Abstract
Background
Genome size is implicated in the form, function, and ecological success of a species. Two principally different mechanisms are proposed as major drivers of eukaryotic genome ...evolution and diversity: polyploidy (i.e., whole-genome duplication) or smaller duplication events and bursts in the activity of repetitive elements. Here, we generated de novo genome assemblies of 17 caddisflies covering all major lineages of Trichoptera. Using these and previously sequenced genomes, we use caddisflies as a model for understanding genome size evolution in diverse insect lineages.
Results
We detect a ∼14-fold variation in genome size across the order Trichoptera. We find strong evidence that repetitive element expansions, particularly those of transposable elements (TEs), are important drivers of large caddisfly genome sizes. Using an innovative method to examine TEs associated with universal single-copy orthologs (i.e., BUSCO genes), we find that TE expansions have a major impact on protein-coding gene regions, with TE-gene associations showing a linear relationship with increasing genome size. Intriguingly, we find that expanded genomes preferentially evolved in caddisfly clades with a higher ecological diversity (i.e., various feeding modes, diversification in variable, less stable environments).
Conclusion
Our findings provide a platform to test hypotheses about the potential evolutionary roles of TE activity and TE-gene associations, particularly in groups with high species, ecological, and functional diversities.
Objective
To examine functional status versus medical comorbidities as predictors of acute care readmissions in medically complex patients.
Design
Retrospective database study.
Setting
U.S. inpatient ...rehabilitation facilities.
Participants
Subjects included 120,957 patients in the Uniform Data System for Medical Rehabilitation admitted to inpatient rehabilitation facilities under the medically complex impairment group code between 2002 and 2011.
Interventions
A Basic Model based on gender and functional status was developed using logistic regression to predict the odds of 3-, 7-, and 30-day readmission from inpatient rehabilitation facilities to acute care hospitals. Functional status was measured by the FIM
®
motor score. The Basic Model was compared to six other predictive models—three Basic Plus Models that added a comorbidity measure to the Basic Model and three Gender-Comorbidity Models that included only gender and a comorbidity measure. The three comorbidity measures used were the Elixhauser index, Deyo-Charlson index, and Medicare comorbidity tier system. The c-statistic was the primary measure of model performance.
Main Outcome Measures
We investigated 3-, 7-, and 30-day readmission to acute care hospitals from inpatient rehabilitation facilities.
Results
Basic Model c-statistics predicting 3-, 7-, and 30-day readmissions were 0.69, 0.64, and 0.65, respectively. The best-performing Basic Plus Model (Basic+Elixhauser) c-statistics were only 0.02 better than the Basic Model, and the best-performing Gender-Comorbidity Model (Gender+Elixhauser) c-statistics were more than 0.07 worse than the Basic Model.
Conclusions
Readmission models based on functional status consistently outperform models based on medical comorbidities. There is opportunity to improve current national readmission risk models to more accurately predict readmissions by incorporating functional data.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Advanced functionality in molecular electronics and spintronics is orchestrated by exact molecular arrangements at metal surfaces, but the strategies for constructing such arrangements remain ...limited. Here, we report the synthesis and surface hybridization of a cyclophane that comprises two pyrene groups fastened together by two ferrocene pillars. Crystallographic structure analysis revealed pyrene planes separated by ∼352 pm and stacked in an eclipsed geometry that approximates the rare configuration of AA-stacked bilayer graphene. We deposited this cyclophane onto surfaces of Cu(111) and Co(111) at submonolayer coverage and studied the resulting hybrid entities with scanning tunnelling microscopy (STM). We found distinct characteristics of this cyclophane on each metal surface: on non-magnetic Cu(111), physisorption occurred and the two pyrene groups remained electronically coupled to each other; on ferromagnetic Co(111) nanoislands, chemisorption occurred and the two pyrene groups became electronically decoupled. Spin-polarized STM measurements revealed that the ferrocene groups had spin polarization opposite to that of the surrounding Co metal, while the pyrene stack had no spin polarization. Comparisons to the non-stacked analogue comprising only one pyrene group bolster our interpretation of the cyclophane's STM features. The design strategy presented herein can be extended to realize versatile, three-dimensional platforms in single-molecule electronics and spintronics.
