The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa.Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations.Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

Source and spread dynamics of mountain pine beetle in central Alberta, Canada

The mountain pine beetle (Dendroctonus ponderosae Hopkins) (Coleoptera: Curculionidae) is a significant destructive force in the pine forests of western Canada and has the capacity to spread east into a novel host tree species, jack pine (Pinaceae). New populations have been documented in central Alberta, Canada, but the source populations for these outbreaks have yet to be identified. In this study, we use genetic data to identify parent populations for recent outbreak sites near Slave Lake, Lac La Biche, and Hinton, Alberta. We found the northern population cluster that entered Alberta near Grande Prairie was the source of the most eastern established population near Lac La Biche, and the range expansion to this leading-edge population has been too rapid to establish evidence of population structure. However, some dispersal from a population in the Jasper and Hinton area has been detected as far north and east as Slave Lake, Alberta. We also identified two potential source populations for the current outbreak in Hinton: most beetles appear to be from Jasper National Park, Alberta, but some also originated from the northern population cluster. These findings demonstrate the dynamic dispersal capabilities of mountain pine beetle across the Alberta landscape and the potential hazard of increased dispersal to newly established leading-edge populations.

Kebijakan Pemerintah Mengenai Coronavirus Disease (COVID-19) di Setiap Provinsi di Indonesia Berdasarkan Analisis Klaster

Coronavirus disease (COVID-19) is a disease that was only discovered in 2019 and has been reported to have spread to almost all over the world. This pandemic has caused anxiety and fear for all Indonesians because it can be transmitted easily through humans. This study aims to cluster each province in Indonesia into certain clusters so that they can find out the characteristics, movements, and government policies that must be carried out in each cluster. This study uses secondary data regarding COVID-19 cases in Indonesia, which reached 4800 data from March 1 to August 11, 2020, in 34 Indonesian provinces. The four variables used were the number of cases of death, the number of cured cases, the number of active cases, and the number of deaths per one million population. Cluster 1 has a high risk because it has the highest variable number of active cases and the number of deaths per one million population. Cluster 2 has a low risk because it has a variable with the highest number of cured cases and the lowest number of active cases. Cluster 3 has a moderate risk because it has the lowest number of cures variable and the moderate number of active cases. The government policy in cluster 1 should prioritize the variable number of active cases and the number of death cases per one million population, cluster 2 must prioritize the variable number of deaths, and cluster 3 must prioritize the variable number of active cases.

Race, Definition, and Science

Philosophical concerns about the reality of race often depend on the examination of our ordinary race concepts, and whether the biological sciences might support the existence of those concepts. We can approach these philosophical concerns by looking at how we might define a race concept from both ordinary discourse (the folk definition), and from the viewpoint of the biological sciences (as a subspecies or population cluster). After noting the difficulties with giving a satisfactory definition of race in both domains, we can see more clearly why our race concepts cannot claim any obvious support from the biological sciences.

The Role of Sample Cluster Means in Multilevel Models

The paper explores some issues related to endogeneity in multilevel models, focusing on the case where the random effects are correlated with a level 1 covariate in a linear random intercept model. We consider two basic specifications, without and with the sample cluster mean. It is generally acknowledged that the omission of the cluster mean may cause omitted-variable bias. However, it is often neglected that the inclusion of the sample cluster mean in place of the population cluster mean entails a measurement error that yields biased estimators for both the slopes and the variance components. In particular, the contextual effect is attenuated, while the level 2 variance is inflated. We derive explicit formulae for measurement error biases that allow us to implement simple post-estimation corrections based on the reliability of the covariate. In the first part of the paper, the issue is tackled in a standard framework where the population cluster mean is treated as a latent variable. Later we consider a different framework arising when sampling from clusters of finite size, where the latent variable methods may have a poor performance, and we show how to effectively modify the measurement error correction. The theoretical analysis is supplemented with a simulation study and a discussion of the implications for effectiveness evaluation.

Cannibals, Warriors, Conquerors, and Colonizers: Western Perceptions and Azande Historiography

Mainly as a result of the work of E. E. Evans-Pritchard, the Azande are among the best-known African peoples. In anthropological theory they have become indissolubly associated with the study of religion and magic. Also remarkable is their expansion under the leadership of the dynasties of the Avungara and the originally Ngbandi-speaking Abandia. Starting from a small core area in the basin of the lower Mbomu, where the ancestors of the Avungara and Abandia had established themselves as rulers over parts of the resident, mainly Zande-speaking, population around the middle of the eighteenth century, the Abandia extended their rule into the region of the lower Mbomu and lower Uele, while the Avungara and their Azande followers swept eastward in a vast movement and in less than one hundred years conquered a huge area reaching as far as the upper Sue and upper Uele, integrating the population into their system of rule.One of the reasons for the speed of this expansion is that individual members of the Avungara dynasty (who all claimed descent from Ngura, the first historical ruler in the lower Mbomu area) repeatedly founded principalities of their own in new territories. This led to the existence of a varying number of polities under numerous, more or less, powerful rulers who descended from several dynastic branches, thereby preventing the formation of a single kingdom, stable in time and place. Through the integration of numerous groups of different linguistic and ethnic origins, the population cluster was formed for which the collective name Azande has become established. The history of Azande expansion thus provides a very interesting example of a society being created through political processes, which raises questions concerning the origin, acceptance, and characteristics of centralized political organizations, as well as assimilation and acculturation processes (besides the Mangbetu in the Uele-Bomokandi area, the Azande were the only group in the region to develop centralized political structures on a wide scale).