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Ultralow-threshold, continuous-wave upconverting lasing from subwavelength plasmons.
Miniaturized lasers are an emerging platform for generating coherent light for quantum photonics, in vivo cellular imaging, solid-state lighting and fast three-dimensional sensing in smartphones1-3. Continuous-wave lasing at room temperature is critical for integration with opto-electronic devices and optimal modulation of optical interactions4,5. Plasmonic nanocavities integrated with gain can generate coherent light at subwavelength scales6-9, beyond the diffraction limit that constrains mode volumes in dielectric cavities such as semiconducting nanowires10,11. However, insufficient gain with respect to losses and thermal instabilities in nanocavities has limited all nanoscale lasers to pulsed pump sources and/or low-temperature operation6-9,12-15. Here, we show continuous-wave upconverting lasing at room temperature with record-low thresholds and high photostability from subwavelength plasmons. We achieve selective, single-mode lasing from Yb3+/Er3+-co-doped upconverting nanoparticles conformally coated on Ag nanopillar arrays that support a single, sharp lattice plasmon cavity mode and greater than wavelength λ/20 field confinement in the vertical dimension. The intense electromagnetic near-fields localized in the vicinity of the nanopillars result in a threshold of 70âWâcm-2, orders of magnitude lower than other small lasers. Our plasmon-nanoarray upconverting lasers provide directional, ultra-stable output at visible frequencies under near-infrared pumping, even after six hours of constant operation, which offers prospects in previously unrealizable applications of coherent nanoscale light
A 27-year review of mergers and acquisitions research in 27 leading management journals
This study contributes to the existing body of knowledge on mergers and acquisitions (M&As) by providing a systematic review of over 500 academic articles across 27 management journals over a 27-year time frame. There appears to be a mixture of empirical and conceptual articles, with a larger proportion being empirical but an increasing number leaning towards a conceptual nature. Our findings show that most studies follow a quantitative approach and use large samples, mostly originating from existing databases. There is an emergence of thematic areas related to the strategic factors influencing M&As, but with the human dimension, gaining increasing attention over time.authorsversionpublishe
Indefinite and Bidirectional Near Infrared Nanocrystal Photoswitching
Materials whose luminescence can be switched by optical stimulation drive
technologies ranging from superresolution imaging1-4, nanophotonics5, and
optical data storage6-8, to targeted pharmacology, optogenetics, and chemical
reactivity9. These photoswitchable probes, including organic fluorophores and
proteins, are prone to photodegradation, and often require phototoxic doses of
ultraviolet (UV) or visible light. Colloidal inorganic nanoparticles have
significant stability advantages over existing photoswitchable materials, but
the ability to switch emission bidirectionally, particularly with NIR light,
has not been reported with nanoparticles. Here, we present 2-way, near-infrared
(NIR) photoswitching of avalanching nanoparticles (ANPs), showing full optical
control of upconverted emission using phototriggers in the NIR-I and NIR-II
spectral regions useful for subsurface imaging. Employing single-step
photodarkening10-13 and photobrightening12,14-18, we demonstrate indefinite
photoswitching of individual nanoparticles (>1000 cycles over 7 h) in ambient
or aqueous conditions without measurable photodegradation. Critical steps of
the photoswitching mechanism are elucidated by modeling and by measuring the
photon avalanche properties of single ANPs in both bright and dark states.
