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1.
J Am Chem Soc ; 146(22): 15143-15154, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38781282

RESUMEN

Nickel and palladium complexes bearing "sandwich" diimine ligands with perfluorinated aryl caps have been synthesized, characterized, and explored in ethylene polymerization reactions. The X-ray crystallographic analysis of the precatalysts 16 and 6b shows differences from their nonfluorinated analogues 17 and 19, with the perfluorinated aryl caps centered precisely over the nickel and palladium centers, which results in higher buried volumes of the metal centers relative to the nonfluorinated analogues. The sandwich diimine-palladium complexes 5a and 5b containing perfluorinated aryl caps polymerize ethylene in a controlled fashion with activities that are substantially increased compared with their nonfluorinated analogues. Migratory insertion rates in relevant methyl ethylene complexes agree with the activities exhibited in bulk polymerization experiments. DFT studies suggest that facility of ethylene rotation from its preferred orientation perpendicular to the Pd-alkyl bond into a parallel in-plane conformation contributes to the higher polymerization activity for 5b relative to 18a. For these palladium systems, polymer molecular weights can be controlled via hydrogen addition (hydrogenolysis), which is unusual for late-transition-metal-catalyzed olefin polymerizations with no catalyst deactivation occurring. Sandwich diimine-nickel complexes 6a and 6b with perfluorinated aryl caps show ethylene polymerization activities that are about half of those of classical tetraisopropyl-substituted catalyst 2 but again are more active than the analogous nonfluorinated sandwich complexes. Ethylene polymerizations exhibit living behavior, and branched ultrahigh-molecular-weight polyethylenes (UHMWPEs) with very low-molecular-weight distributions (less than 1.1) are obtained. The activated nickel catalysts are stable in the absence of monomer and show good long-term stability at 25 °C.

2.
Lancet ; 397(10272): 398-408, 2021 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-33516338

RESUMEN

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.


Asunto(s)
Control de Enfermedades Transmisibles , Enfermedades Transmisibles/mortalidad , Enfermedades Transmisibles/virología , Modelos Teóricos , Mortalidad/tendencias , Años de Vida Ajustados por Calidad de Vida , Vacunación , Preescolar , Control de Enfermedades Transmisibles/economía , Control de Enfermedades Transmisibles/estadística & datos numéricos , Enfermedades Transmisibles/economía , Análisis Costo-Beneficio , Países en Desarrollo , Femenino , Salud Global , Humanos , Programas de Inmunización , Masculino , Vacunación/economía , Vacunación/estadística & datos numéricos
3.
BMC Med ; 20(1): 202, 2022 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-35705986

RESUMEN

BACKGROUND: Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response. METHODS: We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus. RESULTS: Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0-3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0-8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination. CONCLUSIONS: Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.


Asunto(s)
Epidemias , Coronavirus del Síndrome Respiratorio de Oriente Medio , Vacunas , Animales , Brotes de Enfermedades/prevención & control , Epidemias/prevención & control , Humanos , Zoonosis/epidemiología , Zoonosis/prevención & control
4.
J Org Chem ; 87(22): 14995-15000, 2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36318665

RESUMEN

While the 1,5-sigmatropic hydrogen shift in cyclopentadiene is generally thought to be a unimolecular pericyclic reaction, Yamabe proposed a more complex bimolecular mechanism proceeding through the exo dimer of cyclopentadiene. DFT computations by Yamabe were claimed to show that the bimolecular mechanism was kinetically more favorable than the unimolecular mechanism. Reinvestigation of the unimolecular concerted mechanism and Yamabe's bimolecular mechanism with ωB97X-D and DLPNO-CCSD(T) calculations demonstrates a 25 kcal/mol preference for the unimolecular mechanism relative to the bimolecular mechanism. While Yamabe's calculations were performed with the less accurate B3LYP functional, the incorrect conclusion was the result of a different error discovered here. We have also computed corrections for tunneling that result in computed activation barriers within 1.5 kcal/mol of the experimental values.


Asunto(s)
Ciclopentanos , Hidrógeno
5.
Violence Vict ; 36(3): 401-423, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34103414

RESUMEN

Most teen dating violence (TDV) victims do not seek help after their victimization experience. While research has identified that victims are more likely to turn to informal versus formal sources, there is a lack of knowledge about what factors are predictive of help-seeking from formal sources. The current study explored the impact of incident and victim characteristics on help-seeking from formal sources among middle and high school TDV victims (N = 2,174). Findings indicate that the severity and location of the victimization significantly increase the likelihood of help-seeking from formal sources.


