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Compounding times and contamination rates associated with the preparation of intravenous admixtures in three types of plastic containers.

The compounding times and contamination rates associated with the preparation of admixtures in three different plastic i.v. containers of dextrose 5% in water were compared. The time required for a technician to prepare, in a laminar air flow hood by the needle and syringe technique, 120 admixtures in each of three different plastic i.v. containers was measured and recorded by two investigators. The 360 admixtures were tested within one hour of preparation for sterility using an enriched brain heart infusion broth. The total time required to compound the i.v. admixtures varied significantly with container design (p less than 0.01), preparation being fastest with the Accumed container, followed by the LifeCare then the Viaflex containers. The major contributing factors to increased compounding time were (1) removal of outer wrap, (2) swabbing of LifeCare and Viaflex medication ports with isopropyl alcohol pads and (3) freeing of the hangar flap from the Viaflex container. Sterility tests revealed no detectable contamination of any of the admixtures. Container design of plastic i.v. containers did influence the preparation time for admixtures but did not influence admixture sterility.

Drug Combinations

Adventitious contamination of intravenous admixtures during sterility testing.

The extent to which contamination of intravenous fluids measured by inhospital sterility-testing may be due to adventitious contamination (i.e., contamination introduced during the sterility-testing procedure) was studied. All one-liter admixtures prepared during a three-day period in a busy centralized i.v. admixture service were studied. Samples of i.v. admixtures were cultured before and after administration by direct ioculation or by culturing the membrane through which the admixture was filtered. Samples of similarly cultured large-volume parenterals served as controls. Contamination rates for control and admixture samples were not significantly different (p = 0.23). Of 10 control and test (admixture) solutions showing contamination before administration, only one test solution again showed contamination after administration but this was with a different microbe. The results suggest that adventitious contamination during sampling/culturing procedures is a component of, and possibly a dominant factor in, the contamination rates detected by inhospital sterility tests. Combined with infection surveillance, sterility tests may be of value when infections are possibly related to admixture contamination.

Bacteria

Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 1: stability with common intravenous fluids.

The stability of dopamine hydrochloride (Intropin) in several large-volume parenteral solutions was studied. Admixtures of dopamine were assayed by colorimetric and chromatographic procedures. Admixtures (800 mug dopamine per ml) in the following intravenous fluids in glass bottles at pH 6.85 or below were found to be chemically and physically stable for at least 48 hours at room temperature: dextrose 5%, dextrose 5% and sodium chloride 0.9%, 5% dextrose in 0.45% sodium chloride, dextrose 5% in lactated Ringer's solution, lactated Ringer's injection, 0.9% sodium chloride, 1/6 molar sodium lactate, and 20% mannitol. The admixture of dopamine in 5% dextrose was stable for a minimum of seven days at 5 C. A 5% dextrose-dopamine admixture in a polyvinylchloride bag was stable for at least 24 hours at room temperature. The admixture of dopamine in 5% sodium bicarbonate solution produced an unstable solution of pH 8.20. A chemical and physical change (development of a pink color) was observed in this admixture. It is recommended that dopamine not be added to 5% sodium bicarbonate solution or any alkaline intravenous solution.

Chemical Phenomena

Assuring the quality of intravenous admixture programs.

Several aspects of quality assurance (QA) methods in i.v. admixture programs are discussed, and a basic framework for developing QA programs for admixture services is presented. The objective of QA is to insure that admixture products: (1) are therapeutically and pharmaceutically appropriate to the patient; (2) are free from microbial and pyrogenic contaminants; (3) are free from undesirable levels of particulate or toxic contaminants; (4) contain drugs in correct amounts; and (5) are labeled, stored and distributed under principles of good drug control. Three types of QA criteria bases which may be used as indicators of quality are discussed (resources, facilities and organization; required procedures; end-products or results). Because end-product monitoring has certain limitations in the admixture setting, QA must rely heavily on procedure-centered review methods. General guidelines for developing QA programs are outlined. Adherence to procedure is the key to assuring the quality of admixture products. In developing a QA program, the highest priority should be given to the education and training of admixture personnel, particularly with respect to aseptic technique and pharmaceutical calculations.

