Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

TRY plant trait database - enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Parâmetros genéticos para características de crescimento e reprodutivas em bovinos Nelore no Brasil

To know the genetic and phenotypic progress of a population is important to evaluate the outcome of the adopted selection programmes and as guiding elements of future actions. The objective was to estimate genetic parameters, genetic and phenotypic trends of weights at 205 (W205) 365 (W365) 550 (W550) days of age, age at first calving (AFC), scrotal circumference (SC) and calving interval (CI) of 175.231 Nellore, born in the period 1967-2011 in the Northeast region of Brazil. The components of (co) variance and breeding values were obtained by restricted maximum likeli-hood methodology. Estimates of heritability coefficients for growth traits were of a low to moderate magnitude. Direct selection will provide greater genetic gains for W550. For reproductive traits, the heritability estimate was low for ACF and close to zero for CI. However, for the SC heritability was moderate, indicating its use as selection criteria. Direct genetic trends for W205, W365, W550 and ACF indicate small genetic gains over the years. Phenotypic progress shows that the features are improving with the years, mainly because of environmental improvements.Conhecer o progresso genético e fenotípico de uma população é importante para se avaliar o resultado dos programas de seleção adotados e como elementos norteadores de ações futuras. Assim, objetivou-se estimar parâmetros genéticos, tendências genéticas e fenotípicas dos pesos aos 205 (P205), 365 (P365) e 550 (P550) dias de idade, idade ao primeiro parto (IPP), circunferência escrotal (CE) e intervalos de partos (IDP) de 175.231 bovinos Nelore, nascidos no período de 1967 a 2011 na região Nordeste do Brasil. Os componentes de (co) variância e valores genéticos foram obtidos por meio da metodologia da máxima verossimilhança restrita. As estimativas dos coeficientes de herdabilidades para as características de crescimento foram de baixa a moderada magnitude. A seleção direta proporcionará maiores ganhos genéticos para P550. Para as características reprodutivas, a estimativa de herdabilidade foi baixa para IPP e próxima a zero para IDP. Contudo, para a CE a herdabilidade foi moderada, indicando seu uso como critério de seleção. As tendências genéticas diretas para P205, P365, P550 e IPP, indicam pequenos ganhos genéticos ao longo dos anos. Os progressos fenotípicos evidenciam que as características estão melhorando com o decorrer dos anos, principalmente em decorrência da melhoria ambiental

Parameters and genetic trends for reproductive characteristics of a closed Angus herd

Abstract Background: Closed breeding populations are useful to conduct basic and applied research. The Wye Angus herd is one of them. It was founded using only a few animals. The pedigree of the descendants of the original herd can be completely described by historical records resulting from strong selection. Wye Angus genetics has influenced that of Aberdeen Angus, Red Angus, and Brangus cattle worldwide. Objective: To evaluate parameters and genetic trends associated with the reproduction traits of the Wye Angus herd between the years 1937 and 2012. Methods: We used pedigree information of 11,692 individuals. The reproductive traits assessed were age at first calving (AFC), calving interval (CI), and scrotal circumference (SC). The covariance components were estimated by Bayesian inference. The genetic trends were obtained by linear regression of the genetic values over birth years of the animals. Results: The heritability estimates for AFC, and CI were negligible, although a small genetic gain was associated with CI. Because the AFC and CI values of the herd are small, past reproductive management has produced favourable results for the heifers. Conclusion: The Wye Angus herd has enough genetic variability for genetic gain through selection on SC.Resumo Antecedentes: O rebanho Wye Angus foi fundado a partir de poucos animais e destaca-se por ser um rebanho fechado, com informações completas de pedigree e forte seleção, oferecendo vantagens únicas em termos de realização de pesquisas em melhoramento genético animal. Além disso, a genética de Wye Angus tem influenciado os de Aberdeen Angus, Red Angus e Brangus em todo o mundo. Objetivo: Avaliar os parâmetros genéticos e tendências de características reprodutivas do rebanho Wye Angus no período entre 1937 e 2012. Métodos: Foram usadas informações do pedigree de 11.692 individuos. As características avaliadas foram: perímetro escrotal (SC), idade ao primeiro parto (AFC), e do intervalo entre partos (CI). Componentes de (co) variância foram obtidos por meio da metodologia Bayesiana. As tendências genéticas foram obtidas por regressão linear ponderada dos valores genéticos sobre o ano de nascimento do animal. Resultados: Hereditariedade para AFC e CI foram insignificantes, embora um pequeno ganho genético tenha sido associado a CI. No entanto, os valores para AFC e CI do rebanho são baixos, indicando que o manejo reprodutivo trouxe resultados favoráveis para as novilhas. Conclusão: O rebanho Wye Angus tem variabilidade genética suficiente para ganho genético através de seleção para SC.Resumen Antecedentes: Las poblaciones reproductivas cerradas son útiles para realizar investigacion básica y aplicada. El hato Wye Angus es uno de ellos. Fue fundado utilizando sólo unos pocos animales. El pedigrí de los descendientes del hato original puede describirse completamente mediante registros históricos resultantes de una fuerte selección. La genética del Wye Angus ha influido en la del Aberdeen Angus, Red Angus y Brangus en todo el mundo. Objetivo: Evaluar los parámetros y las tendencias genéticas de características reproductivas del rebaño Wye Angus en el periodo entre 1937 y 2012. Métodos: Utilizamos información de pedigrí de 11.692 individuos. Las características evaluadas fueron circunferencia escrotal (SC), edad al primer parto (AFC) y el intervalo entre partos (CI). Los componentes de (co)variancia fueron obtenidos mediante metodología Bayesiana. Las tendencias genéticas fueron obtenidas por regresión lineal ponderada de los valores genéticos sobre el año de nacimiento del animal. Resultados: Las estimaciones de heredabilidad para AFC y CI fueron insignificantes, aunque se asoció un pequeño beneficio genético con CI. Sin embargo, la AFC y el CI del rebaño son bajos, indicando que el manejo reproductivo ha traído resultados favorables para las novillas. Conclusion: El rebaño Wye Angus posee suficiente variabilidad genética para la ganancia genética por medio de la selección para SC

Genetic and environmental effects on parturition and lactation intervals in water buffaloes from Brazil

Genetic and environmental effects on parturition interval (PI) and duration of lactation (DL) were evaluated in 107 Jafarabadi, 98 Mediterranean, 1027 Murrah and 624 crossbred buffalo females (n=1856), based on data from the Buffalo Genetic Improvement Program-PROMEBUL from 1980 to 2003. The statistical model included effects of herd, parturition year and month, calf's sex, parturition order and genetic group, composing 11, 34, 12, 2, 12 and 4 classes, respectively. A significant effect over PI was observed (P<0.01) in all classes, excepting sex. Mean parturition intervals per genetic group presented significant differences through SNK test (P<0.05), with mean values of 451.29; 429.47; 406.97 and 389.78 days in Mediterranean, crossbred, Murrah and Jafarabadi, respectively. Mean DL values were 276.68; 270.33; 258.03 and 235.59 days for Mediterranean, Murrah, crossbred and Jafarabadi groups, respectively. No significant differences in DL were observed in relation to genetic groups. However, herd and parturition order, year and month significantly influenced DL (P<0.01). The herd was the main source of variation over DL, followed by parturition year and month. A regression based on parturition month in relation to PI and DL showed that females giving birth in the last months of the year presented higher PI and DL