11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher ...sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.
Abstract
The number of women employed in STEM in Australia is increasing, however, they continue to remain underrepresented in most industries. A significant corpus of literature on female ...underrepresentation has emerged in the past 20 years, however, many of those studies focus on educational access and retention and not many look at the lived experiences of women after they have left higher education. In this article, we take a different stance and explore the heterogeneous experiences of female STEM professionals in regional Australia. Through the qualitative analysis of 25 interviews, we learn what women have endured, accepted, and valued on their individual STEM journeys. While these journeys are often quite different, our interviewees independently reported having experienced similar societal prejudices and possessing similar personality traits. Our data reveals that resilience and determination proved vital for these women, as did a strong early interest in STEM. Our interviews also unearth issues in which women’s opinions are fiercely divided, such as whether positive discrimination has been a barrier or an enabler for their careers. Based on what we have learnt from their accounts, we argue that these women have ‘survived’ their work environments despite structural barriers, only due to their determination, resilience and fervent interest.
Brain positron emission tomography imaging with 18Fluorine-fluorodeoxyglucose (FDG-PET) has demonstrated utility in suspected autoimmune encephalitis. Visual and/or assisted image reading is not well ...established to evaluate hypometabolism/hypermetabolism. We retrospectively evaluated patients with autoimmune encephalitis between 2003 and 2018. Patients underwent EEG, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) sampling and autoantibodies testing. Individual FDG-PET images were evaluated by standard visual reading and assisted by voxel-based analyses, compared to a normal database. For the latter, three different methods were performed: two based on statistical surface projections (Siemens syngo.via Database Comparison, and 3D-SSP Neurostat) and one based on statistical parametric mapping (SPM12). Hypometabolic and hypermetabolic findings were grouped to identify specific patterns. We found six cases with definite diagnosis of autoimmune encephalitis. Two cases had anti-LGI1, one had anti-NMDA-R and two anti-CASPR2 antibodies, and one was seronegative. 18F-FDG-PET metabolic abnormalities were present in all cases, regardless of the method of analysis. Medial–temporal and extra-limbic hypermetabolism were more clearly depicted by voxel-based analyses. We found autoantibody-specific patterns in line with the literature. Statistical surface projection (SSP) methods (Neurostat and syngo.via Database Comparison) were more sensitive and localized larger hypermetabolic areas. As it may lead to comparable and accurate results, visual analysis of FDG-PET studies for the diagnosis of autoimmune encephalitis benefits from voxel-based analysis, beyond the approach based on MRI, CSF sample and EEG.
Background
Prior radioembolization, a simulation using
99m
Tc-macroaggregated albumin as
90
Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired ...to evaluate intrahepatic
90
Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the
90
Y activity that would get an optimal tumor response while sparing healthy tissues.
Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting
90
Y-radioembolization pre-treatment absorbed dose evaluation based on
99m
Tc-MAA images.
Methods
Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest.
Results
Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches.
DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed.
Conclusions
Significant differences among the studied dosimetry approaches for
90
Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver.
An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.
Summary
Specialized microfold (M) cells of the follicle‐associated epithelium (FAE) of the mucosal‐associated lymphoid tissue (MALT) in gut and the respiratory system play an important role in the ...genesis of both mucosal and systemic immune responses by delivering antigenic substrate to the underlying lymphoid tissue where immune responses start. Although it has been shown that dendritic cells (DC) also have the ability to sample antigens directly from the gut lumen, M cells certainly remain the most important antigen‐sampling cell to be investigated in order to devise novel methods to improve mucosal delivery of biologically active compounds. Recently, novel information on the interactions between bacteria and FAE have come to light that unveil further the complex cross‐talk taking place at mucosal interfaces between bacteria, epithelial cells and the immune system and which are central to the formation and function of M cells. In particular, it has been shown that M cell mediated transport of antigen across the FAE is improved rapidly by exposure to certain bacteria, thus opening the way to identify new means to achieve a more effective mucosal delivery. Here, these novel findings and their potential in mucosal immunity are analysed and discussed, and new approaches to improve antigen delivery to the mucosal immune system are also proposed.
Anaplastic large cell lymphoma (ALCL) with leukaemic presentation (either ab initio or along the course of the disease) has been rarely reported. Irrespective of ALK expression in the neoplastic ...cells, it features a dismal prognosis. We report a rare case of leukaemic, small cell variant ALK-positive ALCL with 9-year survival in a young woman who was treated upfront with corticosteroids and standard chemotherapy, and review thoroughly the previously published cases. Such an unexpected, good outcome hints at the existence of different clinical subgroups in the leukaemic variant of ALK-positive ALCL.
Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an ...increasingly recognized role in tumour biology. The aim of this study was to explore the role of DUSP6 expression in the prognosis of human non-small cell lung cancer (NSCLC). DUSP6 expression levels were evaluated by real-time quantitative reverse transcription polymerase chain reaction (PCR) in 60 NSCLC samples from patients who underwent pulmonary resection at 12 de Octubre University Hospital. We performed a statistical analysis to investigate the correlation of DUSP6 expression and the clinical outcomes. We found that 66.7 % of the tumour samples show the downregulation of DUSP6 at the messenger RNA (mRNA) levels compared to benign epithelial lung tissues and 55 % of them show at least twofold downregulation of DUSP6 gene expression. Patients were classified into three groups according to their DUSP6 expression levels and those with very low levels (at least twofold downregulation) had the worst outcomes. Using the value of twice below the mean value in benign epithelial lung tissue as a cutoff, the overall survival of patients with very low DUSP6 levels was significantly lower than that in the rest of patients (31.9 ± 18.8 months vs. not reached,
P
= 0.049). This was most pronounced in adenocarcinoma histology and high-stage tumour samples. Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC.
Online learning is increasingly ubiquitous in higher education. However, research regarding online teaching often focuses on the affordances of the online environment rather than on the quality of ...pedagogy. In this paper we consider how online learning could be enhanced using rich pedagogical models that are consistent with a wealth of existing knowledge on pedagogy for face-to-face settings. To do so, we apply an established framework, the Quality Teaching model, to explore pedagogy in the online environment and illustrate its potential benefits using a case study of 60 students in a tertiary mathematics teacher education program. We conclude that the use of an evidence-based pedagogical model can help guide online instructors in the development of high quality online courses. Author abstract
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