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Speciation is often driven by selective processes like those associated with viability, mate choice, or local adaptation, and "speciation genes" have been identified in many eukaryotic lineages. In contrast, neutral processes are rarely considered as the primary drivers of speciation, especially over short evolutionary timeframes. Here, we describe a rapid vertebrate speciation event driven primarily by genetic drift. The White Sands pupfish (Cyprinodon tularosa) is endemic to New Mexico's Tularosa Basin where the species is currently managed as two Evolutionarily significant units (ESUs) and is of international conservation concern (Endangered). Whole-genome resequencing data from each ESU showed remarkably high and uniform levels of differentiation across the entire genome (global FST ≈ 0.40). Despite inhabiting ecologically dissimilar springs and streams, our whole-genome analysis revealed no discrete islands of divergence indicative of strong selection, even when we focused on an array of candidate genes. Demographic modeling of the joint allele frequency spectrum indicates the two ESUs split only ~4 to 5 kya and that both ESUs have undergone major bottlenecks within the last 2.5 millennia. Our results indicate the genome-wide disparities between the two ESUs are not driven by divergent selection but by neutral drift due to small population sizes, geographic isolation, and repeated bottlenecks. While rapid speciation is often driven by natural or sexual selection, here we show that isolation and drift have led to speciation within a few thousand generations. We discuss these evolutionary insights in light of the conservation management challenges they pose.
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Flujo Genético , Especiación Genética , Animales , Peces Killi/genética , Peces Killi/clasificación , New Mexico , Selección Genética , Frecuencia de los Genes , Genoma/genéticaRESUMEN
Even in large systems, the effect of noise arising from when populations are initially small can persist to be measurable on the macroscale. A deterministic approximation to a stochastic model will fail to capture this effect, but it can be accurately approximated by including an additional random time-shift to the initial conditions. We present a efficient numerical method to compute this time-shift distribution for a large class of stochastic models. The method relies on differentiation of certain functional equations, which we show can be effectively automated by deriving rules for different types of model rates that arise commonly when mass-action mixing is assumed. Explicit computation of the time-shift distribution can be used to build a practical tool for the efficient generation of macroscopic trajectories of stochastic population models, without the need for costly stochastic simulations. Full code is provided to implement the calculations and we demonstrate the method on an epidemic model and a model of within-host viral dynamics.
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Simulación por Computador , Epidemias , Conceptos Matemáticos , Modelos Biológicos , Dinámica Poblacional , Procesos Estocásticos , Humanos , Epidemias/estadística & datos numéricos , Dinámica Poblacional/estadística & datos numéricos , Factores de TiempoRESUMEN
Previous work has shown how a minimal ecological structure consisting of patchily distributed resources and recurrent dispersal between patches can scaffold Darwinian properties onto collections of cells. When the timescale of dispersal is long compared with the time to consume resources, patch fitness increases but comes at a cost to cell growth rates. This creates conditions that initiate evolutionary transitions in individuality. A key feature of the scaffold is a bottleneck created during dispersal, causing patches to be founded by single cells. The bottleneck decreases competition within patches and, hence, creates a strong hereditary link at the level of patches. Here, we construct a fully stochastic model to investigate the effect of bottleneck size on the evolutionary dynamics of both cells and collectives. We show that larger bottlenecks simply slow the dynamics, but, at some point, which depends on the parameters of the within-patch model, the direction of evolution towards the equilibrium reverses. Introduction of random fluctuations in bottleneck sizes with some positive probability of smaller sizes counteracts this, even when the probability of smaller bottlenecks is minimal.
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Evolución Biológica , Dinámica Poblacional , ProbabilidadRESUMEN
BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings. The aim of this study was to identify the implementation barriers to and facilitators of the detection of FH in Australia. METHODS: Four, 2-hour virtual focus groups were facilitated by implementation scientists and a clinicians as part of the 2021 Australasian FH Summit. Template analysis was used to identify themes. RESULTS: There were 28 workshop attendees across four groups (n=6-8 each), yielding 13 barriers and 10 facilitators across three themes: (1) patient related, (2) provider related, and (3) system related. A "lack of care pathways" and "upskilling clinicians in identifying and diagnosing FH" were the most interconnected barriers and facilitators for the detection of FH. CONCLUSIONS: The relationships between barriers and facilitators across the patient, provider, and system themes indicates that a comprehensive implementation strategy is needed to address these different levels. Future research is underway to develop a model for implementing the Australian FH guidelines into practice.