A chemical strategy for the bottom-up construction of 3D spin interfaces is presented. Scanning tunnelling microscopy reveals distinct electronic features of a cyclophane with precisely designed pi-stacking on ferromagnetic Co(111) nanoislands.
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IJS, KILJ, NUK, UL, UM, UPUK
Data for trends in blood pressure are needed to understand the effects of its dietary, lifestyle, and pharmacological determinants; set intervention priorities; and evaluate national programmes. ...However, few worldwide analyses of trends in blood pressure have been done. We estimated worldwide trends in population mean systolic blood pressure (SBP). We estimated trends and their uncertainties in mean SBP for adults 25 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (786 country-years and 5.4 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean SBP by age, country, and year, accounting for whether a study was nationally representative. In 2008, age-standardised mean SBP worldwide was 128.1 mm Hg (95% uncertainty interval 126.7-129.4) in men and 124.4 mm Hg (123.0-125.9) in women. Globally, between 1980 and 2008, SBP decreased by 0.8 mm Hg per decade (-0.4 to 2.2, posterior probability of being a true decline=0.90) in men and 1.0 mm Hg per decade (-0.3 to 2.3, posterior probability=0.93) in women. Female SBP decreased by 3.5 mm Hg or more per decade in western Europe and Australasia (posterior probabilities ≥0.999). Male SBP fell most in high-income North America, by 2.8 mm Hg per decade (1.3-4.5, posterior probability >0.999), followed by Australasia and western Europe where it decreased by more than 2.0 mm Hg per decade (posterior probabilities >0.98). SBP rose in Oceania, east Africa, and south and southeast Asia for both sexes, and in west Africa for women, with the increases ranging 0.8-1.6 mm Hg per decade in men (posterior probabilities 0.72-0.91) and 1.0-2.7 mm Hg per decade for women (posterior probabilities 0.75-0.98). Female SBP was highest in some east and west African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and east and west African countries, where mean SBP reached 138 mm Hg or more. Men and women in western Europe had the highest SBP in high-income regions. On average, global population SBP decreased slightly since 1980, but trends varied significantly across regions and countries. SBP is currently highest in low-income and middle-income countries. Effective population-based and personal interventions should be targeted towards low-income and middle-income countries. Bill & Melinda Gates Foundation and WHO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the ...cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts of cognitive ageing, in vivo amyloid PET across two cohorts, and autopsy measures of amyloid neuritic plaque burden across two cohorts. These data were leveraged to build robust, continuous resilience phenotypes. With these phenotypes, we performed sex-stratified n (males) = 2093, n (females) = 2931 and sex-interaction n (both sexes) = 5024 genome-wide association studies (GWAS), gene and pathway-based tests, and genetic correlation analyses to clarify the variants, genes and molecular pathways that relate to resilience in a sex-specific manner. Estimated among cognitively normal individuals of both sexes, resilience was 20-25% heritable, and when estimated in either sex among cognitively normal individuals, resilience was 15-44% heritable. In our GWAS, we identified a female-specific locus on chromosome 10 rs827389, β (females) = 0.08, P (females) = 5.76 × 10-09, β (males) = -0.01, P(males) = 0.70, β (interaction) = 0.09, P (interaction) = 1.01 × 10-04 in which the minor allele was associated with higher resilience scores among females. This locus is located within chromatin loops that interact with promoters of genes involved in RNA processing, including GATA3. Finally, our genetic correlation analyses revealed shared genetic architecture between resilience phenotypes and other complex traits, including a female-specific association with frontotemporal dementia and male-specific associations with heart rate variability traits. We also observed opposing associations between sexes for multiple sclerosis, such that more resilient females had a lower genetic susceptibility to multiple sclerosis, and more resilient males had a higher genetic susceptibility to multiple sclerosis. Overall, we identified sex differences in the genetic architecture of resilience, identified a female-specific resilience locus and highlighted numerous sex-specific molecular pathways that may underly resilience to Alzheimer's disease pathology. This study illustrates the need to conduct sex-aware genomic analyses to identify novel targets that are unidentified in sex-agnostic models. Our findings support the theory that the most successful treatment for an individual with Alzheimer's disease may be personalized based on their biological sex and genetic context.
