Contrast-enhanced MRI for breast cancer screening

Contains fulltext : 208984.pdf (publisher's version ) (Open Access)Multiple studies in the first decade of the 21(st) century have established contrast-enhanced breast MRI as a screening modality for women with a hereditary or familial increased risk for the development of breast cancer. In recent studies, in women with various risk profiles, the sensitivity ranges between 81% and 100%, which is approximately twice as high as the sensitivity of mammography. The specificity increases in follow-up rounds to around 97%, with positive predictive values for biopsy in the same range as for mammography. MRI preferentially detects the more aggressive/invasive types of breast cancer, but has a higher sensitivity than mammography for any type of cancer. This performance implies that in women screened with breast MRI, all other examinations must be regarded as supplemental. Mammography may yield ~5% additional cancers, mostly ductal carcinoma in situ, while slightly decreasing specificity and increasing the costs. Ultrasound has no supplemental value when MRI is used. Evidence is mounting that in other groups of women the performance of MRI is likewise superior to more conventional screening techniques. Particularly in women with a personal history of breast cancer, the gain seems to be high, but also in women with a biopsy history of lobular carcinoma in situ and even women at average risk, similar results are reported. Initial outcome studies show that breast MRI detects cancer earlier, which induces a stage-shift increasing the survival benefit of screening. Cost-effectiveness is still an issue, particularly for women at lower risk. Since costs of the MRI scan itself are a driving factor, efforts to reduce these costs are essential. The use of abbreviated MRI protocols may enable more widespread use of breast MRI for screening. Level of Evidence: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:377-390

Spinning Black Holes in (2+1)-dimensional String and Dilaton Gravity

We present a new class of spinning black hole solutions in $(2+1)$-dimensional general relativity minimally coupled to a dilaton with potential $e^{b\phi}\Lambda$. When $b=4$, the corresponding spinning black hole is a solution of low energy $(2+1)$-dimensional string gravity. Apart from the limiting case of the $BTZ$ black hole, these spinning black holes have no inner horizon and a curvature singularity only at the origin. We compute the mass and angular momentum parameters of the solutions at spatial infinity, as well as their temperature and entropy.Comment: 8 pages, Latex, statements about mass of 2+1 Hirschmann and Welch magnetic solution corrected, in press in Phys. Lett.

Charged Dilaton Black Holes with Unusual Asymptotics

We present a new class of black hole solutions in Einstein-Maxwell-dilaton gravity in $n \ge 4$ dimensions. These solutions have regular horizons and a singularity only at the origin. Their asymptotic behavior is neither asymptotically flat nor (anti-) de Sitter. Similar solutions exist for certain Liouville-type potentials for the dilaton.Comment: 24 pages, harvmac.tex, no figure

Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3–6 months' observation using advanced image analysis of 3T MRI?

SummaryPurposePrior investigations of magnetic resonance imaging (MRI) biomarkers of cartilage loss in knee osteoarthritis (OA) suggest that trials of interventions which affect this biomarker with adequate statistical power would require large clinical studies of 1–2 years duration. We hypothesized that smaller, shorter duration, “Proof of Concept” (PoC) studies might be achievable by: (1) selecting a population at high risk of rapid medial tibio-femoral (TF) progression, in conjunction with; (2) high-field MRI (3T), and; (3) using advanced image analysis. The primary outcome was the cartilage thickness in the central medial femur.MethodsMulti-centre, non-randomized, observational cohort study at four sites in the US. Eligible participants were females with knee pain, a body mass index (BMI)≥25kg/m2, symptomatic radiographic evidence of medial TF OA, and varus mal-alignment. The 29 participants had a mean age of 62 years, mean BMI of 36kg/m2, with eight index knees graded as Kellgren–Lawrence (K&L)=2 and 21 as K&L=3. Eligible participants had four MRI scans of one knee: two MRIs (1 week apart) were acquired as a baseline with follow-up MRI at 3 and 6 months. A trained operator, blind to time-point but not subject, manually segmented the cartilage from the Dual Echo Steady State water excitation MR images. Anatomically corresponding regions of interest were identified on each image by using a three-dimensional statistical shape model of the endosteal bone surface, and the cartilage thickness (with areas denuded of cartilage included as having zero thickness – ThCtAB) within each region was calculated. The percentage change from baseline at 3 and 6 months was assessed using a log-scale analysis of variance (ANOVA) model including baseline as a covariate. The primary outcome was the change in cartilage thickness within the aspect of central medial femoral condyle exposed within the meniscal window (w) during articulation, neglecting cartilage edges [nuclear (n)] (nwcMF·ThCtAB), with changes in other regions considered as secondary endpoints.ResultsAnatomical mal-alignment ranged from −1.9° to 6.3°, with mean 0.9°. With one exception, no changes in ThCtAB were detected at the 5% level for any of the regions of interest on the TF joint at 3 or 6 months of follow-up. The change in the primary variable (nwcMF·ThCtAB) from (mean) baseline at 3 months from the log-scale ANOVA model was −2.1% [95% confidence interval (CI) (−4.4%, +0.2%)]. The change over 6 months was 0.0% [95% CI (−2.7%, +2.8%)]. The 95% CI for the change from baseline did not include zero for the cartilage thickness within the meniscal window of the lateral tibia (wLT·ThCtAB) at 6 month follow-up (−1.5%, 95% CI [−2.9, −0.2]), but was not significant at the 5% level after correction for multiple comparisons.ConclusionsThe small inconsistent compartment changes, and the relatively high variabilities in cartilage thickness changes seen over time in this study, provide no additional confidence for a 3- or 6-month PoC study using a patient population selected on the basis of risk for rapid progression with the MRI acquisition and analyses employed

Multiorder coherent Raman scattering of a quantum probe field

We study the multiorder coherent Raman scattering of a quantum probe field in a far-off-resonance medium with a prepared coherence. Under the conditions of negligible dispersion and limited bandwidth, we derive a Bessel-function solution for the sideband field operators. We analytically and numerically calculate various quantum statistical characteristics of the sideband fields. We show that the multiorder coherent Raman process can replicate the statistical properties of a single-mode quantum probe field into a broad comb of generated Raman sidebands. We also study the mixing and modulation of photon statistical properties in the case of two-mode input. We show that the prepared Raman coherence and the medium length can be used as control parameters to switch a sideband field from one type of photon statistics to another type, or from a non-squeezed state to a squeezed state and vice versa.Comment: 12 pages, 7 figures, to be published in Phys. Rev.

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalmic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review resulsts from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73437/1/j.1749-6632.1997.tb52357.x.pd

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Toward a Multifaceted Heuristic of Digital Reading to Inform Assessment, Research, Practice, and Policy

In this commentary, the author explores the tension between almost 30 years of work that has embraced increasingly complex conceptions of digital reading and recent studies that risk oversimplifying digital reading as a singular entity analogous with reading text on a screen. The author begins by tracing a line of theoretical and empirical work that both informs and complicates our understanding of digital literacy and, more specifically, digital reading. Then, a heuristic is proposed to systematically organize, label, and define a multifaceted set of increasingly complex terms, concepts, and practices that characterize the spectrum of digital reading experiences. Research that informs this heuristic is used to illustrate how more precision in defining digital reading can promote greater clarity across research methods and advance a more systematic study of promising digital reading practices. Finally, the author discusses implications for assessment, research, practice, and policy

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy