A comparative study of NaI(Tl), CeBr3, and CZT for use in a real-time simultaneous nuclear and fluoroscopic dual-layer detector

Simultaneous acquisition of nuclear and fluoroscopic projections could be of benefit for image-guided radionuclide administration. A gamma camera positioned behind an x-ray flat panel detector can accomplish such simultaneous acquisition, but the gamma camera performance suffers from the intense x-ray dose. A regular NaI(Tl)-based camera has nominal performance up to 0.02 nGy dose per pulse, whereas 10 nGy dose is expected for our foreseen applications. We evaluated the performance of CeBr3- and CZT-based detectors and investigated a cost-effective improvement of a regular NaI(Tl)-based camera by the introduction of a high-pass filter and shorting circuit. A CeBr3-based detector was exposed to 5 mGy x-ray dose and the resulting light emission was measured over time to quantify the crystal afterglow, allowing comparison with a previously measured NaI(Tl)-based detector. The NaI(Tl)-, CeBr3- and CZT-based detectors were exposed to x-ray pulse sequences with dose from 0.06 to 60 nGy, while being irradiated with a gamma source. The mean gamma energy and energy resolution in between the x-ray pulses were measured as a reference of the detector performance. The afterglow signal after 3 ms was 14.1% for the NaI(Tl)-based detector, whereas for the CeBr3-based detector it was only 0.1%. The limits for a proper functioning detectors are 0.32 nGy for the NaI(Tl)-based detector with high-pass filter and shorting circuit and 18.94 nGy for the one with CeBr3. No energy degradation was observed for the CZT module in the studied dose range. The performance of regular NaI(Tl)-based gamma cameras deteriorates when exposed to high x-ray doses. CeBr3 and CZT are much better suited for introduction into a dual-layer detector but have high associated costs. Addition of a high-pass filter and shorting circuit into the PMT of a NaI(Tl)-based detector is a cost-effective solution that works well for low dose levels

A comparative study of NaI(Tl), CeBr3, and CZT for use in a real-time simultaneous nuclear and fluoroscopic dual-layer detector

Simultaneous acquisition of nuclear and fluoroscopic projections could be of benefit for image-guided radionuclide administration. A gamma camera positioned behind an x-ray flat panel detector can accomplish such simultaneous acquisition, but the gamma camera performance suffers from the intense x-ray dose. A regular NaI(Tl)-based camera has nominal performance up to 0.02 nGy dose per pulse, whereas 10 nGy dose is expected for our foreseen applications. We evaluated the performance of CeBr3- and CZT-based detectors and investigated a cost-effective improvement of a regular NaI(Tl)-based camera by the introduction of a high-pass filter and shorting circuit. A CeBr3-based detector was exposed to 5 mGy x-ray dose and the resulting light emission was measured over time to quantify the crystal afterglow, allowing comparison with a previously measured NaI(Tl)-based detector. The NaI(Tl)-, CeBr3- and CZT-based detectors were exposed to x-ray pulse sequences with dose from 0.06 to 60 nGy, while being irradiated with a gamma source. The mean gamma energy and energy resolution in between the x-ray pulses were measured as a reference of the detector performance. The afterglow signal after 3 ms was 14.1% for the NaI(Tl)-based detector, whereas for the CeBr3-based detector it was only 0.1%. The limits for a proper functioning detectors are 0.32 nGy for the NaI(Tl)-based detector with high-pass filter and shorting circuit and 18.94 nGy for the one with CeBr3. No energy degradation was observed for the CZT module in the studied dose range. The performance of regular NaI(Tl)-based gamma cameras deteriorates when exposed to high x-ray doses. CeBr3 and CZT are much better suited for introduction into a dual-layer detector but have high associated costs. Addition of a high-pass filter and shorting circuit into the PMT of a NaI(Tl)-based detector is a cost-effective solution that works well for low dose levels

Melanocortin 2 Receptor-Associated Protein (MRAP) and MRAP2 in Human Adrenocortical Tissues: Regulation of Expression and Association with ACTH Responsiveness

Context: ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling are dependent on the MC2R accessory protein (MRAP). The MRAP homolog MRAP2 also transports the MC2R to the cell surface but might prevent activation. Objective: The objective of the investigation was to study the regulatory pathways of MRAP and MRAP2 and their contributions to ACTH responsiveness in human adrenal tissues. Design and Setting: MRAP, MRAP2, and MC2R expression levels were studied in 32 human adrenocortical samples. Regulation of these mRNAs was investigated in 43 primary adrenal cultures, stimulated with ACTH, forskolin, angiotensin II (AngII), phorbol-12-myristate-13-acetate (PMA), or dexamethasone. The induction of cortisol, cAMP, and ACTH-responsive genes after treatment with ACTH was related to MRAP, MRAP2, and MC2R expression levels. Results: MRAP and MRAP2 levels were lower in adrenocortical carcinomas (ACC) than in other adrenal tissues (P < 0.001). Patient ACTH and cortisol levels were associated with adrenal levels of MRAP and MC2R in adrenal hyperplasia samples (P < 0.05) but not in tumors. ACTH induced the expression of MRAP 11 +/- 2.1-fold and MC2R 20 +/- 3.8-fold in all adrenal tissue types (mean +/- SEM, both P < 0.0001), whereas AngII augmented these mRNAs 4.0 +/- 1.2-fold and 12.6 +/- 3.2-fold (P < 0.0001) in all Conclusion: MRAP and MC2R expression is induced by ACTH and AngII, which would facilitate cell surface receptor availability. Physiological expression levels of MRAP, MRAP2, and MC2R were not limiting for ACTH sensitivity. (J Clin Endocrinol Metab 97: E747-E754, 2012

ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11 beta-hydroxylase

<p>Background: Adrenal Cushing's syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro.</p><p>Methods: In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-) clinical hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were determined in the adrenal tissues.</p><p>Results: Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. AVP and metoclopramide were the most prevalent hormonal stimuli triggering positive responses in vivo. Catecholamines induced short-term cortisol production more often in AIMAH cultures compared to other adrenal cells. Short-and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP also increased steroidogenic enzyme mRNA expression, among which an aberrant induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced stimulation of CYP11B1.</p><p>Conclusions: Multiple hormonal signals can simultaneously induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and expression of its type 1a receptor was aberrantly linked to CYP11B1 expression.</p>

Online political debate, unbounded citizenship, and the problematic nature of a transnational public sphere

Citizenship has always been a dynamic notion, subject to change and permanent struggle over its precise content and meaning. Recent technological, economic, and political transformations have led to the development of alternative notions of citizenship that go beyond the classic understanding of its relationship to nation states and rights. Civil society actors play an important role in this process by organizing themselves at a transnational level, engaging with issues that transcend the boundaries of the nation state and questioning the democratic legitimacy of other transnational actors such as international and corporate organizations. They also allow citizens to engage with "unbounded" issues and to construct a transnational public sphere where such issues can be debated. It is often assumed that the Internet plays a crucial role in enabling this transnational public sphere to take shape. Empirical analysis of discussion forums and mailing lists developed by transnational civil society actors shows, however, that the construction of such a transnational public sphere is paved with constraints. To speak of a unified transnational public sphere is therefore deemed to be problematic. It cannot be seen or construed without taking into account the local, the national, and enforceable rights in order to materialize the ideas and hopes being voiced through civil society

DNA analysis of <i>INHA</i> in 37 human adrenocortical carcinomas.

†<p>expressed in years.</p>‡<p>all detected rare variants were heterozygous.</p>¶<p>this SNP was only studied in frozen tissue samples.</p

The human inhibin α-subunit (<i>INHA</i>) gene.

<p>Located at 2q35, <i>INHA</i> is composed of two exons separated by a 2 kb intron. The coding sequence is composed of 1101 bps. The regions sequenced in this study are indicated by the continuous arrows. The areas investigated for methylation are depicted by the dashed arrows; CpG dinucleotides successfully characterized are shown as open circles.</p

<i>INHA</i> methylation analysis in adrenocortical tissues.

<p>Quantitative methylation analysis of four CpG dinucleotides in the <i>INHA</i> promoter was performed in 3 normal adrenals and 19 ACCs. Individual CpGs are indicated on the x-axis by the bp number located 5′ from the ATG start site. 0 indicates no methylation of DNA whereas 1 indicates that all DNA tested in the tissue sample is methylated. Individual data points are composed of a mean of triplicate measurements.</p

<i>INHA</i> mRNA analysis in adrenocortical tissues.

<p>(A) Quantitative <i>INHA</i> mRNA analysis was comparable in normal adrenals (Nl, n = 10), adrenocortical hyperplasia (Hyp, n = 20), adenomas (ADA, n = 11) and carcinomas (ACC, n = 25). The ACC sample harbouring the S184F variantis displayed as an open circle. Bar represents mean. (B) Variation in rs11893842 (−124A>G) was associated with changes in <i>INHA</i> gene expression. Bars represent means, *P<0.05. (C) Negative association between promoter methylation of the <i>INHA</i> gene and <i>INHA</i> mRNA expression (r = −0.701, P = 0.0036). (D) Lack of correlation between <i>INHA</i> mRNA expression and serum inhibin pro-αC Z-scores in ACC patients (r = −0.473, p = 0.10).</p