the conflict. Afterwards, gain ratios are built to determine the benefit-cost scores so that concessions may be traded that result in equitable solutions. The approach presented here demonstrates for the first time why all concessions that parties to a conflict may offer might not trade all at once. A Max-Min optimization approach is used to maximize the gain to both parties of the conflict while minimizing the disparity in gain between the two.
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Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.
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Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/farmacología , Síndrome Metabólico/tratamiento farmacológico , Absorción/efectos de los fármacos , Administración Oral , Fosfatasa Alcalina/administración & dosificación , Fosfatasa Alcalina/genética , Animales , Compuestos Azo , Línea Celular , Cartilla de ADN/genética , Lipopolisacáridos , Hígado/metabolismo , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microvellosidades/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Triglicéridos/metabolismoRESUMEN
OBJECTIVE: To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile. BACKGROUND: The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections. METHODS: C57BL/6 mice were treated with antibiotic(s) ± cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes. RESULTS: We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival. CONCLUSIONS: Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans.
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Fosfatasa Alcalina/uso terapéutico , Antibacterianos/efectos adversos , Clostridioides difficile , Infecciones por Clostridium/prevención & control , Fármacos Gastrointestinales/uso terapéutico , Infecciones por Salmonella/prevención & control , Salmonella typhimurium , Administración Oral , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/farmacología , Animales , Antibacterianos/administración & dosificación , Biomarcadores/metabolismo , Infecciones por Clostridium/etiología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/microbiología , Diarrea/etiología , Diarrea/prevención & control , Femenino , Fármacos Gastrointestinales/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Ratones , Ratones Endogámicos C57BL , Infecciones por Salmonella/etiología , Estreptomicina/administración & dosificación , Estreptomicina/efectos adversos , Resultado del TratamientoRESUMEN
All disasters are local but implementing a hyperlocal response in the midst of a public health emergency is challenging. The availability of neighborhood-level qualitative data that are both timely and relevant to evolving objectives and operations is a limiting factor. In 2020, the New York City Department of Health and Mental Hygiene (NYC DOHMH) responded to the COVID-19 emergency using a novel, hyperlocal approach. Key to the implementation of this approach was the creation of the Community Assessment to Inform Rapid Response (CAIRR), a process for rapid collection and analysis of neighborhood-specific, objective-focused, qualitative data to inform tailored response operations. This paper describes the process of developing the CAIRR and its contribution to the NYC DOHMH's hyperlocal response in order to guide other jurisdictions seeking to employ a hyperlocal approach in future disaster responses.
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COVID-19 , Desastres , Humanos , COVID-19/epidemiología , Ciudad de Nueva York/epidemiología , Salud Pública , Recolección de DatosRESUMEN
Importance: Contact tracing is a core strategy for preventing the spread of many infectious diseases of public health concern. Better understanding of the outcomes of contact tracing for COVID-19 as well as the operational opportunities and challenges in establishing a program for a jurisdiction as large as New York City (NYC) is important for the evaluation of this strategy. Objective: To describe the establishment, scaling, and maintenance of Trace, NYC's contact tracing program, and share data on outcomes during its first 17 months. Design, Setting, and Participants: This cross-sectional study included people with laboratory test-confirmed and probable COVID-19 and their contacts in NYC between June 1, 2020, and October 31, 2021. Trace launched on June 1, 2020, and had a workforce of 4147 contact tracers, with the majority of the workforce performing their jobs completely remotely. Data were analyzed in March 2022. Main Outcomes and Measures: Number and proportion of persons with COVID-19 and contacts on whom investigations were attempted and completed; timeliness of interviews relative to symptom onset or exposure for symptomatic cases and contacts, respectively. Results: Case investigations were attempted for 941â¯035 persons. Of those, 840â¯922 (89.4%) were reached and 711â¯353 (75.6%) completed an intake interview (women and girls, 358â¯775 [50.4%]; 60â¯178 [8.5%] Asian, 110â¯636 [15.6%] Black, 210â¯489 [28.3%] Hispanic or Latino, 157â¯349 [22.1%] White). Interviews were attempted for 1â¯218â¯650 contacts. Of those, 904â¯927 (74.3%) were reached, and 590â¯333 (48.4%) completed intake (women and girls, 219â¯261 [37.2%]; 47â¯403 [8.0%] Asian, 98â¯916 [16.8%] Black, 177â¯600 [30.1%] Hispanic or Latino, 116â¯559 [19.7%] White). Completion rates were consistent over time and resistant to changes related to vaccination as well as isolation and quarantine guidance. Among symptomatic cases, median time from symptom onset to intake completion was 4.7 days; a median 1.4 contacts were identified per case. Median time from contacts' last date of exposure to intake completion was 2.3 days. Among contacts, 30.1% were tested within 14 days of notification. Among cases, 27.8% were known to Trace as contacts. The overall expense for Trace from May 6, 2020, through October 31, 2021, was approximately $600 million. Conclusions and Relevance: Despite the complexity of developing a contact tracing program in a diverse city with a population of over 8 million people, in this case study we were able to identify 1.4 contacts per case and offer resources to safely isolate and quarantine to over 1 million cases and contacts in this study period.
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COVID-19 , Trazado de Contacto , Femenino , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Ciudad de Nueva York/epidemiología , Estudios Transversales , CuarentenaRESUMEN
Recent breakthroughs in the fundamental understanding of the cellular and molecular basis of melanoma have culminated in new therapies with unquestionable efficacy. Immunotherapy and targeted therapy strategies have completely transformed the contemporary management of advanced melanoma. The translational research behind these developments is discussed, with an emphasis on immune checkpoint blockade and inhibition of the mitogen-activated protein kinase signaling pathway.