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Hiperlipoproteinemia Tipo II , Humanos , Australia/epidemiología , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/terapia , Progresión de la Enfermedad , Tamizaje MasivoRESUMEN
Objective: To synthesize learnings from four national tobacco control investment cases conducted in the Americas (Colombia, Costa Rica, El Salvador, Suriname) under the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) 2030 project, to describe results and how national health authorities have used the cases, and to discuss implications for the role of investment cases in advancing tobacco control. Methods: We draw on findings from four national investment cases that included 1) a cost-of-illness analysis calculating the health and economic burden of tobacco use, 2) a return-on-investment analysis of implementing key tobacco control demand reduction measures, and 3) a subsidiary analysis of one tobacco control topic of national interest (e.g., equity implications of cigarette taxation). Co-authors reported how cases have been used to advance tobacco control. Results: In Colombia, Costa Rica, El Salvador, and Suriname, tobacco use causes social and economic losses equivalent to between 1.0 to 1.8 percent of GDP. Across these countries, implementing WHO FCTC demand reduction measures would save an average of 11 400 lives per year over the next 15 years. Benefits of the measures would far outweigh the costs of implementation and enforcement. Governments are using the cases to advance tobacco control, including to improve tobacco control laws and their enforcement, strengthen tobacco taxation, prioritize tobacco control planning, coordinate a multisectoral response, and engage political leaders. Conclusions: National investment cases can help to strengthen tobacco control in countries, including by increasing public and political support for implementation of the WHO FCTC and by informing effective planning, legislation, coordination and financing.
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The ability of health systems to cope with coronavirus disease (COVID-19) cases is of major concern. In preparation, we used clinical pathway models to estimate healthcare requirements for COVID-19 patients in the context of broader public health measures in Australia. An age- and risk-stratified transmission model of COVID-19 demonstrated that an unmitigated epidemic would dramatically exceed the capacity of the health system of Australia over a prolonged period. Case isolation and contact quarantine alone are insufficient to constrain healthcare needs within feasible levels of expansion of health sector capacity. Overlaid social restrictions must be applied over the course of the epidemic to ensure systems do not become overwhelmed and essential health sector functions, including care of COVID-19 patients, can be maintained. Attention to the full pathway of clinical care is needed, along with ongoing strengthening of capacity.
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COVID-19/transmisión , Capacidad de Camas en Hospitales/estadística & datos numéricos , Pandemias/prevención & control , Capacidad de Reacción/organización & administración , Australia/epidemiología , COVID-19/epidemiología , Trazado de Contacto , Vías Clínicas/normas , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Distanciamiento Físico , Salud Pública , Cuarentena/métodosRESUMEN
N-(2-chloro-5-(S-2-[18 F]fluoroethyl)thiophenyl)-N'-(3-thiomethylphenyl)-N'-methylguanidine, ([18 F]GE-179), has been identified as a promising positron emission tomography (PET) ligand for the intra-channel phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA) receptor. The radiosynthesis of [18 F]GE-179 has only been performed at low radioactivity levels. However, the manufacture of a GMP compliant product at high radioactivity levels was required for clinical studies. We describe the development of a process using the GE FASTlab™ radiosynthesis platform coupled with HPLC purification. The radiosynthesis is a two-step process, involving the nucleophilic fluorination of ethylene ditosylate, 11, followed by alkylation to the deprotonated thiol precursor, N-(2-chloro-5-thiophenol)-N'-(3-thiomethylphenyl)-N'-methyl guanidine, 8. The crude product was purified by semi-preparative HPLC to give the formulated product in an activity yield (AY) of 7 ± 2% (n = 15) with a total synthesis time of 120 minutes. The radioactive concentration (RAC) and radiochemical purity (RCP) were 328 ± 77 MBq/mL and 96.5 ± 1% respectively and the total chemical content was 2 ± 1 µg. The final formulation volume was 14 mL. The previously described radiosynthesis of [18 F]GE-179 was successfully modified to deliver an process on the FASTlab™ that allows the manufacture of a GMP quality product from high starting radioactivitity (up to 80 GBq) and delivers a product suitable for clinical use.