Asunto(s)
Conducta del Adolescente , Acoso Escolar , Víctimas de Crimen , Violencia de Pareja , Adolescente , Humanos , Relaciones Interpersonales
6.
J Am Chem Soc ; 142(15): 7198-7206, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32233435

RESUMEN

New neutral nickel and palladium ethylene polymerization catalysts have been prepared that incorporate an anionic (N,O) chelating ligand. Extensive axial shielding is provided by two 3,5-dichloroaryl moieties in a "sandwich" orientation. Such shielding results in an exceptionally slow rate of chain transfer relative to migratory insertion in the nickel catalyst, and thus highly controlled polymerization of ethylene is observed, leading to lightly branched ultra-high molecular weight polyethylene with Mn values up to 4.1 × 106 g/mol. The analogous palladium catalysts provide the means for a detailed mechanistic study of chain propagation in an electronically asymmetric neutral palladium catalyst. Both isomers of the methyl ethylene complex can be generated and observed at low temperatures allowing experimental elucidation of mechanistic details of chain propagation probed in other electronically asymmetric systems only through DFT studies or by examination of model studies. The barrier to migratory insertion in these complexes is ca. 19.2 kcal/mol. Investigation of the equilibration of the methyl ethylene isomers in the presence of excess ethylene showed the isomerization rate is dependent on ethylene concentration. This is the first direct proof that isomerization in these alkyl ethylene intermediates is catalyzed by ethylene. Furthermore, isomer equilibration is much faster than migratory insertion so that the barriers for insertion of individual isomers cannot be determined.

7.
J Asian Nat Prod Res ; 22(12): 1152-1158, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31769308

RESUMEN

From EtOAc-soluble fraction of the aerial parts of Ampelopsis cantoniensis (Vitaceae), two new meroterpenoids named ampechromonol A (1) and ampechromonol B (2), together with five known compounds (3-7), were isolated. Their structures were elucidated based on NMR spectroscopic analysis. The plausible biosynthesis pathway for the formation of two new meroterpenoids was proposed. This research is the first isolation of meroterpenoids from Ampelopsis genus. Compounds 1 and 2 showed weak cytotoxicity against MCF-7 breast cancer cells.


Asunto(s)
Ampelopsis , Vitaceae , Estructura Molecular , Componentes Aéreos de las Plantas
8.
J Asian Nat Prod Res ; 21(9): 867-872, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29986612

RESUMEN

From an EtOAc-soluble fraction of the leaves of Azadirachta indica, two new 28-norlimonoids named nimbandiolactone-21 (1) and nimbandioloxyfuran (2), together with nimbandiolactone-23 (3), were isolated. Their relative structures were elucidated based on NMR spectroscopic interpretation and biosynthetic consideration. Nimbandioloxyfuran (2) and nimbandiolactone-23 (3) showed potent α-glucosidase inhibitory activity, with the IC50 values of 46.2 and 38.7 µM, respectively.


Asunto(s)
Azadirachta/química , Limoninas/química , Hojas de la Planta/química , Estructura Molecular
9.
Lancet ; 387(10026): 1405-1414, 2016 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-26719230

RESUMEN

BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18-75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0-2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0-1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m(2) pemetrexed plus 75 mg/m(2) cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. FINDINGS: From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9-22·6]) than with PC (16·1 months [14·0-17·9]; hazard ratio 0·77 [0·62-0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3-4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. INTERPRETATION: Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease. FUNDING: Intergroupe Francophone de Cancérologie Thoracique (IFCT).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Pemetrexed/administración & dosificación , Neoplasias Pleurales/tratamiento farmacológico , Anciano , Bevacizumab/efectos adversos , Cisplatino/efectos adversos , Creatinina/sangre , Femenino , Humanos , Hipertensión/epidemiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/mortalidad , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Pemetrexed/efectos adversos , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Proteinuria/epidemiología , Trombosis/epidemiología , Factor A de Crecimiento Endotelial Vascular/sangre
10.
Lancet ; 387(10026): 1415-1426, 2016 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-26777916