Kidney disease is associated with an increased risk for postoperative morbidity and mortality. However, the incidence of major surgery on a population level is unknown. We aimed to determine the ...incidence of major surgery by level of kidney function.
Retrospective cohort study with entry from January 1, 2008, through December 31, 2009, and outcome surveillance from January 1, 2010, through December 31, 2016.
Population-based study using administrative health data from Alberta, Canada; adults with an outpatient serum creatinine measurement or receiving maintenance dialysis formed the study cohort.
Participants were categorized into 6 estimated glomerular filtration rate (eGFR) categories: ≥60 (G1-G2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), and<15mL/min/1.73m2 with (G5D) and without (G5) dialysis. eGFR was examined as a time-varying exposure based on means of measurements within 3-month ascertainment periods throughout the study period.
Major surgery defined as surgery requiring admission to the hospital for at least 24 hours.
Incidence rates (IRs) for overall major surgery were estimated using quasi-Poisson regression and adjusted for age, sex, income, location of residence, albuminuria, and Charlson comorbid conditions. Age- and sex-stratified IRs of 13 surgery subtypes were also estimated.
1,455,512 cohort participants were followed up for a median of 7.0 (IQR, 5.3) years, during which time 241,989 (16.6%) underwent a major surgery. Age and sex modified the relationship between eGFR and incidence of surgery. Men younger than 65 years receiving maintenance dialysis experienced the highest rates of major surgery, with an adjusted IR of 243.8 (95% CI, 179.8-330.6) per 1,000 person-years. There was a consistent trend of increasing surgery rates at lower eGFRs for most subtypes of surgery.
Outpatient preoperative serum creatinine measurement was necessary for inclusion and outpatient surgical procedures were not included.
People with reduced eGFR have a significantly higher incidence of major surgery compared with those with normal eGFR, and age and sex modify this increased risk. This study informs our understanding of how surgical burden changes with differing levels of kidney function.
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A
bstract
We report a new measurement of the
e
+
e
−
→
ϒ(
nS
)
π
+
π
−
(
n
= 1
,
2
,
3) cross sections at energies from 10
.
52 to 11
.
02 GeV using data collected with the Belle detector at the KEKB ...asymmetric-energy
e
+
e
−
collider. We observe a new structure in the energy dependence of the cross sections; if described by a Breit-Wigner function its mass and width are found to be
M
=
10752.7
±
5.9
−
1.1
+
0.7
MeV
/
c
2
and
Γ
=
35.5
−
11.3
−
3.3
+
17.6
+
3.9
MeV, where the first error is statistical and the second is systematic. The global significance of the new structure including systematic uncertainty is 5.2 standard deviations. We also find evidence for the
e
+
e
−
→
ϒ (1
S
)
π
+
π
−
process at the energy 10
.
52 GeV, which is below the
B
B
¯
threshold.
The transforming-growth-factor-beta-activated kinase TAK1 is a member of the mitogen-activated protein kinase kinase kinase family, which couples extracellular stimuli to gene transcription. The in ...vivo function of TAK1 is not understood. Here, we investigated the potential involvement of TAK1 in cardiac hypertrophy. In adult mouse myocardium, TAK1 kinase activity was upregulated 7 days after aortic banding, a mechanical load that induces hypertrophy and expression of transforming growth factor beta. An activating mutation of TAK1 expressed in myocardium of transgenic mice was sufficient to produce p38 mitogen-activated protein kinase phosphorylation in vivo, cardiac hypertrophy, interstitial fibrosis, severe myocardial dysfunction, 'fetal' gene induction, apoptosis and early lethality. Thus, TAK1 activity is induced as a delayed response to mechanical stress, and can suffice to elicit myocardial hypertrophy and fulminant heart failure.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were ...submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS.
From April 2014-October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84).
Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.
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