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Radioquímica/métodos , Receptores de N-Metil-D-Aspartato/metabolismo , Automatización , HumanosRESUMEN
BACKGROUND: In 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes. METHODS: We retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011-06/2012 (early cohort) and 07/2013-06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city's four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes. RESULTS: Five hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high. Although TTI reduced by a median of 19 days, from 33 days (IQR 12-52) in the early cohort to 14 days (IQR 7-31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation. CONCLUSION: Pre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.
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Antibióticos Antituberculosos/uso terapéutico , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Anciano , Estudios de Cohortes , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis , Sector Público , Derivación y Consulta , Estudios Retrospectivos , Sudáfrica , Tiempo de Tratamiento , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/diagnósticoRESUMEN
South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with human immunodeficiency virus (HIV). The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for the initial diagnosis of TB, and other molecular platforms such as the m2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV load. The latter platform is now also equipped with the RealTime (RT) MTB and RealTime MTB RIF/INH assays for TB and first-line drug resistance screening but has not been evaluated in settings of HIV and TB coinfection. A prospective clinical validation study was conducted at a community health center in Johannesburg, South Africa, and consenting individuals with presumptive pulmonary TB were enrolled. The performance of the Abbott assays was compared with those of the Xpert MTB/RIF, liquid culture, drug susceptibility testing, and clinical case definitions. A statistical analysis was performed on 206 individuals (73% were HIV positive). The sensitivity and specificity of the RT MTB were 82.5% (confidence interval [CI], 67.2 to 92.7) and 93.1% (CI, 86.2 to 97.2) on raw sputum and 77.5% (CI, 61.5 to 89.2) and 95.1% (CI, 88.9 to 98.4) on concentrated sputum, respectively, compared with those from liquid culture. The RT MTB correctly identified 17/35 more smear-negative culture-positive specimens than the Xpert MTB/RIF. Both the RT MTB and the Xpert MTB/RIF displayed sensitivities >70% and specificities >90% in HIV-positive individuals. The available drug resistance results concurred with MTBDRplus and drug susceptibility profiles. The RT MTB assay has similar diagnostic performance to the Xpert MTB/RIF and is suited to testing presumptive TB patients coinfected with HIV. The existing laboratory information system connectivity, training, and technical support make this a viable polyvalent option to scale up TB alongside HIV laboratory testing services in South Africa.
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Coinfección/diagnóstico , Técnicas de Genotipaje/métodos , Infecciones por VIH/complicaciones , Pruebas de Sensibilidad Microbiana/métodos , Técnicas de Diagnóstico Molecular/métodos , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Sudáfrica , Adulto JovenRESUMEN
The Leon Springs pupfish (Cyprinodon bovinus) is an endangered species currently restricted to a single desert spring and a separate captive habitat in southwestern North America. Following establishment of the captive population from wild stock in 1976, the wild population has undergone natural population size fluctuations, intentional culling to purge genetic contamination from an invasive congener (Cyprinodon variegatus) and augmentation/replacement of wild fish from the captive stock. A severe population decline following the most recent introduction of captive fish prompted us to examine whether the captive and wild populations have differentiated during the short time they have been isolated from one another. If so, the development of divergent genetic and/or morphologic traits between populations could contribute to a diminished ability of fish from one location to thrive in the other. Examination of genomewide single nucleotide polymorphisms and morphologic variation revealed no evidence of residual C. variegatus characteristics in contemporary C. bovinus samples. However, significant genetic and morphologic differentiation was detected between the wild and captive populations, some of which might reflect local adaptation. Our results indicate that genetic and physical characteristics can diverge rapidly between isolated subdivisions of managed populations, potentially compromising the value of captive stock for future supplementation efforts. In the case of C. bovinus, our findings underscore the need to periodically inoculate the captive population with wild genetic material to help mitigate genetic, and potentially morphologic, divergence between them and also highlight the utility of parallel morphologic and genomic evaluation to inform conservation management planning.
