6,964 research outputs found
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is the most common type of leukemia. The Cancer Genome Atlas Research Network has demonstrated the increasing genomic complexity of acute myeloid leukemia (AML). In addition, the network has facilitated our understanding of the molecular events leading to this deadly form of malignancy for which the prognosis has not improved over past decades. AML is a highly heterogeneous disease, and cytogenetics and molecular analysis of the various chromosome aberrations including deletions, duplications, aneuploidy, balanced reciprocal translocations and fusion of transcription factor genes and tyrosine kinases has led to better understanding and identification of subgroups of AML with different prognoses. Furthermore, molecular classification based on mRNA expression profiling has facilitated identification of novel subclasses and defined high-, poor-risk AML based on specific molecular signatures. However, despite increased understanding of AML genetics, the outcome for AML patients whose number is likely to rise as the population ages, has not changed significantly. Until it does, further investigation of the genomic complexity of the disease and advances in drug development are needed. In this review, leading AML clinicians and research investigators provide an up-to-date understanding of the molecular biology of the disease addressing advances in diagnosis, classification, prognostication and therapeutic strategies that may have significant promise and impact on overall patient survival
The future of laboratory medicine - A 2014 perspective.
Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine
Clinical exome performance for reporting secondary genetic findings.
BACKGROUND
:
Reporting clinically actionable incidental
genetic findings in the course of clinical exome testing is
recommended by the American College of Medical Genet-
ics and Genomics (ACMG). However, the performance of
clinical exome methods for reporting small subsets of genes
has not been previously reported.
METHODS
:
In this study, 57 exome data sets performed as
clinical (n
!
12) or research (n
!
45) tests were retrospec-
tively analyzed. Exome sequencing data was examined for
adequacy in the detection of potentially pathogenic variant
locations in the 56 genes described in the ACMG incidental
findings recommendation. All exons of the 56 genes were
examined for adequacy of sequencing coverage. In addition,
nucleotide positions annotated in HGMD (Human Gene
Mutation Database) were examined.
RESULTS
:
The 56 ACMG genes have 18336 nucleotide
variants annotated in HGMD. None of the 57 exome
data sets possessed a HGMD variant. The clinical exome
test had inadequate coverage for
"
50% of HGMD vari-
ant locations in 7 genes. Six exons from 6 different genes
had consistent failure across all 3 test methods; these
exons had high GC content (76%â84%).
CONCLUSIONS
:
The use of clinical exome sequencing
for the interpretation and reporting of subsets of genes
requires recognition of the substantial possibility of
inadequate depth and breadth of sequencing coverage
at clinically relevant locations. Inadequate depth of
coverage may contribute to false-negative clinical ex-
ome results
Finite element simulation of powder compaction via shock consolidation using gas-gun system
Shock consolidation is a promising method for consolidation of nanocrystalline metallic powders since it can prevent grain growth of nanopowders during the process due to very short processing time. However, internal cracks often occurs in powder compacts during the shock consolidation process. In this paper, finite element simulations showed that reflected tensile wave causes spall phenomena resulting internal crack of powder compaction during shock compaction process. To reduce spall phenomena, FEM simulation with changing compaction die's geometry was performed to find out relationship between shape and tensile wave intensity. Based on FEM results, new compaction die was designed and bulk nanocrystalline Cu are obtained using new compaction die. (C) 2014 Published by Elsevier Ltd.open1111Ysciescopu
Does Scientific Progress Consist in Increasing Knowledge or Understanding?
