27 research outputs found
Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster
Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In
particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and
recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations
appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating
in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally
segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are
exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we
report the results of two independent inbreeding experiments carried out with two different populations of Drosophila
melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis
among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and
mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that
synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but
also among segregating alleles in natural populationsWe acknowledge the support by Uvigo
Marine Research Centre funded by the “Excellence in Research
(INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union
through the ERDF Operational Programme Galicia 2014-2020. This
work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and
Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a
predoctoral (FPI) grant from Ministerio de Economía y
Competitividad, SpainS
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700