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Especies en Peligro de Extinción , Genética de Población , Peces Killi/genética , Polimorfismo de Nucleótido Simple , Animales , Conservación de los Recursos Naturales , Biblioteca de Genes , Peces Killi/anatomía & histología , New Mexico , Dinámica Poblacional , Análisis de Secuencia de ADN , TexasRESUMEN
BACKGROUND: First Nations (FNs) populations in Canada experience a disproportionally higher rate of obesity and type 2 diabetes (T2D) compared to the general population. Recent data suggest that a high consumption of fish may help prevent T2D. On the other hand, fish might also be a potential source of environmental contaminants which could potentially be a risk factor for T2D. OBJECTIVE: To investigate the potential associations between self-reported T2D and consumption of locally-harvested fish, dietary long-chain omega-3 fatty acids (n-3FAs) and persistent organic pollutants intake among adult FNs living on reserve in Ontario. DESIGN: Data from the First Nations Food Nutrition and Environment Study, which included a cross-sectional study of 1429 Ontario FNs adults living in 18 communities across 4 ecozones in 2012 were analyzed. Social and lifestyle data were collected using household interviews. The consumption of locally-harvested fish was estimated using a traditional food frequency questionnaire along with portion size information obtained from 24hr recalls. Fish samples were analyzed for the presence of contaminants including dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs). Dietary intakes of DDE and PCBs were estimated using community-specific levels of DDE/PCBs in fish species. Multiple logistic regression models adjusted for potential covariates including age, gender, body mass index, physical activity, total energy intake, smoking, and education were developed. RESULTS: The prevalence of T2D in Ontario FNs was 24.4%. A significant positive association between fish consumption of one portion per week and more and T2D compared to no fish consumption was found (OR=2.5 (95% CI: 1.38-4.58). Dietary DDE and PCBs intake was positively associated with T2D (OR=1.09 (95%CI: 1.05-1.75) for DDE and OR=1.07 (95%CI: 1.004-1.27) for PCBs) per unit increase in DDE/PCBs while n-3-FAs intake, adjusted for DDE/PCBs intake, showed an inverse effect against T2D among older individuals (OR=0.86 (95% CI: 0.46-0.99). CONCLUSION: Our results support previous findings that exposure to DDE and PCBs may increase the risk of T2D. Elevated levels of contaminants in fish may counteract with potentially beneficial effects of n-3FAs from fish consumption. However, the overall health benefits of high consumption of fish with a high n-3 FAs content may outweigh the adverse effect of contaminants.
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Diabetes Mellitus Tipo 2/epidemiología , Contaminantes Ambientales/análisis , Ácidos Grasos Omega-3 , Peces , Contaminación de Alimentos/análisis , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios Transversales , Dieta , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Indígenas Norteamericanos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Methyl Mercury (MeHg) exposure is a global environmental health concern. Indigenous peoples around the world are susceptible to MeHg exposure from often higher fish consumption compared to general populations. The objective of this study was to estimate dietary exposure to methylmercury (MeHg) among First Nations living on-reserve in the province of Ontario, Canada. A total diet study was constructed based on a 24-h recall from the First Nations Food, Nutrition, and Environment Study (FNFNES), and measured contaminant concentrations from Health Canada for market foods, and FNFNES for traditional foods. A probabilistic assessment of annual and seasonal traditional food consumptions was conducted for 1429 adult participants. Results were compared to exposures in the general Canadian population and reference values from Health Canada for adults and women of childbearing age (ages 19-50). Results indicated traditional foods to be the primary contributor to the dietary total MeHg intake (72%). The average dietary total MeHg exposure in the First Nations population in Ontario (0.039µg/kg/d) was 1.6 times higher than the general Canadian population; however, the majority (97.8%) of the population was below the reference values. Mercury concentrations in participants' hair samples (n = 744) ranged from 0.03 to 13.54µg/g, with an average of 0.64µg/g (geometric average of 0.27µg/g). Less than 1% of the population had a hair mercury value above the 6µg/g level, and 1.3% of women of child bearing age had values greater than 2µg/g. Fish species contributing to the MeHg intake included pickerel-walleye, pike, perch and trout. Only 7.9% of the population met the recommended fish consumption rate of two, 3.5oz servings per week from the American Heart Association. Therefore, consumption of lower trophic level fish can be promoted to provide the maximum nutritional benefit with minimal risk of MeHg exposure.