RESUMEN

BACKGROUND: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. METHODS: This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. FINDINGS: 18,679 molecular analyses of 17,664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18-98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7-16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17,706 analyses for which data were available, HER2 mutations in 98 (1%) of 11,723, KRAS mutations in 4894 (29%) of 17,001, BRAF mutations in 262 (2%) of 13,906, and PIK3CA mutations in 252 (2%) of 10,678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8-25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7-38·2] for presence of a genetic alteration vs 33% [29·5-35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0-18·8] vs 9% [6·7-11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2-10·7] vs 7·1 months [6·1-7·9]; p<0·0001) and overall survival (16·5 months [15·0-18·3] vs 11·8 months [10·1-13·5]; p<0·0001) compared with absence of a genetic alteration. INTERPRETATION: Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit. FUNDING: French National Cancer Institute (INCa).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Fosfatidilinositol 3-Quinasa Clase I , Receptores ErbB/genética , Femenino , Francia/epidemiología , Reordenamiento Génico , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Fosfatidilinositol 3-Quinasas/genética , Estudios Prospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Tirosina Quinasas Receptoras/genética , Receptor ErbB-2/genética , Adulto Joven
11.
BMC Public Health ; 16: 28, 2016 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-26758034

RESUMEN

BACKGROUND: Effective control of sexually transmitted infections (STIs) depends on affected patients notifying their sexual partners, and partners following through with screening and treatment. Our study assessed high-risk-STI women's confidence in STI-diagnosis-related communications with their primary male partners in Ho Chi Minh City, Vietnam, and determined associated characteristics of the women and their partners. METHODS: We employed convenience and snowball sampling in a clinic-based setting to recruit 126 women from August to October 2013. All data were obtained from women's self-report. RESULTS: The proportions of participants who were "slightly confident" or "very confident" that they could disclose their STI positivity to partners, ask partners to have an STI examination or treatment, and give partners bacterial-STI medications were 70.3%, 62.1%, and 69.0%, respectively. The proportions who perceived that their partners would be "very likely" to have an STI examination and to take STI medications were 16.2% and 38.8%, respectively. Significantly lower self-efficacy was observed in women who had a lower education level, who had ever traded sex, or whose primary partners were not husbands or fiancés. CONCLUSIONS: Our results suggest potential for piloting STI-partner-targeted interventions. To be effective, these programs should improve women's self-efficacy and primary partners' cooperation with screening and treatment.


Asunto(s)
Comunicación , Revelación/estadística & datos numéricos , Autoeficacia , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Relaciones Interpersonales , Persona de Mediana Edad , Trabajadores Sexuales/estadística & datos numéricos , Parejas Sexuales , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Factores Socioeconómicos , Vietnam/epidemiología , Adulto Joven
12.
J Org Chem ; 80(1): 256-65, 2015 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-25437898

RESUMEN

A series of 2'-arylbenzaldehyde oxime ethers were synthesized and shown to generate the corresponding phenanthridines upon irradiation in the presence of 9,10-dicyanoanthracene in acetonitrile. Mechanistic studies suggest that the oxidative cyclization reaction sequence is initiated by an electron transfer step followed by nucleophilic attack of the aryl ring onto the nitrogen of the oxime ether. A concave downward Hammett plot is presumably the result of a change in charge distribution in the radical cation species with strongly electron-donating substituents that yields a less electrophilic nitrogen atom and a decreased amount of cyclized product. The reaction is selective (no nitrile byproduct is formed unlike other photochemical reactions involving aldoxime ethers) as well as regiospecific when using 2'-aryl groups with meta-substituents, making this reaction a useful alternative for preparing substituted phenanthridines.

13.
Nano Lett ; 12(11): 5455-63, 2012 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-23043427

RESUMEN

The emergence of new technologies, such as whole genome sequencing systems, which generate a large amount of data, is requiring ultrahigh storage capacities. Due to their compactness and low power consumption, probe-based memory devices using Pb(Zr(0.2)Ti(0.8))O(3) (PZT) ferroelectric films are the ideal candidate for such applications where portability is desired. To achieve ultrahigh (>1 Tbit/in(2)) storage densities, sub-10 nm inverted domains are required. However, such domains remain unstable and can invert back to their original polarization due to the effects of an antiparallel built-in electric field in the PZT film, domain-wall, and depolarization energies. Here, we show that the built-in electric-field can be tuned and suppressed by repetitive hydrogen and oxygen plasma treatments. Such treatments trigger reversible Pb reduction/oxidation activity, which alters the electrochemistry of the Pb overlayer and compensates for charges induced by the Pb vacancies. This tuning mechanism is used to demonstrate the writing of stable and equal size sub-4 nm domains in both up- and down-polarized PZT films, corresponding to eight inverted unit-cells. The bit sizes recorded here are the smallest ever achieved, which correspond to potential 60 Tbit/in(2) data storage densities.