Drug Combinations

Nested Admixture During and After the Trans-Atlantic Slave Trade on the Island of São Tomé.

Human genetic admixture, involving the contact between two or more previously isolated populations, can be a complex process influenced by social dynamics. In this study, we aim to reconstruct complex admixture histories in São Tomé, an island in the Gulf of Guinea where the Portuguese established one of the first plantation-based slave societies. Since the 15th century, migration waves from Africa and Europe, slavery, marooning, and indentured labour led to profound demographic shifts and social stratification on the island. Examining 2.5 million SNPs newly genotyped in 96 São Toméans, we observed patterns of genetic differentiation that were more complex than those of other populations descended from enslaved Africans on either side of the Atlantic. Using local ancestry inference and Identical-by-Descent methods, we identified five genetic clusters in São Tomé and reconstructed shared ancestries between each cluster and 70 African and European population samples, including an extensive sample from the Cabo Verde archipelago. Our findings align with historical records, retracing the major slave trade routes and labour-driven migrations after the abolition of slavery. We also identified gene flow between recently admixed groups that were previously isolated on the island. We call this process, creating multiple layers of genetic ancestry in admixed genomes, nested admixture. We suggest that changing social structures in São Tomé transformed the genetic structure of its population and influenced the admixture process. This study demonstrates how successive admixture and isolation events during and after the Trans-Atlantic Slave Trade shaped extant genetic diversity patterns at local scale in Africa.

Humans

Statistical test to compare the linkage model and the admixture model based on central limit results.

In the Admixture Model, the probability that an individual carries a certain allele at a specific marker depends on the allele frequencies in K ancestral populations and the proportion of the individual's genome originating from these populations. The markers are assumed to be independent. The Linkage Model is a Hidden Markov Model that extends the Admixture Model by incorporating linkage between neighboring loci. We prove consistency and asymptotic normality of maximum likelihood estimators for the ancestry of individuals in the Linkage Model, complementing earlier results by (Pfaff et al., 2004; Pfaffelhuber and Rohde, 2022; Heinzel, 2025) for the Admixture Model. These results are used to prove that a statistical test that allows for model selection between the Admixture Model and the Linkage Model is an asymptotic level-α-test. Finally, we demonstrate the practical relevance of our results by applying the test to real-world data from The 1000 Genomes Project Consortium (2015).

Genetic Linkage

Sex-Biased Admixture Followed by Isolation and Adaptive Evolution Shaped the Genomic and Blood Pressure Diversity of the LopNur People.

The LopNur people are an ethnic group living on the edge of the Taklamakan Desert, and they are believed to demonstrate a unique genetic makeup due to their isolation and limited contact with neighboring populations. However, a lack of genetic studies on the LopNur people has resulted in limited knowledge about their ancestral origins and demographic history. Here, we conducted the first whole-genome sequencing study of 164 LopNur individuals (LOP) to gain insight into their genetic history and adaptive evolution in an isolated desert area. Our analysis revealed that the present-day LOP have experienced a complex history of admixture followed by long-term isolation, with their ancestry derived from East Asia (∼41.46%), West Eurasia (∼26.43%), Siberia (∼24.27%), and South Asia (∼7.82%). Notably, a remarkable sex-biased admixture occurred between Western males and Eastern females. In addition to complex admixture followed by long-term geographic isolation and further recent migrations, adaptive evolution jointly formed the gene pool and phenotypic diversity of the present-day LOP. Intriguingly, our analysis suggests that the USP35-GAB2 region may be correlated with blood pressure in LOP, based on a joint analysis of genomics and blood pressure data. Moreover, we identified two variants, rs7387065, and rs2229437, located on CSMD1 and PRCP, respectively. These variants exhibited frequency differences between Asian and European populations and were reported to be associated with antihypertensive drug absorption. Our results provide new insight into the complex history of the LOP, an admixed and isolated ethnic group residing at the crossroads of East and West, a case with ancient admixture, long-term isolation, adaptive evolution, and sex-biased gene flow.