Unlimited, reversible photoswitching of ANPs enables indefinitely rewritable 2D
and 3D multi-level optical patterning of ANPs, as well as optical nanoscopy
with sub-{\AA} localization superresolution that allows us to distinguish
individual ANPs within tightly packed clusters.Comment: 15 pages, 5 figure
'To live and die [for] Dixie': Irish civilians and the Confederate States of America
Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism
Prognostic factors affecting survival after surgical resection of gastrointestinal stromal tumours: a two-unit experience over 10 years
BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been recently described based on their specific immunohistochemistry and the presence of particular KIT-related mutations which potentially make them targets for tyrosine kinase inhibition. METHODS: Sixty-one patients (29 M; 32 F, median age 60 years; range: 23â86 years) between June 1994 and March 2005, were analyzed from two allied institutions. Patient, tumour, and treatment variables were analyzed to identify factors affecting survival. RESULTS: Of the 61 patients, 55 (90%) underwent complete surgical resection of macroscopic disease. The 5-year overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis revealed that R0 resection was strongly associated with a better OSrate (p < 0.0001). Likewise, univariate analysis also showed high mitotic count of > 10 mitoses/per 50 HPF was a significant variable in worse prognosis for OS (†10 mitoses/per 50 HPF 95% 5-year OS vs. > 10 mitoses/per 50 HPF 74% 5-year OS, respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic count remained as a significant negative prognostic variable for OS (p = 0.029). Among patients resected for cure, there were 8 recurrences during follow-up. The mean time to recurrence was 21 ± 10 months (range: 4â36 months). Univariate analysis revealed that mitotic count of > 10 mitoses per 50 high power fields, intratumoural necrosis, and pathological tumour size (> 10 cm in maximal diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02, respectively), with tumour necrosis and high mitotic count remaining as independent predictive variables affecting prognosis on subsequent multivariate analysis. CONCLUSION: Most GISTs are resectable with survival principally dependent upon mitotic count and completeness of resection. Future metabolic and genetic analyses will define the role of and resistance to induction or postoperative adjuvant targeted kinase inhibition therapy
Status and prospects for renewable energy using wood pellets from the southeastern United States
The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, âHow is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?â To address this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management
ĐĐœŃĐžĐșŃОзОŃĐœĐŸĐ” ŃĐżŃĐ°ĐČĐ»Đ”ĐœĐžĐ”
ĐŁŃĐ”Đ±ĐœĐŸ-ĐŒĐ”ŃĐŸĐŽĐžŃĐ”ŃĐșĐžĐč ĐșĐŸĐŒĐżĐ»Đ”ĐșŃ (ĐŁĐĐ) ĐżĐŸ ŃŃĐ”Đ±ĐœĐŸĐč ĐŽĐžŃŃĐžĐżĐ»ĐžĐœĐ” «ĐĐœ-ŃĐžĐșŃОзОŃĐœĐŸĐ” ŃĐżŃĐ°ĐČĐ»Đ”ĐœĐžĐ”Â» ŃĐŸĐ·ĐŽĐ°Đœ ĐČ ŃĐŸĐŸŃĐČĐ”ŃŃŃĐČОО Ń ŃŃĐ”Đ±ĐŸĐČĐ°ĐœĐžŃĐŒĐž ĐĐŸĐ»ĐŸĐ¶Đ”ĐœĐžŃ ĐŸĐ± ŃŃĐ”Đ±ĐœĐŸ-ĐŒĐ”ŃĐŸĐŽĐžŃĐ”ŃĐșĐŸĐŒ ĐșĐŸĐŒĐżĐ»Đ”ĐșŃĐ” ĐœĐ° ŃŃĐŸĐČĐœĐ” ĐČŃŃŃĐ”ĐłĐŸ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ĐœĐžŃ, ŃŃĐČĐ”Ń-Đ¶ĐŽĐ”ĐœĐœĐŸĐłĐŸ ĐżĐŸŃŃĐ°ĐœĐŸĐČĐ»Đ”ĐœĐžĐ”ĐŒ ĐĐžĐœĐžŃŃĐ”ŃŃŃĐČĐ° ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ĐœĐžŃ Đ Đ”ŃĐżŃблОĐșĐž ĐДлаŃŃŃŃ ĐŸŃ 26.07.2011 â 167, ĐżŃĐ”ĐŽĐœĐ°Đ·ĐœĐ°ŃĐ”Đœ ĐŽĐ»Ń ŃДалОзаŃОО ŃĐŸĐŽĐ”ŃĐ¶Đ°ĐœĐžŃ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°-ŃДлŃĐœĐŸĐč ĐżŃĐŸĐłŃĐ°ĐŒĐŒŃ ĐŽĐ»Ń ĐŸĐ±ŃŃĐ°ŃŃĐžŃ
ŃŃ ĐżĐ”ŃĐČĐŸĐč ŃŃŃĐżĐ”ĐœĐž ĐČŃŃŃĐ”ĐłĐŸ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ĐœĐžŃ ĐŽĐ»Ń ŃŃŃĐŽĐ”ĐœŃĐŸĐČ ŃпДŃОалŃĐœĐŸŃŃĐž 1-26 02-02 «ĐĐ”ĐœĐ”ĐŽĐ¶ĐŒĐ”ĐœŃ».
