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| 2. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Rong, Yu, et al.
(author)
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Multicolor Fluorescent Semiconducting Polymer Dots with Narrow Emissions and High Brightness
- 2013
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In: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 7:1, s. 376-384
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Journal article (peer-reviewed)abstract
- Fluorescent semiconducting polymer dots (Pdots) have attracted great interest because of their superior characteristics as fluorescent probes, such as high fluorescence brightness, fast radiative rates, and excellent photostability. However, currently available Pdots generally exhibit broad emission spectra, which significantly limit their usefulness in many biological applications Involving multiplex detections. Here, we describe the design and development of multicolor narrow emissive Pdots based on different boron dipyrromethene (BODIPY) units. BODIPY-containing semiconducting polymers emitting at multiple wavelengths were synthesized and used as precursors for preparing the Pdots, where intraparticle energy transfer led to highly bright, narrow emissions. The emission full width at half-maximum of the resulting Pdots varies from 40 to 55 nm, which is 15-2 times narrower than those of conventional semiconducting polymer dots. BODIPY 520 Pdots were about an order of magnitude brighter than commercial Qdot 525 under identical laser excitation conditions. Fluorescence imaging and flow cytometry experiments indicate that the narrow emissions from these bright Pdots are promising for multiplexed biological detections.
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| 4. |
- Samia, Pauline, et al.
(author)
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Telemedicine for Individuals with epilepsy: Recommendations from the International League Against Epilepsy Telemedicine Task Force.
- 2023
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In: Seizure. - : Elsevier BV. - 1532-2688 .- 1059-1311. ; 106, s. 85-91
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Research review (peer-reviewed)abstract
- Worldwide, People with Epilepsy (PWE) are confronted with several barriers to face-to-face consultations. These obstacles hamper appropriate clinical follow-up and also increase the treatment gap for Epilepsy. Telemedicine holds the potential to enhance management as follow-up visits for PWE are focused on more on clinical history and counselling rather than physical examination. Besides consultation, telemedicine can also be used for remote EEG diagnostics and tele-neuropsychology assessments. In this article, the Telemedicine Task Force of the International League Against Epilepsy (ILAE) outlines recommendations regarding optimal practice in utilizing in the management of individuals with epilepsy. We formulated recommendations for minimum technical requirements, preparing for the first tele-consultation and the specificities for follow-up consultations. Special considerations are necessary for specific populations, including paediatric patients, patients who are not conversant with tele-medicine and those with intellectual disability. Telemedicine for individuals with epilepsy should be vigorously promoted with the aim of improving the quality of care and ultimately reduce the wide clinician access related treatment gap across several regions of the globe.
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| 5. |
- Wang, Haidong, et al.
(author)
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Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
- 2016
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In: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
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Journal article (peer-reviewed)abstract
- BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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| 7. |
- Abramson, Alex, et al.
(author)
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A luminal unfolding microneedle injector for oral delivery of macromolecules
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:10, s. 1512-
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Journal article (peer-reviewed)abstract
- Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes(1,2), yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications(3-5). Compared with subcutaneously administered drugs, oral formulations create less patient discomfort(4), show greater chemical stability at high temperatures(6), and do not generate biohazardous needle waste(7). An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract(8). We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake > 10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.
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| 8. |
- Chen, Yu-Hsiang, et al.
(author)
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Effects of decomposition route and microstructure on h-AlN formation rate in TiCrAlN alloys
- 2017
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In: Journal of Alloys and Compounds. - : ELSEVIER SCIENCE SA. - 0925-8388 .- 1873-4669. ; 691, s. 1024-1032
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Journal article (peer-reviewed)abstract
- The phase evolution of cubic (c), solid solution TixCr-0.37Al1-0.37-x N alloys with x = 0.03 and 0.16, and the kinetics of the hexagonal (h)-AlN formation are studied via in situ wide angle x-ray scattering experiments during high temperature (1000-1150 degrees C) annealing. Spinodal decomposition was observed in Ti0.16Cr0.36Al0.48N while Ti0.03Cr0.38Al0.59N decomposes through nucleation and growth of h-AlN, c-TiN and c-CrAlN. h-AlN is formed from c-CrAlN domains in both cases and the formation rate of h-AlN depends on the stability of the c-CrAlN domains. In Ti0.16Cr0.36Al0.48N, the c-CrAlN domains are stabilized by crystallographic coherency with the surrounding c-TiCrN in a microstructure originating from spinodal decomposition. This results in lower formation rates of h-AlN for this composition. These differences are reflected in higher activation energy for h-AlN formation in Ti0.16Cr0.36Al0.48N compared to Ti0.03Cr0.38Al0.59N. It also points out different stabilities of the intermediate phase c-CrAlN during phase decomposition of TiCrAlN alloys. Additional contributions to the low activation energy for formation of h-AlN in Ti0.03Cr0.38Al0.59N stems from precipitation at grain boundaries. (C) 2016 Elsevier B.V. All rights reserved.