Female

Deciphering the mosaic genome of sugarcane cultivars through polyploid admixture inference with AdmixPoly.

BACKGROUND: Characterizing population structure and admixture events between ancestral groups plays a key role in understanding the evolutionary history of species and crops. Most tools for inferring admixture have been developed for diploids and are not suitable for polyploids, in particular those with high and mixed ploidy such as Saccharum. RESULTS: Here we present AdmixPoly, an R-package designed to infer admixture in polyploid species both at the genome-wide scale and locally along chromosomes. We compare AdmixPoly with state-of-the-art methods using simulations, demonstrating its precision and computational efficiency. Notably, local admixture inference in complex scenarios, such as high ploidy levels, large numbers of ancestral groups and alleles per marker is enabled through efficient approximations of emission and transition probabilities within a hidden Markov model framework. We apply this approach to characterize the contributions of wild Saccharum species to the complex polyploid genome of modern sugarcane cultivars. A panel of wild and cultivated Saccharum accessions is genotyped for 80K genomic regions, each revealing approximately 50 read-scale haplotypes. CONCLUSIONS: The results reveal that most of the approximately 12 copies of each basic chromosome in modern cultivars are derived from the domesticated species Saccharum officinarum, with one to four copies typically contributed by distinct subgroups of the wild species Saccharum spontaneum. In addition, contributions from an unknown wild Saccharum group originating from the Pacific were identified in most cultivars. The conserved pattern of these introgressions suggests that they can be traced back to the early stages of sugarcane breeding approximately a century ago.

Saccharum

Post-colonial human admixture and natural selection: disentangling signals in complex demographic contexts.

Natural selection and admixture are defining population genetic features of modern human populations, yet their interaction has only recently emerged as a major focus in human evolutionary genomics. While the influence of natural selection on population structure and trait diversity is well established, the ways in which selective pressures operate after admixture have historically received far less attention. In this review, we synthesise the latest progress in understanding post-admixture selection and highlight case studies that illustrate how novel environments, pathogen exposure, dietary shifts and socio-historical transformations have driven genomic adaptation. We conclude by identifying key gaps that remain in the field with the aim of motivating future research and facilitating new insights into how admixture and selection jointly shape human diversity.

Journal Article

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have largely been understudied in medical research due to their complex genetic ancestries. However, the consideration of admixture can help identify ancestry-enriched genetic associations, delineating some of the genetic underpinnings of cross-population phenotypic variation. To this end, we performed local ancestry inference within the All of Us Research Program to identify individuals with recent admixture between African (AFR) and European (EUR) populations (N=48,921). We identified evidence of local AFR ancestry enrichment at the HLA locus, suggestive of putative selection since admixture. Furthermore, we performed the largest admixture mapping (ADM) efforts in AFR-EUR Admixed individuals for 22 traits, identifying 71 associations between inferred local AFR ancestries and a trait. Variants from published GWAS could only account for 18 (25%) of the ADM associations, highlighting novel loci where ancestral haplotypes explained some phenotypic variation. Previous studies likely have not identified these loci due to the low availability of high-powered GWAS in populations genetically similar to AFR. One such loci was 9q21.33, associated with 1.4-fold risk of end-stage kidney disease (ESKD) for carriers of inferred local AFR ancestries at the region. This locus contains the gene SLC28A3, which has previously been linked to kidney function but has never been associated with cross-population ESKD prevalence differences. Together, our results expand upon the existing literature on phenotypic differences between populations, highlighting loci where genetic ancestries play a critical role in the genetic architecture of disease.

Journal Article

Admixture-mapping analysis reveals genetic determinants of the human plasma proteome.

