Genetic load and extinction in peripheral populations: the roles of migration, drift and demographic stochasticity

We analyse how migration from a large mainland influences genetic load and population numbers on an island, in a scenario where fitness-affecting variants are unconditionally deleterious, and where numbers declines with increasing load. Our analysis shows that migration can have qualitatively different effects, depending on the total mutation target and fitness effects of deleterious variants. In particular, we find that populations exhibit a genetic Allee effect across a wide range of parameter combinations, when variants are partially recessive, cycling between low-load (large-population) and high-load (sink) states. Migration further reduces load in the sink state (by increasing heterozygosity) but increases load in the large-population state (by hindering purging). We identify various critical parameter thresholds at which one or other stable state collapses, and discuss how these thresholds are influenced by the genetic vs. demographic effects of migration. Our analysis is based on a 'semi-deterministic' analysis, which accounts for genetic drift but neglects demographic stochasticity. We also compare against simulations which account for both demographic stochasticity and drift. Our results clarify the importance of gene flow as a key determinant of extinction risk in peripheral populations, even in the absence of ecological gradients.

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Population fragmentation causes inadequate gene flow and increases extinction risk

10.1093/oso/9780198783398.003.0005 ◽

2017 ◽

Author(s):

Richard Frankham ◽

Jonathan D. Ballou ◽

Katherine Ralls ◽

Mark D. B. Eldridge ◽

Michele R. Dudash ◽

...

Keyword(s):

Gene Flow ◽

Extinction Risk ◽

Random Mating ◽

Large Population ◽

Isolated Population ◽

Population Fragmentation ◽

Single Population ◽

Total Size ◽

Limited Gene Flow

Most species now have fragmented distributions, often with adverse genetic consequences. The genetic impacts of population fragmentation depend critically upon gene flow among fragments and their effective sizes. Fragmentation with cessation of gene flow is highly harmful in the long term, leading to greater inbreeding, increased loss of genetic diversity, decreased likelihood of evolutionary adaptation and elevated extinction risk, when compared to a single population of the same total size. The consequences of fragmentation with limited gene flow typically lie between those for a large population with random mating and isolated population fragments with no gene flow.

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Planetary Nebulae in M31: Abundances, and comparison with bright Planetary Nebulae in the LMC

Symposium - International Astronomical Union ◽

10.1017/s007418090013178x ◽

1997 ◽

Vol 180 ◽

pp. 475-476

Author(s):

M. G. Richer ◽

G. Stasińska ◽

M. L. McCall

Keyword(s):

Planetary Nebula ◽

Luminosity Function ◽

Large Population ◽

Wavelength Region ◽

Planetary Nebulae ◽

Surprising Result ◽

Population Synthesis ◽

Abundance Distribution ◽

Wide Range ◽

The Mean

We have obtained spectra of 28 planetary nebulae in the bulge of M31 using the MOS spectrograph at the Canada-France-Hawaii Telescope. Typically, we observed the [O II] λ3727 to He I λ5876 wavelength region at a resolution of approximately 1.6 å/pixel. For 19 of the 21 planetary nebulae whose [OIII]λ5007 luminosities are within 1 mag of the peak of the planetary nebula luminosity function, our oxygen abundances are based upon a measured [OIII]λ4363 intensity, so they are based upon a measured electron temperature. The oxygen abundances cover a wide range, 7.85 dex < 12 + log(O/H) < 9.09 dex, but the mean abundance is surprisingly low, 12 + log(O/H)–8.64 ± 0.32 dex, i.e., roughly half the solar value (Anders & Grevesse 1989). The distribution of oxygen abundances is shown in Figure 1, where the ordinate indicates the number of planetary nebulae with abundances within ±0.1 dex of any point on the x-axis. The dashed line indicates the mean abundance, and the dotted lines indicate the ±1 σ points. The shape of this abundance distribution seems to indicate that the bulge of M31 does not contain a large population of bright, oxygen-rich planetary nebulae. This is a surprising result, for various population synthesis studies (e.g., Bica et al. 1990) have found a mean stellar metallicity approximately 0.2 dex above solar. This 0.5 dex discrepancy leads one to question whether the mean stellar metallicity is as high as the population synthesis results indicate or if such metal-rich stars produce bright planetary nebulae at all. This could be a clue concerning the mechanism responsible for the variation in the number of bright planetary nebulae observed per unit luminosity in different galaxies (e.g., Hui et al. 1993).

