1,561 research outputs found
Recommended from our members
Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival.
PurposeGenomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes.Patients and methodsNext-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer.ResultsMost patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% (APC) to 85.5% (BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response (P = .045); progression-free survival, 6.1 versus 2.3 months (P = .08); and survival not reached versus 9.4 months (P = .146; all by multivariable analysis).ConclusionPatients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation
Anisotropic Aerogels for Studying Superfluid He
It may be possible to stabilize new superfluid phases of He with
anisotropic silica aerogels. We discuss two methods that introduce anisotropy
in the aerogel on length scales relevant to superfluid He. First,
anisotropy can be induced with uniaxial strain. A second method generates
anisotropy during the growth and drying stages. We have grown cylindrical
98% aerogels with anisotropy indicated by preferential radial shrinkage
after supercritical drying and find that this shrinkage correlates with small
angle x-ray scattering (SAXS). The growth-induced anisotropy was found to be
out of phase relative to that induced by strain. This has
implications for the possible stabilization of superfluid phases with specific
symmetry.Comment: 6 pages, 4 figures, submitted to Quantum Fluids and Solids (QFS)
conference 200
Recommended from our members
Revisiting Epidermal Growth Factor Receptor (EGFR) Amplification as a Target for Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor DNA in Patients With Advanced Malignancies.
PurposeTo date, evidence for tissue epidermal growth factor receptor (EGFR) overexpression as a biomarker for anti-EGFR therapies has been weak. We investigated the genomic landscape of EGFR amplification in blood-derived cell-free tumor DNA (cfDNA) across diverse cancers and the role of anti-EGFR therapies in achieving response.MethodsWe assessed EGFR amplification status among 28,584 patients with malignancies evaluated by clinical-grade next-generation sequencing (NGS) of blood-derived cfDNA (54- to 73-gene panel). Furthermore, we curated the clinical characteristics of 1,434 patients at the University of California San Diego who had cfDNA testing by this NGS test.ResultsOverall, EGFR amplification was detected in cfDNA from 8.5% of patients (2,423 of 28,584), most commonly in colorectal (16.3% [458 of 2,807]), non-small-cell lung (9.0% [1,096 of 12,197]), and genitourinary cancers (8.1% [170 of 2,104]). Most patients had genomic coalterations (96.9% [95 of 98]), frequently involving genes affecting other tyrosine kinases (72.4% [71 of 98]), mitogen-activated protein kinase cascades (56.1% [55 of 98]), cell-cycle-associated signals (52.0% [51 of 98]), and the phosphoinositide 3-kinase pathway (35.7% [35 of 98]). EGFR amplification emerged in serial cfDNA after various anticancer therapies (n = 6), including checkpoint inhibitors (n = 4), suggesting a possible role for these amplifications in acquired resistance. Nine evaluable patients with EGFR amplification were treated with anti-EGFR-based regimens; five (55.6%) achieved partial responses, including three patients whose tissue NGS lacked EGFR amplification.ConclusionEGFR amplification was detected in cfDNA among 8.5% of 28,584 diverse cancers. Most patients had coexisting alterations. Responses were observed in five of nine patients who received EGFR inhibitors. Incorporating EGFR inhibitors into the treatment regimens of patients harboring EGFR amplification in cfDNA merits additional study
Development, Implementation and Evaluation of a Peer Review of Teaching (PRoT) Initiative in Nursing Education
For many years, an area of research in higher education has been emerging around the development and implementation of fair and effective peer evaluation programs. Recently, a new body of knowledge has developed regarding the development and implementation of fair and effective peer evaluation programs resulting in formative and summative evaluations. The purpose of this article is to describe the development, implementation, and evaluation of a peer review of teaching (PRoT) program for nursing faculty, initiated at one small comprehensive university in the northeastern United States. Pairs of nursing faculty evaluated each other’s teaching, syllabi, and course materials after collaborating in a pre-evaluation conference to discuss goals of the classroom visit. Qualitative data gathered in post project focus groups revealed that faculty found their modified PRoT process to be a mutually beneficial experience that was more useful, flexible and collegial, and less stressful than their previous evaluation process
Magnetoresistance of UPt3
We have performed measurements of the temperature dependence of the
magnetoresistance up to 9 T in bulk single crystals of UPt3 with the magnetic
field along the b axis, the easy magnetization axis. We have confirmed previous
results for transverse magnetoresistance with the current along the c axis, and
report measurements of the longitudinal magnetoresistance with the current
along the b axis. The presence of a linear term in both cases indicates broken
orientational symmetry associated with magnetic order. With the current along
the c axis the linear term appears near 5 K, increasing rapidly with decreasing
temperature. For current along the b axis the linear contribution is negative.Comment: 6 pages, 3 figures, submitted to Quantum Fluids and Solids Conference