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| 9. |
- Chen, Yu-Hsiang, et al.
(author)
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Enhanced thermal stability and fracture toughness of TiAlN coatings by Cr, Nb and V-alloying
- 2018
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In: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 342, s. 85-93
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Journal article (peer-reviewed)abstract
- The effect of metal alloying on mechanical properties including hardness and fracture toughness were investigated in three alloys, Ti 0.33Al0.50(Me) 0.17N (Me = Cr, Nb and V), and compared to Ti0.50Al0.50N, in the as-deposited state and after annealing. All studied alloys display similar as-deposited hardness while the hardness evolution during annealing is found to be connected to phase transformations, related to the alloy’s thermal stability. The most pronounced hardening was observed in Ti0.50Al0.50N, while all the coatings with additional metal elements sustain their hardness better and they are harder than Ti0.50Al0.50N after annealing at 1100 °C. Fracture toughness properties were extracted from scratch tests. In all tested conditions, as-deposited and annealed at 900 and 1100 °C, Ti0.33Al0.50Nb0.17N show the least surface and sub-surface damage when scratched despite the differences in decomposition behavior and h-AlN formation. Theoretically estimated ductility of phases existing in the coatings correlates well with their crack resistance. In summary, Ti0.33Al0.50Nb0.17N is the toughest alloy in both as-deposited and post-annealed states.
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| 10. |
- Chen, Yu-Hsiang
(author)
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Mechanical and thermal stability of hard nitride coatings
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Hard coating’s thermal stability is essential due to the high temperature environment of high-speed cutting applications, while the phase and microstructure evolution induced by exposing the coating to high temperature affects the mechanical properties. In this thesis, the mechanical stability of arc-evaporated, hard, transition metal nitride coatings annealed at high temperature is analyzed and related to the phase and microstructure evolution. In addition to hardness, fracture toughness is evaluated by surface and cross-sectional investigations by scanning/transmission electron microscopy of damage events following mechanical tests.The crack resistance of Ti1−xAlxN with a range of Al content (x = 0.23-0.82) was studied by contact fatigue tests, where the differences in the microstructure were found to play a major role. Superior mechanical properties were found in Ti0.63Al0.37N; in the as-deposited state as a result of a favorable grain size, and after annealing at 900o C due to the microstructure formed during spinodal decomposition.The mechanical and high-temperature properties of hard coatings can be enhanced by alloying or multi-layering. Within this work, quaternary Ti-Al-X-N (X = Cr, Nb and V) alloys were studied and superior toughness was found for TiAl(Nb)N in both the as-deposited and annealed (1100◦ C) states. The hexagonal (h)-AlN formation in cubic (c)-TixAl0.37Cr1−0.37−xN (x = 0.03 and 0.16) was analyzed by in-situ x-ray scattering during annealing. The energy for h-AlN formation was found to be dependent on the microstructure evolution during annealing, which varies with the coating composition.High Al content h-ZrAlN/c-TiN and h-ZrAlN/c-ZrN multilayers were investigated through scratch tests followed by focused ion-beam analysis of the crack propagation. A c-Ti(Zr)N phase forms in h-ZrAlN/c-TiN multilayers at high temperatures and that contributes to enhanced hardness and fracture toughness by keeping the semi-coherent sub-interfaces.Finally, an in-situ analysis of coatings by x-ray scattering during a turning process was carried out. It demonstrates the possibility of observation of stress evolution and thermal expansion of the coatings or the work piece material during machining. This experiment provides real-time information on the coating behavior during cutting.
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