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A high-throughput and sensitive methodology for the quantification of urinary 8-hydroxy-2′-deoxyguanosine: measurement with gas chromatography-mass spectrometry after single solid-phase extraction

Biochemical Journal ◽

10.1042/bj20040004 ◽

2004 ◽

Vol 380 (2) ◽

pp. 541-548 ◽

Cited By ~ 78

Author(s):

Hai-Shu LIN ◽

Andrew M. JENNER ◽

Choon Nam ONG ◽

Shan Hong HUANG ◽

Matthew WHITEMAN ◽

...

Keyword(s):

Gas Chromatography ◽

Solid Phase Extraction ◽

Healthy Subjects ◽

Solid Phase ◽

Large Population ◽

Urine Samples ◽

Gas Chromatography Mass Spectrometry ◽

Phase Extraction ◽

Freeze Dried ◽

Wide Range

8-Hydroxy-2´-deoxyguanosine (8OHdG) is a widely used biomarker for the measurement of endogenous oxidative DNA damage. A sensitive method for the quantification of 8OHdG in urine by single solid-phase extraction and GC-MS (gas chromatography with MS detection) using selective ion monitoring is described in the present study. After solid-phase extraction, samples are freeze-dried, derivatized by trimethylsilylation and analysed by GC-MS. The urinary 8OHdG was quantified using heavy isotope dilution with [18O]8OHdG. The recovery of 8OHdG after the solid-phase extraction ranged from 70 to 80% for a wide range of urinary 8OHdG levels. Using 1 ml of urine, the limit of quantification was >2.5 nM (2.5 pmol/ml) and the calibration curve was linear in the range 2.5–200 nM. This method was applied to measure 8OHdG in urine samples from 12 healthy subjects. The intra- and inter-day variations were <9%. Urinary 8OHdG levels in spot urine samples from four healthy subjects were also measured for 1 week and, again, the variation was small. The presence of H2O2 in urine did not cause artifactual formation of 8OHdG. Since this assay is simple, rapid, sensitive and reproducible, it seems suitable to be used as a routine methodology for the measurement of urinary excretion of 8OHdG in large population studies.

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Pregnancy Experience after Delivery of a Child with a Major Birth Defect: A Population Study

PEDIATRICS ◽

10.1542/peds.95.1.59 ◽

1995 ◽

Vol 95 (1) ◽

pp. 59-65

Author(s):

Margarett K. Davis ◽

Muin J. Khoury ◽

J. David Erickson

Keyword(s):

Birth Defects ◽

Reproductive Behavior ◽

Birth Defect ◽

Large Population ◽

Population Based ◽

Subsequent Pregnancy ◽

Pregnancy Rates ◽

Wide Range ◽

First Year Of Life ◽

And Control

Objective. Data from a large population-based, case-control study were analyzed to determine whether women giving birth to children with major birth defects have different subsequent pregnancy patterns than those giving birth to live-born babies without defects. Other studies examining this phenomenon have been smaller, have not been population-based, or have not addressed the different effects that a wide range of major defects might have on mothers' subsequent pregnancy rates. Methods. Mothers of 4918 infants with major birth defects born from 1968 through 1980 in metropolitan Atlanta were compared with mothers of 3029 control infants, frequency-matched on birth year, birth hospital, and race. Results. The pregnancy rate in the first 3 years after the index birth was higher among case mothers (36%) than among control mothers (30%, P < .0001). This excess was seen for mothers of stillborn case infants (64%) and mothers of case infants who died in infancy (58%), but not for mothers of case infants who survived the first year of life (31%). Pregnancy rates varied by birth defect type. Maternal and infant factors varied among case and control subjects and influenced subsequent pregnancy rates. Conclusion. The reproductive behavior observed in this study supports the theory that mothers of nonsurviving children with birth defects compensate by acting to "replace" the lost child. Reproductive behavior was also strongly associated with having completed a previous pregnancy and by the type of birth defect.

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Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry

European Respiratory Journal ◽

10.1183/13993003.01592-2016 ◽

2017 ◽

Vol 49 (2) ◽

pp. 1601592 ◽

Cited By ~ 70

Author(s):

Helen E. Jo ◽

Ian Glaspole ◽

Christopher Grainge ◽

Nicole Goh ◽

Peter M.A. Hopkins ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Severity ◽

Large Population ◽

Underlying Disease ◽

National Registry ◽

Hazard Ratio ◽

Wide Range ◽

Baseline Characteristics

The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25–63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months–4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33–6.47, p<0.001) were strong predictors of mortality. Patients receiving anti-fibrotic medications had better survival (hazard ratio 0.56, 95% CI 0.34–0.92, p=0.022) than those not on anti-fibrotic medications, independent of underlying disease severity.The AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.