Bird argues that scientific progress consists in increasing knowledge. DellsĂ©n objects that increasing knowledge is neither necessary nor sufficient for scientific progress, and argues that scientific progress rather consists in increasing understanding. DellsĂ©n also contends that unlike Birdâs view, his view can account for the scientific practices of using idealizations and of choosing simple theories over complex ones. I argue that DellsĂ©nâs criticisms against Birdâs view fail, and that increasing understanding cannot account for scientific progress, if acceptance, as opposed to belief, is required for scientific understanding
Human skeletal muscle nitrate store: influence of dietary nitrate supplementation and exercise
This is the final version. Available on open access from Wiley via the DOI in this recordRodent skeletal muscle contains a large store of nitrate that can be augmented by the consumption of dietary nitrate. This muscle nitrate reservoir has been found to be an important source of nitrite and nitric oxide (NO), via its reduction by tissue xanthine oxidoreductases (XOR). To explore if this pathway is also active in human skeletal muscle during exercise, and if it is sensitive to local nitrate availability, we assessed exercise-induced changes in muscle nitrate and nitrite concentrations in young healthy humans, under baseline conditions and following dietary nitrate consumption. We found that baseline nitrate and nitrite concentrations were far higher in muscle than in plasma (âŒ4-fold and âŒ29-fold, respectively), and that the consumption of a single bolus of dietary nitrate (12.8 mmol) significantly elevated nitrate concentration in both plasma (âŒ19 fold) and muscle (âŒ5 fold). Consistent with these observations, and with previous suggestions of active muscle nitrate transport, we present Western blot data to show significant expression of the active nitrate/nitrite transporter, sialin, in human skeletal muscle. Furthermore, we report an exercise-induced reduction in human muscle nitrate concentration (by âŒ39%), but only in the presence of an increased muscle nitrate store. Our results indicate that human skeletal muscle nitrate stores are sensitive to dietary nitrate intake and may contribute to NO generation during exercise. Together, these findings suggest that skeletal muscle plays an important role in the transport, storage and metabolism of nitrate in humans. This article is protected by copyright. All rights reserved
Recognition of cancer warning signs and anticipated time to help-seeking in a population sample of adults in the UK
Background: Not recognising a symptom as suspicious is a common reason given by cancer patients for delayed help-seeking; but inevitably this is retrospective. We therefore investigated associations between recognition of warning signs for breast, colorectal and lung cancer and anticipated time to help-seeking for symptoms of each cancer.
Methods: Computer-assisted telephone interviews were conducted with a population-representative sample (N=6965) of UK adults age greater than or equal to50 years, using the Awareness and Beliefs about Cancer scale. Anticipated time to help-seeking for persistent cough, rectal bleeding and breast changes was categorised as >2 vs less than or equal to2 weeks. Recognition of persistent cough, unexplained bleeding and unexplained lump as cancer warning signs was assessed (yes/no). Associations between recognition and help-seeking were examined for each symptom controlling for demographics and perceived ease of health-care access.
Results: For each symptom, the odds of waiting for >2 weeks were significantly increased in those who did not recognise the related warning sign: breast changes: OR=2.45, 95% CI 1.47â4.08; rectal bleeding: OR=1.77, 1.36â2.30; persistent cough: OR=1.30, 1.17â1.46, independent of demographics and health-care access.
Conclusion: Recognition of warning signs was associated with anticipating faster help-seeking for potential symptoms of cancer. Strategies to improve recognition are likely to facilitate earlier diagnosis
Electro-optically tunable microring resonators in lithium niobate
Optical microresonators have recently attracted a growing attention in the
photonics community. Their applications range from quantum electro-dynamics to
sensors and filtering devices for optical telecommunication systems, where they
are likely to become an essential building block. The integration of nonlinear
and electro-optical properties in the resonators represents a very stimulating
challenge, as it would incorporate new and more advanced functionality. Lithium
niobate is an excellent candidate material, being an established choice for
electro-optic and nonlinear optical applications. Here we report on the first
realization of optical microring resonators in submicrometric thin films of
lithium niobate. The high index contrast films are produced by an improved
crystal ion slicing and bonding technique using benzocyclobutene. The rings
have radius R=100 um and their transmission spectrum has been tuned using the
electro-optic effect. These results open new perspectives for the use of
lithium niobate in chip-scale integrated optical devices and nonlinear optical
microcavities.Comment: 15 pages, 8 figure
Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies
PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Particle-in-cell simulations of rf breakdown
Breakdown voltages of a capacitively coupled radio frequency argon discharge
at 27 MHz are studied. We use a one-dimensional electrostatic PIC code to
investigate the effect of changing the secondary emission properties of the
electrodes on the breakdown voltage, particularly at low pd values. Simulation
results are compared with the available experimental results and a satisfactory
agreement is found.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004,
Nice (France
- âŠ