Diagnostic performance of breast tumor tissue selection in diffusion weighted imaging:A systematic review and meta-analysis

Background Several methods for tumor delineation are used in literature on breast diffusion weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC). However, in the process of reaching consensus on breast DWI scanning protocol, image analysis and interpretation, still no standardized optimal breast tumor tissue selection (BTTS) method exists. Therefore, the purpose of this study is to assess the impact of BTTS methods on ADC in the discrimination of benign from malignant breast lesions in DWI in terms of sensitivity, specificity and area under the curve (AUC). Methods and findings In this systematic review and meta-analysis, adhering to the PRISMA statement, 61 studies, with 65 study subsets, in females with benign or malignant primary breast lesions (6291 lesions) were assessed. Studies on DWI, quantified by ADC, scanned on 1.5 and 3.0 Tesla and using b-values 0/50 and >= 800 s/mm(2) were included. PubMed and EMBASE were searched for studies up to 23-10-2019 (n = 2897). Data were pooled based on four BTTS methods (by definition of measured region of interest, ROI): BTTS1: whole breast tumor tissue selection, BTTS2: subtracted whole breast tumor tissue selection, BTTS3: circular breast tumor tissue selection and BTTS4: lowest diffusion breast tumor tissue selection. BTTS methods 2 and 3 excluded necrotic, cystic and hemorrhagic areas. Pooled sensitivity, specificity and AUC of the BTTS methods were calculated. Heterogeneity was explored using the inconsistency index (I-2) and considering covariables: field strength, lowest b-value, image of BTTS selection, pre-or post-contrast DWI, slice thickness and ADC threshold. Pooled sensitivity, specificity and AUC were: 0.82 (0.72-0.89), 0.79 (0.65-0.89), 0.88 (0.85-0.90) for BTTS1; 0.91 (0.89-0.93), 0.84 (0.80-0.87), 0.94 (0.91-0.96) for BTTS2; 0.89 (0.86-0.92), 0.90 (0.85-0.93), 0.95 (0.93-0.96) for BTTS3 and 0.90 (0.86-0.93), 0.84 (0.81-0.87), 0.86 (0.82-0.88) for BTTS4, respectively. Significant heterogeneity was found between studies (I-2 = 95). Conclusions None of the breast tissue selection (BTTS) methodologies outperformed in differentiating benign from malignant breast lesions. The high heterogeneity of ADC data acquisition demands further standardization, such as DWI acquisition parameters and tumor tissue selection to substantially increase the reliability of DWI of the breast

Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI)

Breast density is an independent risk factor for the development of breast cancer and also decreases the sensitivity of mammography for screening. Consequently, women with extremely dense breasts face an increased risk of late diagnosis of breast cancer. These women are, therefore, underserved with current mammographic screening programs. The results of recent studies reporting on contrast-enhanced breast MRI as a screening method in women with extremely dense breasts provide compelling evidence that this approach can enable an important reduction in breast cancer mortality for these women and is cost-effective. Because there is now a valid option to improve breast cancer screening, the European Society of Breast Imaging (EUSOBI) recommends that women should be informed about their breast density. EUSOBI thus calls on all providers of mammography screening to share density information with the women being screened. In light of the available evidence, in women aged 50 to 70 years with extremely dense breasts, the EUSOBI now recommends offering screening breast MRI every 2 to 4 years. The EUSOBI acknowledges that it may currently not be possible to offer breast MRI immediately and everywhere and underscores that quality assurance procedures need to be established, but urges radiological societies and policymakers to act on this now. Since the wishes and values of individual women differ, in screening the principles of shared decision-making should be embraced. In particular, women should be counselled on the benefits and risks of mammography and MRI-based screening, so that they are capable of making an informed choice about their preferred screening method

Relaxor ferroelectricity and colossal magnetocapacitive coupling in ferromagnetic CdCr2S4

Multiferroic materials, which reveal magnetic and electric order, are in the focus of recent solid state research. Especially the simultaneous occurrence of ferroelectricity and ferromagnetism, combined with an intimate coupling of magnetization and polarization via magneto-capacitive effects, could pave the way for a new generation of electronic devices. Here we present measurements on a simple cubic spinel with unusual properties: It shows ferromagnetic order and simultaneously relaxor ferroelectricity, i.e. a ferroelectric cluster state, reached by a smeared-out phase transition, both with sizable ordering temperatures and moments. Close to the ferromagnetic ordering temperature the magneto-capacitive coupling, characterized by a variation of the dielectric constant in an external magnetic field, reaches colossal values of nearly 500%. We attribute the relaxor properties to geometric frustration, which is well known for magnetic moments, but here is found to impede long-range order of the structural degrees of freedom.Comment: 4 pages, 3 figure

Equivalence of plasma p-tau217 with cerebrospinal fluid in the diagnosis of Alzheimer's disease

INTRODUCTION: Plasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established biomarkers are needed. METHODS: We assessed the diagnostic performance of p-tau181, p-tau217, and p-tau231 in plasma and CSF in 174 individuals evaluated by dementia specialists and assessed with amyloid-PET and tau-PET. Receiver operating characteristic (ROC) analyses assessed the performance of plasma and CSF biomarkers to identify amyloid-PET and tau-PET positivity. RESULTS: Plasma p-tau biomarkers had lower dynamic ranges and effect sizes compared to CSF p-tau. Plasma p-tau181 (AUC = 76%) and p-tau231 (AUC = 82%) assessments performed inferior to CSF p-tau181 (AUC = 87%) and p-tau231 (AUC = 95%) for amyloid-PET positivity. However, plasma p-tau217 (AUC = 91%) had diagnostic performance indistinguishable from CSF (AUC = 94%) for amyloid-PET positivity. DISCUSSION: Plasma and CSF p-tau217 had equivalent diagnostic performance for biomarker-defined AD. Our results suggest that plasma p-tau217 may help reduce the need for invasive lumbar punctures without compromising accuracy in the identification of AD. Highlights: p-tau217 in plasma performed equivalent to p-tau217 in CSF for the diagnosis of AD, suggesting the increased accessibility of plasma p-tau217 is not offset by lower accuracy. p-tau biomarkers in plasma had lower mean fold-changes between amyloid-PET negative and positive groups than p-tau biomarkers in CSF. CSF p-tau biomarkers had greater effect sizes than plasma p-tau biomarkers when differentiating between amyloid-PET positive and negative groups. Plasma p-tau181 and plasma p-tau231 performed worse than p-tau181 and p-tau231 in CSF for AD diagnosis