ĐĄĐŸĐŽĐ”ŃĐ¶Đ°ĐœĐžĐ” ŃĐ°Đ·ĐŽĐ”Đ»ĐŸĐČ ĐŁĐĐ ŃĐŸĐŸŃĐČĐ”ŃŃŃĐČŃĐ”Ń ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ŃДлŃĐœĐŸĐŒŃ ŃŃĐ°ĐœĐŽĐ°ŃŃŃ ĐČŃŃŃĐ”ĐłĐŸ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ĐœĐžŃ ĐŽĐ°ĐœĐœĐŸĐč ŃпДŃОалŃĐœĐŸŃŃĐž.
ĐлаĐČĐœĐ°Ń ŃĐ”Đ»Ń ĐŁĐĐ â ĐŸĐșĐ°Đ·Đ°ĐœĐžĐ” ĐŒĐ”ŃĐŸĐŽĐžŃĐ”ŃĐșĐŸĐč ĐżĐŸĐŒĐŸŃĐž ĐŒĐ°ĐłĐžŃŃŃĐ°ĐœŃĐ°ĐŒ ĐČ ĐŸŃĐČĐŸĐ”ĐœĐžĐž Đž ŃĐžŃŃĐ”ĐŒĐ°ŃОзаŃОО ŃŃĐ”Đ±ĐœĐŸĐłĐŸ ĐŒĐ°ŃĐ”ŃОала ĐČ ĐżŃĐŸŃĐ”ŃŃĐ” ĐŸĐ±ŃŃĐ”ĐœĐžŃ Đž ĐżĐŸĐŽ-ĐłĐŸŃĐŸĐČĐșĐž Đș Đ°ŃŃĐ”ŃŃĐ°ŃОО ĐżĐŸ ĐŽĐžŃŃĐžĐżĐ»ĐžĐœĐ” «ĐĐœŃĐžĐșŃОзОŃĐœĐŸĐ” ŃĐżŃĐ°ĐČĐ»Đ”ĐœĐžĐ”Â».
ĐŁĐĐ ĐČĐșĐ»ŃŃĐ°Đ”Ń:
1. ĐąĐ”ĐŸŃĐ”ŃĐžŃĐ”ŃĐșĐžĐč ŃазЎДл (ĐșĐŸĐœŃпДĐșŃ Đ»Đ”ĐșŃĐžĐč, Đ°ĐœĐœĐŸŃĐžŃĐŸĐČĐ°ĐœĐœŃĐč пДŃĐ”ŃĐ”ĐœŃ ĐŸŃĐœĐŸĐČĐœŃŃ
ŃŃĐ”Đ±ĐœŃŃ
Đž ĐœĐ°ŃŃĐœĐŸ-ĐżŃĐ°ĐșŃĐžŃĐ”ŃĐșĐžŃ
ĐžĐ·ĐŽĐ°ĐœĐžĐč).
2. ĐŃĐ°ĐșŃĐžŃĐ”ŃĐșĐžĐč ŃазЎДл (ŃĐ”ĐŒĐ°ŃĐžĐșĐ° ĐżŃĐ°ĐșŃĐžŃĐ”ŃĐșĐžŃ
Đ·Đ°ĐœŃŃĐžĐč ĐżĐŸ ĐŽĐžŃŃĐž-ĐżĐ»ĐžĐœĐ” ĐČ ŃĐŸĐŸŃĐČĐ”ŃŃŃĐČОО Ń ŃŃĐ”Đ±ĐœŃĐŒ ĐżĐ»Đ°ĐœĐŸĐŒ Đž ŃŃĐ”Đ±ĐœĐŸĐč ĐżŃĐŸĐłŃĐ°ĐŒĐŒĐŸĐč).
3. ĐĐŸĐœŃŃĐŸĐ»Ń ŃĐ°Đ±ĐŸŃŃ ĐŸĐ±ŃŃĐ°ŃŃĐžŃ
ŃŃ (ĐŒĐ°ŃĐ”ŃĐžĐ°Đ»Ń ĐŽĐ»Ń ŃĐ”ĐșŃŃĐ”Đč Đ°ŃŃĐ”ŃŃĐ°ŃОО, ĐżĐŸĐ·ĐČĐŸĐ»ŃŃŃОД ĐŸĐżŃДЎДлОŃŃ ŃĐŸĐŸŃĐČĐ”ŃŃŃĐČОД ŃŃĐ”Đ±ĐœĐŸĐč ĐŽĐ”ŃŃДлŃĐœĐŸŃŃĐž ĐŸĐ±ŃŃĐ°ŃŃĐžŃ
ŃŃ ŃŃĐ”Đ±ĐŸĐČĐ°ĐœĐžŃĐŒ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ŃДлŃĐœĐŸĐłĐŸ ŃŃĐ°ĐœĐŽĐ°ŃŃĐ° ĐČŃŃŃĐ”ĐłĐŸ ĐŸĐ±ŃĐ°Đ·ĐŸĐČĐ°ĐœĐžŃ Đž ŃŃĐ”Đ±ĐœĐŸ-ĐżŃĐŸĐłŃĐ°ĐŒĐŒĐœĐŸĐč ĐŽĐŸĐșŃĐŒĐ”ĐœŃĐ°ŃОО, ĐČ Ń.Ń. ĐČĐŸĐżŃĐŸŃŃ ĐŽĐ»Ń ĐżĐŸĐŽĐłĐŸŃĐŸĐČĐșĐž Đș Đ·Đ°ŃĐ”ŃŃ).
4. ĐŃĐżĐŸĐŒĐŸĐłĐ°ŃДлŃĐœŃĐč ŃазЎДл (ŃĐŸĐŽĐ”ŃĐ¶Đ°ĐœĐžĐ” ŃŃĐ”Đ±ĐœĐŸĐłĐŸ ĐŒĐ°ŃĐ”ŃОала ŃŃĐ”Đ±ĐœĐŸĐč ĐŽĐžŃŃĐžĐżĐ»ĐžĐœŃ; ĐŒĐ”ŃĐŸĐŽĐžŃĐ”ŃĐșОД ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐ°ŃОО ĐżĐŸ ĐŸŃĐłĐ°ĐœĐžĐ·Đ°ŃОО ŃĐ°ĐŒĐŸŃŃĐŸŃŃДлŃĐœĐŸĐč ŃĐ°Đ±ĐŸŃŃ ĐŒĐ°ĐłĐžŃŃŃĐ°ĐœŃĐŸĐČ; ĐžĐœŃĐŸŃĐŒĐ°ŃĐžĐŸĐœĐœĐŸ-Đ°ĐœĐ°Đ»ĐžŃĐžŃĐ”ŃĐșОД ĐŒĐ°ŃĐ”ŃОалŃ: ŃпОŃĐŸĐș ŃĐ”-ĐșĐŸĐŒĐ”ĐœĐŽŃĐ”ĐŒĐŸĐč лОŃĐ”ŃĐ°ŃŃŃŃ, пДŃĐ”ŃĐ”ĐœŃ ŃлДĐșŃŃĐŸĐœĐœŃŃ
ŃĐ”ŃŃŃŃĐŸĐČ Đž ĐžŃ
Đ°ĐŽŃĐ”ŃĐ°; ĐżŃĐž-ĐŒĐ”ŃĐœŃĐč пДŃĐ”ŃĐ”ĐœŃ ŃĐ”ĐŒ ĐŽĐ»Ń ĐœĐ°ĐżĐžŃĐ°ĐœĐžŃ ŃĐ”ŃĐ”ŃĐ°ŃĐŸĐČ).
Đ Đ°Đ±ĐŸŃĐ° Ń ĐŁĐĐ ĐŽĐŸĐ»Đ¶ĐœĐ° ĐČĐșĐ»ŃŃĐ°ŃŃ ĐœĐ° пДŃĐČĐŸĐŒ ŃŃапД ĐŸĐ·ĐœĐ°ĐșĐŸĐŒĐ»Đ”ĐœĐžĐ” Ń ŃĐŸ-ĐŽĐ”ŃĐ¶Đ°ĐœĐžĐ”ĐŒ ŃŃĐ”Đ±ĐœĐŸĐłĐŸ ĐŒĐ°ŃĐ”ŃОала ŃŃĐ”Đ±ĐœĐŸĐč ĐŽĐžŃŃĐžĐżĐ»ĐžĐœŃ, ĐżĐŸŃŃДЎŃŃĐČĐŸĐŒ ĐșĐŸŃĐŸŃĐŸĐłĐŸ ĐŒĐŸĐ¶ĐœĐŸ ĐżĐŸĐ»ŃŃĐžŃŃ ĐžĐœŃĐŸŃĐŒĐ°ŃĐžŃ ĐŸ ŃĐ”ĐŒĐ°ŃĐžĐșĐ” лДĐșŃĐžĐč Đž ĐżŃĐ°ĐșŃĐžŃĐ”ŃĐșĐžŃ
Đ·Đ°ĐœŃŃĐžĐč, пДŃĐ”ŃĐœŃŃ
ŃĐ°ŃŃĐŒĐ°ŃŃĐžĐČĐ°Đ”ĐŒŃŃ
ĐČĐŸĐżŃĐŸŃĐŸĐČ Đž ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽŃĐ”ĐŒĐŸĐč ĐŽĐ»Ń ĐžŃ
ОзŃŃĐ”ĐœĐžŃ Đ»Đž-ŃĐ”ŃĐ°ŃŃŃŃ. ĐĐ»Ń ĐżĐŸĐŽĐłĐŸŃĐŸĐČĐșĐž Đș ĐżŃĐ°ĐșŃĐžŃĐ”ŃĐșĐžĐŒ Đ·Đ°ĐœŃŃĐžŃĐŒ ĐœĐ”ĐŸĐ±Ń
ĐŸĐŽĐžĐŒĐŸ ĐžŃĐżĐŸĐ»ŃĐ·ĐŸ-ĐČĐ°ŃŃ ĐŒĐ°ŃĐ”ŃОалŃ, ĐżŃДЎŃŃĐ°ĐČĐ»Đ”ĐœĐœŃĐ” ĐČ ĐąĐ”ĐŸŃĐ”ŃĐžŃĐ”ŃĐșĐŸĐŒ Đž ĐŃĐ°ĐșŃĐžŃĐ”ŃĐșĐŸĐŒ ŃазЎДлаŃ
.
Đ ĐŸŃĐœĐŸĐČŃ ŃŃŃŃĐșŃŃŃŃ ĐżŃĐŸĐłŃĐ°ĐŒĐŒŃ Đ»Đ”ĐłĐ»Đ° ŃŃĐ”Đ±ĐœĐ°Ń ĐżŃĐŸĐłŃĐ°ĐŒĐŒĐ° «ĐĐœŃĐžĐșŃĐž-Đ·ĐžŃĐœĐŸĐ” ŃĐżŃĐ°ĐČĐ»Đ”ĐœĐžĐ”Â» ĐĐ”Đ»ĐŸŃŃŃŃĐșĐŸĐłĐŸ ĐłĐŸŃŃĐŽĐ°ŃŃŃĐČĐ”ĐœĐœĐŸĐłĐŸ ŃĐœĐžĐČĐ”ŃŃĐžŃĐ”ŃĐ° ĐŽĐ»Ń ĐČŃŃ-ŃĐžŃ
ŃŃĐ”Đ±ĐœŃŃ
Đ·Đ°ĐČĐ”ĐŽĐ”ĐœĐžĐč ĐżĐŸ ŃпДŃОалŃĐœĐŸŃŃĐž Đ.01.03.00 «ĐĐșĐŸĐœĐŸĐŒĐžĐșĐ° Đž ŃĐżŃĐ°ĐČлД-ĐœĐžŃ ĐœĐ° ĐżŃДЎпŃĐžŃŃОО» (ŃДгОŃŃŃĐ°ŃĐžĐŸĐœĐœŃĐč â ĐąĐ-182/баз.)
Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe
DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies
Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe
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