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Dieta , Exposición a Riesgos Ambientales , Contaminantes Ambientales/metabolismo , Compuestos de Metilmercurio/metabolismo , Encuestas sobre Dietas , Monitoreo del Ambiente , Cabello/química , Humanos , Indígenas Norteamericanos , Modelos Estadísticos , Ontario , Medición de RiesgoRESUMEN
BACKGROUND: Effective strategies to improve dietary intake in young children are a priority to reduce the high prevalence of chronic non-communicable diseases in adulthood. This study aimed to assess the impact of family-based and school/preschool nutrition programs on the health of children aged 12 or younger, including the sustainability of these impacts and the relevance to socio-economic inequalities. METHODS: A systematic review of literature published from 1980 to December 2014 was undertaken. Randomised controlled trials involving families with children aged up to 12 years in high income countries were included. The primary outcomes were dietary intake and health status. Results were presented in a narrative synthesis due to the heterogeneity of the interventions and outcomes. RESULTS: The systematic search and assessment identified 39 eligible studies. 82% of these studies were set in school/preschools. Only one school study assessed the impact of involving parents systematically. The family-based programs which provided simple positive dietary advice to parents and regular follow-up reduced fat intake significantly. School and family-based studies, if designed and implemented well, increased F&V intake, particularly fruit. Effective school-based programs have incorporated role-models including peers, teachers and heroic figures, rewards and increased access to healthy foods. School nutrition programs in disadvantaged communities were as effective as programs in other communities. CONCLUSIONS: Family and school nutrition programs can improve dietary intake, however evidence of the long-term sustainability of these impacts is limited. The modest overall impact of even these successful programs suggest complementary nutrition interventions are needed to build a supportive environment for healthy eating generally.
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Salud Infantil/estadística & datos numéricos , Dieta/estadística & datos numéricos , Familia , Promoción de la Salud/métodos , Servicios de Salud Escolar , Niño , Preescolar , Humanos , Evaluación de Programas y Proyectos de Salud , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. METHODS: We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. RESULTS: Across the two sites, 578 eligible patient files were reviewed. 36.7 % were categorized as low weight (≤50 kg) at DR-TB initiation. 76.0 % had no history of TB treatment prior to the current episode of RR TB. 26.8 % were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5 % of patients were also HIV positive, of whom 43.8 % were on ART prior to RR TB treatment and 32.1 % initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3 %) and 110 patients (19.0 %) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts ≤100 cells/mm3 and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95 % CI: 1.30-5.84 and sHR: 3.07, 95 % CI: 1.46-6.46, respectively). CONCLUSION: Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment.
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Antituberculosos/efectos adversos , Infecciones por VIH , Tuberculosis/tratamiento farmacológico , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Recuento de Linfocito CD4 , Niño , Estudios de Cohortes , Coinfección/tratamiento farmacológico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rifampin/uso terapéutico , Sudáfrica , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto JovenRESUMEN
Recently, pandemic response has involved the use of antivirals. These antivirals are often allocated to households dynamically throughout the pandemic with the aim being to retard the spread of infection. A drawback of this is that there is a delay until infection is confirmed and antivirals are delivered. Here an alternative allocation scheme is considered, where antivirals are instead preallocated to households at the start of a pandemic, thus reducing this delay. To compare these two schemes, a deterministic approximation to a novel stochastic household model is derived, which allows efficient computation of key quantities such as the expected epidemic final size, expected early growth rate, expected peak size and expected peak time of the epidemic. It is found that the theoretical best choice of allocation scheme depends on strain transmissibility, the delay in delivering antivirals under a dynamic allocation scheme and the stockpile size. A broad summary is that for realistic stockpile sizes, a dynamic allocation scheme is superior with the important exception of the epidemic final size under a severe pandemic scenario. Our results, viewed in conjunction with the practical considerations of implementing a preallocation scheme, support a focus on attempting to reduce the delay in delivering antivirals under a dynamic allocation scheme during a future pandemic.
