Tumour-derived extracellular vesicles in blood of metastatic cancer patients associate with overall survival

Background: Circulating tumour cells (CTCs) in blood associate with overall survival (OS) of cancer patients, but they are detected in extremely low numbers. Large tumour-derived extracellular vesicles (tdEVs) in castration-resistant prostate cancer (CRPC) patients are present at around 20 times higher frequencies than CTCs and have equivalent prognostic power. In this study, we explored the presence of tdEVs in other cancers and their association with OS. Methods: The open-source ACCEPT software was used to automatically enumerate tdEVs in digitally stored CellSearch® images obtained from previously reported CTC studies evaluating OS in 190 CRPC, 450 metastatic colorectal cancer (mCRC), 179 metastatic breast cancer (MBC) and 137 non-small cell lung cancer (NSCLC) patients before the initiation of a new treatment. Results: Presence of unfavourable CTCs and tdEVs is predictive of OS, with respective hazard ratios (HRs) of 2.4 and 2.2 in CRPC, 2.7 and 2.2 in MBC, 2.3 and 1.9 in mCRC and 2.0 and 2.4 in NSCLC, respectively. Conclusions: tdEVs have equivalent prognostic value as CTCs in the investigated metastatic cancers. CRPC, mCRC, and MBC (but not NSCLC) patients with favourable CTC counts can be further prognostically stratified using tdEVs. Our data suggest that tdEVs could be used in clinical decision-making.</p

Origins of Diamond Surface Noise Probed by Correlating Single-Spin Measurements with Surface Spectroscopy

The nitrogen vacancy (NV) center in diamond exhibits spin-dependent fluorescence and long spin coherence times under ambient conditions, enabling applications in quantum information processing and sensing. NV centers near the surface can have strong interactions with external materials and spins, enabling new forms of nanoscale spectroscopy. However, NV spin coherence degrades within 100 nanometers of the surface, suggesting that diamond surfaces are plagued with ubiquitous defects. Prior work on characterizing near-surface noise has primarily relied on using NV centers themselves as probes; while this has the advantage of exquisite sensitivity, it provides only indirect information about the origin of the noise. Here we demonstrate that surface spectroscopy methods and single spin measurements can be used as complementary diagnostics to understand sources of noise. We find that surface morphology is crucial for realizing reproducible chemical termination, and use these insights to achieve a highly ordered, oxygen-terminated surface with suppressed noise. We observe NV centers within 10 nm of the surface with coherence times extended by an order of magnitude

Effective theory of the Delta(1232) in Compton scattering off the nucleon

We formulate a new power-counting scheme for a chiral effective field theory of nucleons, pions, and Deltas. This extends chiral perturbation theory into the Delta-resonance region. We calculate nucleon Compton scattering up to next-to-leading order in this theory. The resultant description of existing $\gamma$p cross section data is very good for photon energies up to about 300 MeV. We also find reasonable numbers for the spin-independent polarizabilities $\alpha_p$ and $\beta_p$.Comment: 29 pp, 9 figs. Minor revisions. To be published in PR

ALG: Automated Genotype Calling of Luminex Assays

Single nucleotide polymorphisms (SNPs) are the most commonly used polymorphic markers in genetics studies. Among the different platforms for SNP genotyping, Luminex is one of the less exploited mainly due to the lack of a robust (semi-automated and replicable) freely available genotype calling software. Here we describe a clustering algorithm that provides automated SNP calls for Luminex genotyping assays. We genotyped 3 SNPs in a cohort of 330 childhood leukemia patients, 200 parents of patient and 325 healthy individuals and used the Automated Luminex Genotyping (ALG) algorithm for SNP calling. ALG genotypes were called twice to test for reproducibility and were compared to sequencing data to test for accuracy. Globally, this analysis demonstrates the accuracy (99.6%) of the method, its reproducibility (99.8%) and the low level of no genotyping calls (3.4%). The high efficiency of the method proves that ALG is a suitable alternative to the current commercial software. ALG is semi-automated, and provides numerical measures of confidence for each SNP called, as well as an effective graphical plot. Moreover ALG can be used either through a graphical user interface, requiring no specific informatics knowledge, or through command line with access to the open source code. The ALG software has been implemented in R and is freely available for non-commercial use either at http://alg.sourceforge.net or by request to [email protected]

Probing the physics of the solar atmosphere with the Multi-slit Solar Explorer (MUSE). I. Coronal heating

Funding: I.D.M. has received support from the UK Science and Technology Facilities Council (Consolidated grant ST/K000950/1), the European Union Horizon 2020 research and innovation program (grant agreement No. 647214), and the Research Council of Norway through its Centres of Excellence scheme, project number 262622.The Multi-slit Solar Explorer (MUSE) is a proposed mission composed of a multislit extreme ultraviolet (EUV) spectrograph (in three spectral bands around 171 Å, 284 Å, and 108 Å) and an EUV context imager (in two passbands around 195 Å and 304 Å). MUSE will provide unprecedented spectral and imaging diagnostics of the solar corona at high spatial (≤0.″5) and temporal resolution (down to ∼0.5 s for sit-and-stare observations), thanks to its innovative multislit design. By obtaining spectra in four bright EUV lines (Fe ix 171 Å, Fe xv 284 Å, Fe xix–Fe xxi 108 Å) covering a wide range of transition regions and coronal temperatures along 37 slits simultaneously, MUSE will, for the first time, “freeze” (at a cadence as short as 10 s) with a spectroscopic raster the evolution of the dynamic coronal plasma over a wide range of scales: from the spatial scales on which energy is released (≤0.″5) to the large-scale (∼170″ × 170″) atmospheric response. We use numerical modeling to showcase how MUSE will constrain the properties of the solar atmosphere on spatiotemporal scales (≤0.″5, ≤20 s) and the large field of view on which state-of-the-art models of the physical processes that drive coronal heating, flares, and coronal mass ejections (CMEs) make distinguishing and testable predictions. We describe the synergy between MUSE, the single-slit, high-resolution Solar-C EUVST spectrograph, and ground-based observatories (DKIST and others), and the critical role MUSE plays because of the multiscale nature of the physical processes involved. In this first paper, we focus on coronal heating mechanisms. An accompanying paper focuses on flares and CMEs.Publisher PDFPeer reviewe

Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: Study design

Background: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. Methods/Design: This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived =8years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses. Discussion: Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors. Trial registration: Registered at the Dutch Trial Registry (NTR): NTR4961

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations