Evidence map›Paper›PMID 26103466›Full record

ArticlePloS one2015

Age and Sex of Mice Markedly Affect Survival Times Associated with Hyperoxic Acute Lung Injury.

Daniel R Prows, William J Gibbons, Jessica J Smith, Valentina Pilipenko, Lisa J Martin

Abstract readComparative Study
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Observational
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Daniel R ProwsDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
William J GibbonsDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Jessica J SmithDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Valentina PilipenkoDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Lisa J MartinDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America; Division of Biostatistics & Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.

Funding

Genetic Analysis of Hyperoxia Induced Acute Lung InjuryR01HL075562 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PROWS, DANIEL R · 2004 to 2012
$3.0M
Genetic Analysis of Hyperoxia Induced Acute Lung InjuryR56HL075562 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI PROWS, DANIEL R · 2008 to 2008
$378k
NHLBI NIH HHS HL075562NHLBI NIH HHS R01 HL075562NHLBI NIH HHS R56 HL075562
6 · The paper itself

Abstract

Mortality associated with acute lung injury (ALI) remains substantial, with recent estimates of 35-45% similar to those obtained decades ago. Although evidence for sex-related differences in ALI mortality remains equivocal, death rates differ markedly for age, with more than 3-fold increased mortality in older versus younger patients. Strains of mice also show large differences in ALI mortality. To tease out genetic factors affecting mortality, we established a mouse model of differential hyperoxic ALI (HALI) survival. Separate genetic analyses of backcross and F2 populations generated from sensitive C57BL/6J (B) and resistant 129X1/SvJ (X1) progenitor strains identified two quantitative trait loci (QTLs; Shali1 and Shali2) with strong, equal but opposite, within-strain effects on survival. Congenic lines confirmed these opposing QTL effects, but also retained the low penetrance seen in the 6-12 week X1 control strain. Sorting mice into distinct age groups revealed that 'age at exposure' inversely correlated with survival time and explained reduced penetrance of the resistance trait. While B mice were already sensitive by 6 weeks old, X1 mice maintained significant resistance up to 3-4 weeks longer. Reanalysis of F2 data gave analogous age-related findings, and also supported sex-specific linkage for Shali1 and Shali2. Importantly, we have demonstrated in congenic mice that these age effects on survival correspond with B alleles for Shali1 (6-week old mice more sensitive) and Shali2 (10-week old mice more resistant) placed on the X1 background. Further studies revealed significant sex-specific survival differences in subcongenics for both QTLs. Accounting for age and sex markedly improved penetrance of both QTLs, thereby reducing trait variability, refining Shali1 to <8.5Mb, and supporting several sub-QTLs within the Shali2 interval. Together, these congenics will allow age- and sex-specific studies to interrogate myriad subphenotypes affected during ALI development and progression and identify intermediary injury biomarkers that can predict outcome.

Indexed as

Age FactorsSex FactorsAcute Lung InjuryAnimalsAnimals, CongenicFemaleGenotypeHyperoxiaInbreedingMaleMiceMice, 129 StrainMice, Inbred C57BLQuantitative Trait LociSurvival

Identifiers

PMID26103466
PMCPMC4478006

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.