Do differences in understory light contribute to species distributions along a tropical rainfall gradient?

In tropical forests, regional differences in annual rainfall correlate with differences in plant species composition. Although water availability is clearly one factor determining species distribution, other environmental variables that covary with rainfall may contribute to distributions. One such variable is light availability in the understory, which decreases towards wetter forests due to differences in canopy density and phenology. We established common garden experiments in three sites along a rainfall gradient across the Isthmus of Panama in order to measure the differences in understory light availability, and to evaluate their influence on the performance of 24 shade-tolerant species with contrasting distributions. Within sites, the effect of understory light availability on species performance depended strongly on water availability. When water was not limiting, either naturally in the wetter site or through water supplementation in drier sites, seedling performance improved at higher light. In contrast, when water was limiting at the drier sites, seedling performance was reduced at higher light, presumably due to an increase in water stress that affected mostly wet-distribution species. Although wetter forest understories were on average darker, wet-distribution species were not more shade-tolerant than dry-distribution species. Instead, wet-distribution species had higher absolute growth rates and, when water was not limiting, were better able to take advantage of small increases in light than dry-distribution species. Our results suggest that in wet forests the ability to grow fast during temporary increases in light may be a key trait for successful recruitment. The slower growth rates of the dry-distribution species, possibly due to trade-offs associated with greater drought tolerance, may exclude these species from wetter forests

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Computer-aided detection in breast MRI: a systematic review and meta-analysis

To evaluate the additional value of computer-aided detection (CAD) in breast MRI by assessing radiologists' accuracy in discriminating benign from malignant breast lesions. A literature search was performed with inclusion of relevant studies using a commercially available CAD system with automatic colour mapping. Two independent researchers assessed the quality of the studies. The accuracy of the radiologists' performance with and without CAD was presented as pooled sensitivity and specificity. Of 587 articles, 10 met the inclusion criteria, all of good methodological quality. Experienced radiologists reached comparable pooled sensitivity and specificity before and after using CAD (sensitivity: without CAD: 89%; 95% CI: 78-94%, with CAD: 89%; 95%CI: 81-94%) (specificity: without CAD: 86%; 95% CI: 79-91%, with CAD: 82%; 95% CI: 76-87%). For residents the pooled sensitivity increased from 72% (95% CI: 62-81%) without CAD to 89% (95% CI: 80-94%) with CAD, however, not significantly. Concerning specificity, the results were similar (without CAD: 79%; 95% CI: 69-86%, with CAD: 78%; 95% CI: 69-84%). CAD in breast MRI has little influence on the sensitivity and specificity of experienced radiologists and therefore their interpretation remains essential. However, residents or inexperienced radiologists seem to benefit from CAD concerning breast MRI evaluation

Multiplex Immunoassay of Lower Genital Tract Mucosal Fluid from Women Attending an Urban STD Clinic Shows Broadly Increased IL1ß and Lactoferrin

BACKGROUND: More than one million new cases of sexually transmitted diseases (STDs) occur each day. The immune responses and inflammation induced by STDs and other frequent non-STD microbial colonizations (i.e. Candida and bacterial vaginosis) can have serious pathologic consequences in women including adverse pregnancy outcomes, infertility and increased susceptibility to infection by other pathogens. Understanding the types of immune mediators that are elicited in the lower genital tract by these infections/colonizations can give important insights into the innate and adaptive immune pathways that are activated and lead to strategies for preventing pathologic effects. METHODOLOGY/PRINCIPAL FINDINGS: 32 immune mediators were measured by multiplexed immunoassays to assess the immune environment of the lower genital tract mucosa in 84 women attending an urban STD clinic. IL-3, IL-1ß, VEGF, angiogenin, IL-8, ß2Defensin and ß3Defensin were detected in all subjects, Interferon-α was detected in none, while the remaining mediators were detected in 40% to 93% of subjects. Angiogenin, VEGF, FGF, IL-9, IL-7, lymphotoxin-α and IL-3 had not been previously reported in genital mucosal fluid from women. Strong correlations were observed between levels of TNF-α, IL-1ß and IL-6, between chemokines IP-10 and MIG and between myeloperoxidase, IL-8 and G-CSF. Samples from women with any STD/colonization had significantly higher levels of IL-8, IL-3, IL-7, IL-1ß, lactoferrin and myeloperoxidase. IL-1ß and lactoferrin were significantly increased in gonorrhea, Chlamydia, cervicitis, bacterial vaginosis and trichomoniasis. CONCLUSIONS/SIGNIFICANCE: These studies show that mucosal fluid in general appears to be an environment that is rich in immune mediators. Importantly, IL-1ß and lactoferrin are biomarkers for STDs/colonizations providing insights into immune responses and pathogenesis at this mucosal site

Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein

Background: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase)™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses. Methods and Findings: The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus. Conclusions: The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV.published_or_final_versio