Protein profiling and genetic findings can be integrated to define the genetic architecture of the circulating proteome in chronic diseases. Most self-identified African American (AA) individuals have both African and European genetic ancestry. Admixture mapping can detect genomic association regions in which causal variants exist with substantial differences in allele frequency or effect sizes between genetic ancestries. We performed admixture mapping of the circulating proteome in 1,989 participants from the Jackson Heart Study (JHS), investigating the relation of local African ancestry within genomic regions with levels of circulating proteins. We conditioned protein-local ancestry association models on variants previously found to be associated with those proteins in genome-wide association studies (GWASs). We replicated findings in 196 AA participants from the Multi-Ethnic Study of Atherosclerosis (MESA). 62 proteins were associated with local African ancestry. 21 of 62 remained statistically significant after conditioning on protein-associated variants observed in previous GWASs. 48 of 54 available protein-local ancestry associations were replicated in the MESA. Proteins associated with local African ancestry included chemokines, factors associated with vascular biology and inflammation, and other biologically interesting proteins. Admixture associations unexplained by previously reported protein-associated variants in conditional analysis suggest the existence of causal variants missed by standard GWAS techniques.

Aged

Peruvian Population Genomics: Unraveling the Genetic Landscape and Admixture Dynamics of Urban Populations.

Latin American populations exhibit high genetic and phenotypic diversity shaped by complex admixture histories, yet remain underrepresented in genomic research. Here, we analyze genome-wide data from 432 urban individuals across 13 regions of Peru, including 346 newly genotyped from the Peruvian Genome Project. We revealed fine-scale population structure and demographic patterns shaped by both ancient and recent events. Indigenous American ancestries in urban individuals trace back to ancient north-south interactions consisted with archaeological records, while admixture events occurring within the last 8-10 generations involved sources already admixed between distinct ancestral lineages. Identity-by-descent analyses reveal sustained gene flow in southern Peru, while effective population size trends highlight demographic stability in Lima over the past 25 generations. Sex-biased admixture patterns suggest Indigenous ancestry contribution preferentially mediated by females. These findings offer a comprehensive view of Peru's genetic heritage, advancing our understanding of human genetic diversity and historical demographic processes in Latin America.

Admixture

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N = 48,921). Across 22 traits, we identified 71 ancestry-trait associations, including loci where ancestral haplotypes explained phenotypic variation yet were missed by single-variant association testing due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries are associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in explaining differences between populations. Together, our results expand upon the phenotypic differences between populations and characterize loci where genetic ancestries play a critical role in the architecture of disease.

Humans

Venous admixture in human septic shock: comparative effects of blood volume expansion, dopamine infusion and isoproterenol infusion on mismatching of ventilation and pulmonary blood flow in peritonitis.

A hemodynamic study with blood gas analysis was performed so we could observe changes induced by blood volume expansion, dopamine infusion and isoproterenol infusion in 20 adult patients suffering from peritonitis complicated with septic shock and acute respiratory failure. Blood volume expansion increased cardiac index (from 2.6 +/- 1.21/min/m2 to 3.4 +/- 1.31/min/m2; p less than 0.001), but also enhanced venous admixture (QS/QT) from 27 +/- 14% to 36 +/- 13%; p less than 0.01). Dopamine infusion increased cardiac index (from 2.6 +/- 0.9 1/min/m2 to 3.4 +/- 1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 25 +/- 11% to 31 +/- 12%, p less than 0.001). Isoproterenol infusion increased cardiac index (from 2.6 +/- 0.9 l/min/m2 to 3.6 +/- 1.1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 27 +/- 12% to 33 +/- 11%; p less than 0.001). This worsening in mismatching of ventilation and blood flow is correlated with the enhancement in pulmonary blood flow obtained by these three therapeutic procedures.

Adult

Admixture and Selection Driven by El Niño-Southern Oscillation Events Shape the Genetic Structure of Octopus mimus-O. hubbsorum Complex Across the Humboldt and South Equatorial Current Transition Zone.

