Early Contrast Enhancement: a novel Magnetic Resonance Imaging biomarker of pleural malignancy

Introduction: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening. Materials and methods: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma. Results: 71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61–94%), specificity 83% (95% CI 68–91%), positive predictive value 68% (95% CI 47–84%), negative predictive value 92% (78–97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02). Discussion: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted

Nfil3/E4bp4 is required for the development and maturation of NK cells in vivo

Nuclear factor interleukin-3 (Nfil3; also known as E4-binding protein 4) is a basic region leucine zipper transcription factor that has antiapoptotic activity in vitro under conditions of growth factor withdrawal. To study the role of Nfil3 in vivo, we generated gene-targeted Nfil3-deficient (Nfil3−/−) mice. Nfil3−/− mice were born at normal Mendelian frequency and were grossly normal and fertile. Although numbers of T cells, B cells, and natural killer (NK) T cells were normal in Nfil3−/− mice, a specific disruption in NK cell development resulted in severely reduced numbers of mature NK cells in the periphery. This defect was NK cell intrinsic in nature, leading to a failure to reject MHC class I–deficient cells in vivo and reductions in both interferon γ production and cytolytic activity in vitro. Our results confirm the specific and essential requirement of Nfil3 for the development of cells of the NK lineage

The Effect of the Earned Income Tax Credit in the District of Columbia on Poverty and Income Dynamics

Using unique longitudinal administrative tax panel data for the District of Columbia (DC), we assess the combined effect of the DC supplemental earned income tax credit (EITC) and the federal EITC on poverty and income dynamics within Washington, DC, from 2001 to 2011. The EITC in DC merits investigation, as the DC supplement to the federal credit is the largest in the nation. The supplemental DC EITC was enacted in 2000, and has been expanded from 10 percent of the federal credit in 2001 to 40 percent as of 2009. To implement the study, we estimate least squares models with 0/1 dependent variables to estimate the likelihood of net-EITC income above poverty and near-poverty thresholds. We also estimate the likelihood of earnings growth and income stabilization from the EITC. To identify the effect of the EITC, we exploit variation in the EITC subsidy rate from 2008 to 2009, when an additional EITC bracket of 45 percent was added for workers with three or more dependent children, up from 40 percent in the previous year for workers with two or more children. We also estimate a model examining the impact of city-level changes to the EITC. The structure and richness of our data enable us to control for tax filer fixed effects, an important innovation from many previous EITC studies. Overall, we find that the combined EITC raises the likelihood of net-EITC income above poverty and near poverty by as much as 9 percent, with the largest consistent effects accruing to single-parent families

Optimal Capital Income Taxation with Tax Evasion

The paper discusses the applicability of optimal taxation theory to source-based capital incomes when significant tax evasion is observed. Without tax evasion a modified Ramsey Rule may reduce distortions brought by international capital mobility, leading to levying differentiated tax rates in domestic sectors inversely proportioned to observed elasticities in terms of capital mobility. The introduction of tax evasion brings additional complexity. The viability of optimal tax rates à la Ramsey is explored, and additional requirement (namely that tax evasion is either very low or very homogeneous) are shown to be necessary in order to allow policy-makers to obtain the tax rates minimizing total excess burden. Results are also provided to solve the optimal taxation objective when tax evasion is a relevant phenomenon and is not homogeneous throughout domestic sectors

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Editorial for: "3D oxygen-enhanced MR imaging at 3T MR system: comparison with thin-section CT of quantitative capability for pulmonary functional loss assessment and clinical stage classification of COPD in smokers"

No abstract available

Advances in mesothelioma imaging and implications for surgical management

In malignant pleural mesothelioma (MPM), surgery may be offered for diagnostic or palliative purposes, or in selected patients as part of a multi-modality radical treatment strategy. Imaging results are routinely used to select patients for surgery in these settings. However, the initially subtle morphology and subsequent rind-like growth pattern of the primary tumour combined with complex pleural space geometry and unfamiliar nodal drainage to present major challenges in this regard. In this article, we summarize recent imaging developments that allow clinicians to make better diagnostic, staging and perioperative decisions in MPM. We also discuss the challenges involved in selecting patients for palliative MPM surgery, particularly those with non-expansile (or trapped) lung

Concerning the feasibility of obtaining biopsies for research in relapsed ovarian cancer

No abstract available

A comparison between MRI and CT in the assessment of primary tumour volume in mesothelioma

Primary tumour staging in Malignant Pleural Mesothelioma (MPM) using Computed Tomography (CT) imaging is confounded by perception errors reflecting low spatial resolution between tumour and adjacent structures. Augmentation using perfusion CT is constrained by radiation dosage. In this study, we evaluated an alternative tumour staging method using perfusion-tuned Magnetic Resonance Imaging (MRI). Consecutive patients with suspected MPM were recruited to a prospective observational study. All had MRI (T1-weighted, isotropic, contrast-enhanced 3-Tesla perfusion imaging) and CT (contrast-enhanced) pre-biopsy. Patients diagnosed with MPM underwent MRI and CT volumetry, with readers blinded to clinical data. MRI volumetry was semi-automated, using signal intensity limits from perfusion studies to grow tumour regions within a pleural volume. A similar CT method was not possible, therefore all visible tumour was manually segmented. MRI and CT volumes were compared (agreement, correlation, analysis time, reproducibility) and associations with survival examined using Cox regression. 58 patients were recruited and had MRI before biopsy. 31/58 were diagnosed with MPM and these scans were used for volumetry. Mean (SD) MRI and CT volumes were 370 cm and 302 cm , respectively. MRI volumes were larger (average bias 61.9 cm (SD 116), 95 % limits (-165.5 - 289 cm ), moderately correlated with CT (r = 0.56, p = 0.002) and independently associated with survival (HR 4.03 (95 % CI 1.5-11.55), p = 0.006). CT volumes were not associated with survival, took longer to compute than MRI volumes (mean (SD) 151 (19) v 14 (2) minutes, p=&lt;0.0001) and were less reproducible (inter-observer ICC 0.72 for CT, 0.96 for MRI). MRI and CT generate different tumour volumes in MPM. In this study, MRI volumes were larger and were independently associated with survival. MRI volumetry was quicker and more reproducible than CT