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2000 Fleming Lecture. The origin and evolution of hepatitis viruses in humans

Journal of General Virology ◽

10.1099/0022-1317-82-4-693 ◽

2001 ◽

Vol 82 (4) ◽

pp. 693-712 ◽

Cited By ~ 150

Author(s):

Peter Simmonds

Keyword(s):

Large Population ◽

Human Populations ◽

Hepatitis Viruses ◽

Hepatitis G Virus ◽

Origin And Evolution ◽

Wide Range ◽

Population Sizes ◽

History Of ◽

Virus C ◽

Time Of Divergence

The spread and origins of hepatitis C virus (HCV) in human populations have been the subject of extensive investigations, not least because of the importance this information would provide in predicting clinical outcomes and controlling spread of HCV in the future. However, in the absence of historical and archaeological records of infection, the evolution of HCV and other human hepatitis viruses can only be inferred indirectly from their epidemiology and by genetic analysis of contemporary virus populations. Some information on the history of the latter may be obtained by dating the time of divergence of various genotypes of HCV, hepatitis B virus (HBV) and the non-pathogenic hepatitis G virus (HGV)/GB virus-C (GBV-C). However, the relatively recent times predicted for the origin of these viruses fit poorly with their epidemiological distributions and the recent evidence for species-associated variants of HBV and HGV/GBV-C in a wide range of non-human primates. The apparent conservatism of viruses over long periods implied by these latter observations may be the result of constraints on sequence change peculiar to viruses with single-stranded genomes, or with overlapping reading frames. Large population sizes and intense selection pressures that optimize fitness may be the factors that set virus evolution apart from that of their hosts.

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Definitions of medication-overuse headache in population-based studies and their implications on prevalence estimates: A systematic review

Cephalalgia ◽

10.1177/0333102413512033 ◽

2013 ◽

Vol 34 (6) ◽

pp. 409-425 ◽

Cited By ~ 64

Author(s):

Maria L Westergaard ◽

Ebba Holme Hansen ◽

Charlotte Glümer ◽

Jes Olesen ◽

Rigmor H Jensen

Keyword(s):

Medication Overuse ◽

Medication Overuse Headache ◽

Large Population ◽

Population Based ◽

Case Definition ◽

Practical Case ◽

Case Definitions ◽

Wide Range ◽

Concurrent Medication ◽

Over Time

Background Case definitions of medication-overuse headache (MOH) in population-based research have changed over time. This study aims to review MOH prevalence reports with respect to these changes, and to propose a practical case definition for future studies based on the ICHD-3 beta. Methods A systematic literature search was conducted to identify MOH prevalence studies. Findings were summarized according to diagnostic criteria. Results Twenty-seven studies were included. The commonly used case definition for MOH was headache ≥15 days/month with concurrent medication overuse ≥3 months. There were varying definitions for what was considered as overuse. Studies that all used ICHD-2 criteria showed a wide range of prevalence among adults: 0.5%–7.2%. Conclusions There are limits to comparing prevalence of MOH across studies and over time. The wide range of reported prevalence might not only be due to changing criteria, but also the diversity of countries now publishing data. The criterion “headache occurring on ≥15 days per month” with concurrent medication overuse can be applied in population-based studies. However, the new requirement that a respondent must have “a preexisting headache disorder” has not been previously validated. Exclusion of other headache diagnoses by expert evaluation and ancillary examinations is not feasible in large population-based studies.

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Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter

Genetics Research ◽

10.1017/s0016672399004048 ◽

2000 ◽

Vol 75 (1) ◽

pp. 75-81 ◽

Cited By ~ 120

Author(s):

THOMAS BATAILLON ◽

MARK KIRKPATRICK

Keyword(s):

Population Size ◽

Inbreeding Depression ◽

Deleterious Mutation ◽

Large Population ◽

Genetic Load ◽

Breeding Systems ◽

Deleterious Mutations ◽

Single Locus Analysis ◽

Population Sizes ◽

Inbreeding Rate

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

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A Special Report on 2019 International Planning Competition and a Comprehensive Analysis of Its Results

Frontiers in Oncology ◽

10.3389/fonc.2020.571644 ◽

2020 ◽

Vol 10 ◽

Author(s):

Jiayun Chen ◽

Jianrong Dai ◽

Ahmad Nobah ◽

Sen Bai ◽

Nan Bi ◽

...