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Antivirales/administración & dosificación , Antivirales/provisión & distribución , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Pandemias , Humanos , Gripe Humana/transmisión , Conceptos Matemáticos , Modelos Biológicos , Pandemias/estadística & datos numéricos , Procesos Estocásticos , Reserva EstratégicaRESUMEN
We develop a new methodology for the efficient computation of epidemic final size distributions for a broad class of Markovian models. We exploit a particular representation of the stochastic epidemic process to derive a method which is both computationally efficient and numerically stable. The algorithms we present are also physically transparent and so allow us to extend this method from the basic SIR model to a model with a phase-type infectious period and another with waning immunity. The underlying theory is applicable to many Markovian models where we wish to efficiently calculate hitting probabilities.
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Simulación por Computador , Epidemias , Modelos Biológicos , Enfermedades Transmisibles/transmisión , Susceptibilidad a Enfermedades , Humanos , Inmunidad , Cinética , ProbabilidadRESUMEN
Processes that spread through local contact, including outbreaks of infectious diseases, are inherently noisy, and are frequently observed to be far noisier than predicted by standard stochastic models that assume homogeneous mixing. One way to reproduce the observed levels of noise is to introduce significant individual-level heterogeneity with respect to infection processes, such that some individuals are expected to generate more secondary cases than others. Here we consider a population where individuals can be naturally aggregated into clumps (subpopulations) with stronger interaction within clumps than between them. This clumped structure induces significant increases in the noisiness of a spreading process, such as the transmission of infection, despite complete homogeneity at the individual level. Given the ubiquity of such clumped aggregations (such as homes, schools and workplaces for humans or farms for livestock) we suggest this as a plausible explanation for noisiness of many epidemic time series.
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Enfermedades Transmisibles/epidemiología , Dinámica Poblacional , Enfermedades Transmisibles/transmisión , Brotes de Enfermedades/estadística & datos numéricos , Susceptibilidad a Enfermedades/epidemiología , Epidemias/estadística & datos numéricos , Humanos , Dinámica Poblacional/estadística & datos numéricos , Procesos EstocásticosRESUMEN
Foskett Spring in Oregon's desert harbors a historically threatened population of Western Speckled Dace (Rhinichthys klamathensis). Though recently delisted, the dace's recruitment depends upon regular removal of encroaching vegetation. Previous studies assumed that Foskett Dace separated from others in the Warner Valley about 10,000 years ago, thereby framing an enigma about the population's surprising ability to persist for so long in a tiny habitat easily overrun by plants. To investigate that persistence and the effectiveness of interventions to augment population size, we assessed genetic diversity among daces inhabiting Foskett Spring, a refuge at Dace Spring, and three nearby streams. Analysis revealed a robust effective population size (Ne) of nearly 5000 within Foskett Spring, though Ne in the Dace Spring refuge is just 10% of that value. Heterozygosity is slightly lower than expected based on random mating at all five sites, indicating mild inbreeding, but not at a level of concern. These results confirm the genetic health of Foskett Dace. Unexpectedly, genetic differentiation reveals closer similarity between Foskett Dace and a newly discovered population from Nevada's Coleman Creek than between Foskett Dace and dace elsewhere in Oregon. Demographic modeling inferred Coleman Creek as the ancestral source of Foskett Dace fewer than 1000 years ago, much more recently than previously suspected and possibly coincident with the arrival of large herbivores whose grazing may have maintained open water suitable for reproduction. These results solve the enigma of persistence by greatly shortening the duration over which Foskett Dace have inhabited their isolated spring.
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Cyprinidae , Animales , Cyprinidae/genética , Ríos , Ecosistema , OregonRESUMEN
[This corrects the article DOI: 10.1016/j.lanwpc.2022.100573.].