Marine transition zones, where contrasting water masses converge, can function as natural laboratories for studying admixture and early stages of speciation. The genomic structure of the eastern Pacific Octopus mimus-O. hubbsorum complex was investigated by analyzing whole-genome sequencing data from 67 individuals sampled along the west coast of the Americas, spanning Mexico and the Peruvian coast. This includes the South Equatorial Current, the transition zone, and the Humboldt Current System. The mitochondrial genomes fell into two major genetic clades that largely corresponded to the warm-water northern (O. hubbsorum) and cold-water southern (O. mimus) lineages. Analyses of the nuclear genomes revealed the same bipartite structure but also identified a broad admixture zone characterized by two different admixed clades (Admixed-Cold and Admixed-Warm). The results suggest that episodic relaxation of oceanographic barriers during El Niño-Southern Oscillation (ENSO) events promotes secondary contact and gene flow, resulting in admixed individuals recurrently during ENSO years. However, the survival of these admixed individuals depends on the adaptive genetic composition of each organism and the prevailing environmental conditions. Outlier SNP analysis supports these findings, where the Admixed-Cold cluster shares mainly the adaptive genetic component identified as outliers in O. mimus, while Admixed-Warm is linked to those in O. hubbsorum. The O. mimus-O. hubbsorum complex is currently occupying a gray zone of speciation, in which selection and climate-driven connectivity act in tandem to shape genomic divergence.

gene flow

HAP-SAMPLE2: data-based resampling for association studies with admixture.

MOTIVATION: HAP-SAMPLE2 extends the functionality of the original HAP-SAMPLE tool for simulating genotype-phenotype data, now with features to handle population admixture and rare variant analysis. It allows users to define parameters such as disease prevalence and allele effect sizes for both common and rare variant simulations. RESULTS: HAP-SAMPLE2 provides an efficient means for simulating complex datasets, suitable for large-scale projects like the 1000 Genomes Project. Its capabilities for population admixture allow users to create admixed populations or preserve substructures while introducing novel variation through artificial recombination. Additionally, the tool supports burden testing for rare variants using fixed and Madsen-Browning weighting schemes. AVAILABILITY AND IMPLEMENTATION: The software, along with a detailed vignette, is available on GitHub: https://github.com/M3dical/HAPSAMPLE2.

Software

Evaluation of compounding accuracy and aseptic techniques for intravenous admixtures.

Intravenous admixtures containing potassium collected from three hospital pharmacies were analyzed for compounding accuracy, sterility and pyrogenicity. The study was performed in two stages. During stage I, pharmacists and technicians were not informed of the study, but during stage II they were informed. In each stage 10 samples were collected from each person in the two personnel groups, analyzed and the results compared between the two personnel groups and the two stages. Results of the study showed that without monitoring (stage I) pharmacists had a higher mean percent error and contamination level than technicians. With monitoring, however, pharmacists showed a lower mean percent error and contamination level than technicians. Both personnel groups showed a decline in their mean percent error in the second stage, but there were still 83 (39.5%) errors in compounding accuracy greater than +/- 6%. No positive results with the Limulus test for pyrogens were obtained. It is recommended that a planned program of quality control be instituted for the preparation of i.v. admixtures by both pharmacists and technicians.

Antisepsis

Gm allotypes and racial admixture in two Brazilian populations.

The Gm types of 515 inhabitants of Belém and 395 inhabitants of Porto Alegre, Brazil were studied in an attempt to quantitatively estimate ethnic parental contributions. The people from Belém can be characterized as 24% black, 22% Indian, and 54% Caucasian. The Porto Alegre blacks seem to have inherited as much as 53% of their genes from Caucasian ancestors, while the whites living there have inherited 8% of their genes from African ancestors. The admixture values obtained for Belém are very similar if just the Gm system is considered or it plus seven other loci are considered, emphasizing the high efficiency of the Gm markers in such analyses.

Adult