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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

[Admixture in commercial tetracycline preparations].

The content of admixtures in tetracycline stored under different conditions was determined with chromatographic and spectrophotometric methods. Biological activity, toxicity and colour of the drugs was tested. The changes in teh colour of tetracycline most pronounced on its storage at a temperature of 37 degrees C and elevated humidity were not accompanied by an increase in the content of anhydrotetracyclines. In parallel with the changes in the colour of tetracycline, the loss of its biological activity up to 30 per cent and increased toxicity were registered. The LD50 decreased by 40 per cent as compared to the initial level. Simultaneously an additional spot with high chromatographic mobility (Rf 0.98--1.0) was detected on thin-layer chromatograms. It was shown that the processes of tetracycline degradation resulting in marked darkening of the drug colour were not accompanied by an increase in the content of anhydro admixtures. They were probably the result of accumulation of other products which are as highly toxic and low active as the anhydroderivatives of tetracycline.

Animals

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

Ancestry, admixture, and pathogens in contemporaneous Neolithic farmers and foragers on the Island of Gotland.

Two archaeological cultural complexes; the Neolithic Funnelbeaker culture (FBC) and the Pitted ware culture (PWC), coexisted on Gotland for over 500 years, between ~3300 and 2800 calBCE. The ancestry of the FBC farmers and PWC marine foragers largely aligns with European Neolithic Farmers and European Mesolithic foragers, respectively, but the direct interactions between the groups on Gotland is not understood. We present a Middle Neolithic (MN) high-coverage genome and a Late Neolithic (LN) low-coverage genome from the Ansarve FBC dolmen. We investigate ancestry, admixture, and pathogens among these MN farmers (n = 6), foragers (n = 19), and the LN individual. We find that recent gene-flow between farmers and foragers could have taken place, although most gene-flow happened prior to their coexistence on the island. We also find evidence of different Yersinia pestis strains in the three cultural groups, showing that the pestis was widespread among groups with different subsistence strategies.

Humans

Revised standards for normal resting dead-space volume and venous admixture in men and women.

1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,O2), alveolar-to-arterial oxygen-tension difference (PAO2--Pa,O2) and venous admixture fraction (QVa/Qt) in the sitting position. 2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects. 3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,O2,(PA,O2--Pa,O2) and Qva/Qt are adequately predicted on age alone.

Adult

The AaDO2 and venous admixture at varying inspired oxygen concentrations in chronic obstructive pulmonary disease.

The alveolar to arterial oxygen pressure difference (AaDO2) and pulmonary venous admixture (Qs/Qt) were measured in 32 patients with chronic obstructive pulmonary disease during right heart catheterization at inspired oxygen concentrations (FIO2) of 21, 24, 28, 35, and 40%. Patients without chronic hypercapnia (PaCO2 is less than 45 torr, group A) had Qs/Qt less than 25% while breathing room air; their AaDO2 rose at a rate of 3 torr for each percent increase in FIO2. In those with chronic hypercapnia (PaCO2 greater than 44 torr., (group B), THE Qs/Qt was always greater than 24% during air breathing and the AaDO2 rose at a rate of 5 torr for each percentage increase in FIO2. These changes should be considered in the interpretation of the AaDO2 in patients with COPD in whom the FIO2 is changed during the course of therapy. The Qs/Qt fell curvilinearly with increasing FIO2 but the rates of fall were quantitatively different in groups A and B. A physiological explanation for the changes in Qs/Qt and ADO2 which result from changes in FIO2 is presented.

Arteries

Changes of EEG and pulmonary venous admixture during a protein load in patients with cirrhosis.

21 patients with cirrhosis of the liver and 24 control patients were studied before and after a protein load (120 g protein per day during one week). An EEG was recorded and a visual assessment of frequency pattern was performed. Venous admixture was estimated during hyperoxia. According to the EEG frequency pattern the patient group with cirrhosis was subdivided into those with EEG slowing after the protein load (n = 7) and those without (n = 14). The following results were obtained: 1) Resting arterial blood gases did not change in either group. 2) There was a significant increase of the AaD02 (difference between alveolar p02 and peripheral arterial p02) in cirrhotics and controls. 3) The increase in AaD02 was significantly larger in those cirrhotics showing EEG slowing compared to those without EEG - slowing or to the controls. 4) Fractional venous admisture increased significantly in those cirrhotics showing EEG slowing. There was no significant change in those patients who did not show EEG changes or in the controls.

Blood Pressure

Admixture Mapping Reveals Evidence for Multiple Mitonuclear Incompatibilities in Swordtail Fish Hybrids.

How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish (Xiphophorus) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridising species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.

Animals

Physicochemical determinants of incompatibility and instability in injectable drug solutions and admixtures.

Several physicochemical conditions or phenomena most commonly causing incompatibility, instability or related difficulties in parenteral drug solutions and admixtures are reviewed. The following factors involved in chemical incompatibilities are reviewed: concentration, pH, acid-base character, reduction-oxidation, photolysis, epimerization, temperature, dextrose catalysis and hydrolysis. The following factors involved in visual incompatibilities are discussed: pH, acid-base character, solvent system, color change, complexation, adsorption and adherence, dissolution rate, salting-out and leaching, and foaming. Pharmacists may recognize, predict and avoid parenteral imcompatibilities based on their experience, an understanding of physicochemical principles and reference to pertinent publications.

Chemical Phenomena

Reference aids for developing policies and procedures for intravenous admixture services.

A table of literature citations designed to help hospital pharmacists develop a policy and procedure manual for i.v. admixture services is presented. The table is categorized according to literature that will aid in developing policies and procedures for specific aspects of admixutre services (e.g., distribution procedures, quality assurance). The citations were selected from two periodicals (American Journal of Hospital Pharmacy and Drug Intelligence & Clinical Pharmacy) and three other publications.

Bibliographies as Topic

[Admixtures of antibiotic substances in enzyme preparations of microbial origin intended for use as food additives].

A group of enzymtic preparations, mainly of the Soviet make were investigated for the presence of antibiotic substances admixtures. Altogether 25 preparations obtained from molds, actinomycetes, bacteria and yeast were studied. The results showed that 18 preparations contained antibiotic substances in an amount of 0.6-1300 U, equivalent to oxytetracycline units per 1 g. Most often antibiotics were present in preparations of the pectinase and protease group. In the group of glucoamylase the antibiotic activity was uncovered in a single preparation. Procedures employed in determining the antibiotic activity of enzymatic preparations is described and the possible role of antibiotics in the manifestations of their toxic properties discussed.

Actinomycetales

[Component composition and admixtures of related compounds in commercial preparations with an erythromycin base].

Chromatographic purity of erythromycin base preparations manufactured in the USSR with various technological procedures and those of 4 foreign firms was studied. All the preparations studied in addition to the main component of erythromycin A contained 5 to 7 per cent of erythromycin C and about 1.5 to 3.5 per cent of a non-identified component possessing a somewhat lower chromatographic mobility than erythromycin C. The admixture of 0.5--1 per cent of anhydroerythmycin was found in many erythromycin preparations. The preparations of some foreign firms contained also a number of additional substances. It was shown that the antimicrobial activity of anhydroerythromycin was 50-60 times lower than that of erythromycin. Direct correla;ion between the level of the antimicrobial activity of the market prepaetions of erythromycin and the level of its chemical purity was noted.

Animals

Genomic consequences of admixture in an experimentally founded sand lizard population.

Conservation interventions are increasingly required for species threatened by population declines and isolation due to anthropogenic pressures. Small, isolated populations are particularly vulnerable to the loss of genetic diversity, increased inbreeding, and the accumulation of deleterious mutations. Translocations or supplementation of allopatric individuals for genetic rescue may be the only way to increase genetic diversity and increase population persistence via increased adaptive potential. Here, we use an experimentally admixed population of sand lizards on a small island in Sweden as a valuable model of genetic rescue. This population was established approximately 20 years ago (5-6 generations), resulting in increased fecundity and hatchling viability. This population was founded from crossings between individuals from an inbred population from the nearby mainland and individuals sourced from populations in southern Sweden. Low-coverage whole-genome sequencing revealed elevated genetic diversity and reduced realized genetic load in this admixed population relative to the source populations. Ancestry analyses indicated a greater contribution of southern Swedish genetic variation, potentially reflecting the contribution of beneficial adaptive variation from this region that may underlie the positive population effects. This system provides valuable empirical insights into the long-term genomic consequences of genetic rescue in this model vertebrate population.

Journal Article