(QFS 2006
Development, Implementation and Evaluation of a Peer Review of Teaching (PRoT) Initiative in Nursing Education
For many years, an area of research in higher education has been emerging around the development and implementation of fair and effective peer evaluation programs. Recently, a new body of knowledge has developed regarding the development and implementation of fair and effective peer evaluation programs resulting in formative and summative evaluations. The purpose of this article is to describe the development, implementation, and evaluation of a peer review of teaching (PRoT) program for nursing faculty, initiated at one small comprehensive university in the northeastern United States. Pairs of nursing faculty evaluated each other’s teaching, syllabi, and course materials after collaborating in a pre-evaluation conference to discuss goals of the classroom visit. Qualitative data gathered in post project focus groups revealed that faculty found their modified PRoT process to be a mutually beneficial experience that was more useful, flexible and collegial, and less stressful than their previous evaluation process
Differential regulation of a MYB transcription factor is correlated with transgenerational epigenetic inheritance of trichome density in Mimulus guttatus
This is the peer reviewed version of the following article: Scoville, A. G., Barnett, L. L., Bodbyl-Roels, S., Kelly, J. K. and Hileman, L. C. (2011), Differential regulation of a MYB transcription factor is correlated with transgenerational epigenetic inheritance of trichome density in Mimulus guttatus. New Phytologist, 191: 251–263. doi:10.1111/j.1469-8137.2011.03656.x, which has been published in final form at http://doi.org/10.1111/j.1469-8137.2011.03656.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Epigenetic inheritance, transgenerational transmission of traits not proximally determined by DNA sequence, has been linked to transmission of chromatin modifications and gene regulation, which are known to be sensitive to environmental factors. Mimulus guttatus increases trichome (plant hair) density in response to simulated herbivore damage. Increased density is expressed in progeny even if progeny do not experience damage. To better understand epigenetic inheritance of trichome production, we tested the hypothesis that candidate gene expression states are inherited in response to parental damage.
Using M. guttatus recombinant inbred lines, offspring of leaf-damaged and control plants were raised without damage. Relative expression of candidate trichome development genes was measured in offspring. Line and parental damage effects on trichome density were measured. Associations between gene expression, trichome density, and response to parental damage were determined.
We identified M. guttatus MYB MIXTA-like 8 as a possible negative regulator of trichome development. We found that parental leaf damage induces down-regulation of MYB MIXTA-like 8 in progeny, which is associated with epigenetically inherited increased trichome density.
Our results link epigenetic transmission of an ecologically important trait with differential gene expression states – providing insight into a mechanism underlying environmentally induced ‘soft inheritance’
Positive Surgical Margins in the 10 Most Common Solid Cancers.
A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998-2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998-2002 and 2008-2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes
Compressed Silica Aerogels for the Study of Superfluid 3He
We have performed Small Angle X-ray Scattering (SAXS) on uniaxially strained
aerogels and measured the strain-induced structural anisotropy. We use a model
to connect our SAXS results to anisotropy of the 3He quasiparticle mean free
path in aerogel.Comment: 2 pages, 2 figures, accepted for publication in the proceedings of
the 24th Low Temperature Physics Conferenc
Interplay between magnetism and superconductivity and appearance of a second superconducting transition in alpha-FeSe at high pressure
We synthesized tetragonal alpha-FeSe by melting a powder mixture of iron and
selenium at high pressure. Subsequent annealing at normal pressure results in
removing traces of hexagonal beta- FeSe, formation of a rather sharp transition
to superconducting state at Tc ~ 7 K, and the appearance of a magnetic
transition near Tm = 120 K. Resistivity and ac-susceptibility were measured on
the annealed sample at hydrostatic pressure up to 4.5 GPa. A magnetic
transition visible in ac-susceptibility shifts down under pressure and the
resistive anomaly typical for a spin density wave (SDW) antiferromagnetic
transition develops near the susceptibility anomaly. Tc determined by the
appearance of a diamagnetic response in susceptibility, increases linearly
under pressure at a rate dTc/dP = 3.5 K/GPa. Below 1.5 GPa, the resistive
superconducting transition is sharp; the width of transition does not change
with pressure; and, Tc determined by a peak in drho/dT increases at a rate ~
3.5 K/GPa. At higher pressure, a giant broadening of the resistive transition
develops. This effect cannot be explained by possible pressure gradients in the
sample and is inherent to alpha-FeSe. The dependences drho(T)/dT show a
signature for a second peak above 3 GPa which is indicative of the appearance
of another superconducting state in alpha-FeSe at high pressure. We argue that
this second superconducting phase coexists with SDW antiferromagnetism in a
partial volume fraction and originates from pairing of charge carriers from
other sheets of the Fermi surface
- …