Asunto(s)
Nanotecnología/métodos , Electricidad , Electroquímica/métodos , Diseño de Equipo , Genoma , Hidrógeno/química , Plomo/química , Modelos Estadísticos , Oxígeno/química , Física/métodos , Análisis de Secuencia de ADN/instrumentación , Temperatura , Titanio/química , Circonio/química
14.
Heliyon ; 9(8): e19000, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37636424

RESUMEN

Income inequality is a vexing developmental challenge for governments and policymakers as it impedes social transformation and economic growth and development. Meanwhile, promoting financial development is generally regarded as an effective way to achieve inclusive and sustainable growth. This study examines the long-run effects of financial development, economic growth, and their combined effects on income inequality for 12 Asia-Pacific countries from 1990 to 2021. This paper employs various econometric techniques and different financial development proxies to ensure the findings' robustness. The paper also constructs a financial development index using the principal component analysis to fully capture the comprehensive effect of financial development on income inequality. Empirical results reveal that the impact of financial development on income inequality follows the inverted U-shaped relationship - financial development widens income inequality and only reduces income when surpassing its turning point. Findings further reveal that the nonlinear effect of financial development on income inequality is contingent upon the level of per capita income. Thus, policies promoting financial development to reduce income inequality should consider the existing level of per capita income.

15.
Vaccine ; 41(1): 182-192, 2023 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-36424258

RESUMEN

In recent decades, there has been an increased interest in developing a vaccine for chikungunya. However, due to its unpredictable transmission, planning for a chikungunya vaccine trial is challenging. To inform decision making on the selection of sites for a vaccine efficacy trial, we developed a new framework for projecting the expected number of endpoint events at a given site. In this framework, we first accounted for population immunity using serological data collated from a systematic review and used it to estimate parameters related to the timing and size of past outbreaks, as predicted by an SIR transmission model. Then, we used that model to project the infection attack rate of a hypothetical future outbreak, in the event that one were to occur at the time of a future trial. This informed projections of how many endpoint events could be expected if a trial were to take place at that site. Our results suggest that some sites may have sufficient transmission potential and susceptibility to support future vaccine trials, in the event that an outbreak were to occur at those sites. In general, we conclude that sites that have experienced outbreaks within the past 10 years may be poorer targets for chikungunya vaccine efficacy trials in the near future. Our framework also generates projections of the numbers of endpoint events by age, which could inform study participant recruitment efforts.


Asunto(s)
Fiebre Chikungunya , Vacunas , Humanos , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/prevención & control , Predicción , Brotes de Enfermedades/prevención & control
16.
Crit Rev Oncol Hematol ; 190: 104112, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37633348

RESUMEN

Oral squamous cell carcinoma (OSCC) in non-smoking and non-drinking (NSND) individuals appears to be distinct from the traditional head and neck squamous cell carcinoma (HNSCC). The incidence of this subset is increasing, as are the number of studies examining its characteristics. NSND OSCC individuals tend to be younger (<45 years) compared to traditional HNSCC patients. The proportion of females in the NSND OSCC cohort is also higher. The tongue is the predominantly affected subsite. Studies have revealed several gene mutations and unique epigenomic profiles but no definitive genetic etiology. Transcriptomic analysis has not found any causative viral agents. Other proposed etiologies include chronic dental trauma, microbiome abnormalities, marijuana consumption, and genetic disorders. There are international efforts to determine the relative prognostic outcome of this unique cohort, but no consensus has been reached. Here, we review the incidence, demographics, subsite, possible etiologies, prognosis, and therapy implications of the NSND OSCC cohort.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Femenino , Humanos , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia
17.
BMJ Glob Health ; 8(8)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37652566

RESUMEN

New vector-control technologies to fight mosquito-borne diseases are urgently needed, the adoption of which depends on efficacy estimates from large-scale cluster-randomised trials (CRTs). The release of Wolbachia-infected mosquitoes is one promising strategy to curb dengue virus (DENV) transmission, and a recent CRT reported impressive reductions in dengue incidence following the release of these mosquitoes. Such trials can be affected by multiple sources of bias, however. We used mathematical models of DENV transmission during a CRT of Wolbachia-infected mosquitoes to explore three such biases: human movement, mosquito movement and coupled transmission dynamics between trial arms. We show that failure to account for each of these biases would lead to underestimated efficacy, and that the majority of this underestimation is due to a heretofore unrecognised bias caused by transmission coupling. Taken together, our findings suggest that Wolbachia-infected mosquitoes could be even more promising than the recent CRT suggested. By emphasising the importance of accounting for transmission coupling between arms, which requires a mathematical model, we highlight the key role that models can play in interpreting and extrapolating the results from trials of vector control interventions.