Keyword(s):

Work Experience ◽

Medical Physics ◽

Large Population ◽

Locally Advanced ◽

Planning System ◽

Treatment Planning System ◽

Plan Quality ◽

Wide Range ◽

The Mean ◽

International Planning

PurposeThe aim of this work is to introduce the 2019 International Planning Competition and to analyze its results.Methods and materialsA locally advanced non-small cell lung cancer (LA-NSCLC) case using the simultaneous integrated boost approach was selected. The plan quality was evaluated by using a ranking system in accordance with practice guidelines. Planners used their clinical Treatment Planning System (TPS) to generate the best possible plan along with a survey, designed to obtain medical physics aspects information. We investigated the quality of the large population of plans designed by worldwide planners using different planning and delivery systems. The correlations of plan quality with relevant planner characteristics (work experience, department scale, and competition experience) and with technological parameters (TPS and modality) were examined.ResultsThe number of the qualified plans was 287 with a wide range of scores (38.61–97.99). The scores showed statistically significant differences by the following factors: 1) department scale: the mean score (89.76 ± 8.36) for planners from the departments treating >2,000 patients annually was the highest of all; 2) competition experience: the mean score for the 107 planners with previous competition experience was 88.92 ± 9.59, statistically significantly from first-time participants (p = .001); 3) techniques: the mean scores for planners using VMAT (89.18 ± 6.43) and TOMO (90.62 ± 7.60) were higher than those using IMRT (82.28 ± 12.47), with statistical differences (p <.001). The plan scores were negligibly correlated with the planner’s years of work experience or the type of TPS used. Regression analysis demonstrated that plan score was associated with dosimetric objectives that were difficult to achieve, which is generally consistent with a clinical practice evaluation. However, 51.2% of the planners abandoned the difficult component of total lung receiving a dose of 5 Gy in their plan design to achieve the optimal plan.ConclusionThe 2019 international planning competition was carried out successfully, and its results were analyzed. Plan quality was not correlated with work experiences or the TPS used, but it was correlated with department scale, modality, and competition experience. These findings differed from those reported in previous studies.

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Experimental Investigations of Cycle-to-Cycle and Cylinder-to-Cylinder Variation of PCCI Combustion With High Injection Pressures

ASME 2010 Internal Combustion Engine Division Fall Technical Conference ◽

10.1115/icef2010-35021 ◽

2010 ◽

Cited By ~ 1

Author(s):

S. Juttu ◽

S. S. Thipse ◽

Praveen Mishra ◽

N. B. Dhande ◽

N. V. Marathe ◽

...

Keyword(s):

Diesel Engine ◽

Heat Release ◽

Injection Pressure ◽

Combustion Mode ◽

Operating Range ◽

High Injection ◽

Wide Range ◽

Significant Difference ◽

Low Load ◽

Injection Pressures

Recently HCCI combustion concept has gained the attention of industry and academia due to its potential to reduce NOx and PM emissions simultaneously from diesel engines. The HCCI concept also called as Partially-Premixed Charge Compression Ignition (PCCI) when heavy fuel like diesel is used as fuel. To achieve homogeneous mixture of diesel+air+residual gases, high injection pressures are required with fine atomization. The cycle-to-cycle and cylinder-to-cylinder variations in rail pressure and EGR ratio caused to variations in engine performance. In this study combustion stabilities and cycle-to-cycle variations of diesel engine operated in PCCI combustion mode were investigated at different fuel injection pressures on a 4-cylinder, 4-stroke diesel engine. The experiments were conducted with 500bar, 1000bar, 1500bar and 1800bar injection pressures at low load (IMEP = 2bar) and 50% load (IMEP = 8.5bar) at 2500 and 3000 rpm. No EGR was used at low load condition and 50% EGR was used at 50% load at all injection pressures. In-cylinder pressures of 100 cycles were recorded for each test conditions running with PCCI mode. Consequently, cycle-to-cycle variations of the maximum Rate of Heat Release (ROHRmax), maximum Total Heat Release (THRmax), IMEP and Pmax were analyzed and evaluated using Coefficient of Variation (COV) of each parameter. The significant difference in COV from cylinder-to-cylinder was observed at higher injection pressures. With high injection pressures, wide range of cycle-to-cycle variations were observed in engines operated in PCCI combustion mode limiting the injection pressure and operating range of engine. The results show that the injection pressure need to be optimized with respect to load to control the PCCI combustion at constant EGR ratio to minimize the cycle-to-cycle variations and also extend the operating range of PCCI mode.

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