Asunto(s)
Enfermedades Transmitidas por Vectores , Animales , Humanos , Enfermedades Transmitidas por Vectores/prevención & control , Enfermedades Transmitidas por Vectores/transmisión , Culicidae , Sesgo , Modelos Biológicos
18.
Front Endocrinol (Lausanne) ; 14: 1184360, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37435481

RESUMEN

G protein-coupled receptors (GPCRs) represent the target for approximately a third of FDA-approved small molecule drugs. The adenosine A1 receptor (A1R), one of four adenosine GPCR subtypes, has important (patho)physiological roles in humans. A1R has well-established roles in the regulation of the cardiovascular and nervous systems, where it has been identified as a potential therapeutic target for a number of conditions, including cardiac ischemia-reperfusion injury, cognition, epilepsy, and neuropathic pain. A1R small molecule drugs, typically orthosteric ligands, have undergone clinical trials. To date, none have progressed into the clinic, predominantly due to dose-limiting unwanted effects. The development of A1R allosteric modulators that target a topographically distinct binding site represent a promising approach to overcome current limitations. Pharmacological parameters of allosteric ligands, including affinity, efficacy and cooperativity, can be optimized to regulate A1R activity with high subtype, spatial and temporal selectivity. This review aims to offer insights into the A1R as a potential therapeutic target and highlight recent advances in the structural understanding of A1R allosteric modulation.


Asunto(s)
Cognición , Receptor de Adenosina A1 , Humanos , Adenosina , Sitios de Unión , Corazón , Ligandos
19.
Sci Total Environ ; 895: 165145, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37385491

RESUMEN

Microplastics (MPs), which are ubiquitous, are no longer novel emerging pollutants, yet our knowledge of them is insufficient. This study investigates the prevalence of MPs and trace metals in sediment belonging to Ma River, Vietnam, and their interaction with various parameters, including nutrients such as total carbon (TC), total nitrogen (TN), and total phosphorus (TP), grain sizes, and MPs in surface water. The study revealed that the abundance of MPs in sediment (MPs/S) is relatively high (i.e., 1328.3 ± 1925.5 items.kg-1 dry weight), while the concentration of MPs in surface water (MPs/W) was relatively low (i.e., 57.3 ± 55.8 items.m-3) compared to other areas. Notably, the study found that arsenic and cadmium concentrations exceeded baseline levels, indicating their anthropogenic origin. To interpret the relationship between MPs/S, metals, and the aforementioned parameters, principal component analysis and Pearson correlation analyses were employed. The results demonstrated a significant correlation between metals and nutrients, as well as small grain sizes such as clay and silt. It was observed that the majority of metals displayed co-occurrence with one another but showed weak associations with the levels of MPs present in both water and sediment. Additionally, a weak correlation was observed between MPs/W and MPs/S. In conclusion, these findings suggest that the distribution and behavior of MPs and trace metals in aquatic systems are influenced by multiple factors, including nutrient levels, grain size, and other chemical and physical characteristics of the environment. While certain metals may have natural sources, others may result from human activities such as mining, industrial discharge, and wastewater treatment plants. As a result, understanding the sources and aspects of metal contamination are critical for determining their relationship with MPs and developing effective strategies for mitigating their impact on aquatic ecosystems.

20.
PLoS One ; 17(6): e0268631, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35709183

RESUMEN

The trade agreement is generally considered an effective mechanism to encourage trading activities. However, trade activities may lead to environmental degradation because more trade is generally associated with more energy consumption. In addition, financial development with an increased flow of capital among members is required to fund trading activities. Renewable energy can be a moderating factor to balance the effects of trade activities and financial development on the economy and the environment. This paper focuses on the inter-relationship between growth-energy-finance nexus for the CPTPP members in the 1971-2020 period. While the energy-growth-environment nexus has been extensively investigated, the energy-growth-finance relationship has been largely ignored in existing literature, particularly for the CPTPP countries. Our findings can be summarized as follows. First, we find that renewable energy consumption does reduce CO2 emission while financial development does not necessarily increase environmental degradation. Second, financial development is found to cause renewable energy usage bilaterally. Finally, when different proxies are used for financial development, a bilateral causality relationship between renewable energy usage, financial development and economic growth is confirmed. These important findings imply that the governments of the CPTPP countries should encourage renewable energy usage to achieve the dual objectives from the CPTPP trade agreement: (i) to increase trade activities; and (ii) to support further financial development within the region. These two objectives together support economic growth.


Asunto(s)
Desarrollo Económico , Administración Financiera , Dióxido de Carbono , Energía Renovable
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