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One feature of papillary thyroid cancer (PTC) is the frequently present somatic BRAFV600E mutation. PTCs are also characterized by a lymphocytic infiltration, which may correlate with an improved clinical outcome. The objective of the study was the characterization of BRAFV600E specific anti-immunity in PTC patients and correlation analyses with the clinical outcome. Fourteen HLA A2 positive PTC patients were included into the study of whom tumor tissue samples were also available. Of those, 8 PTC patients revealed a somatic BRAFV600E mutation. All PTC patients were also MHC class II typed. Tetramer analyses for detection of MHC class I and MHC class II-restricted, BRAFV600E epitope-specific T cells using unstimulated and peptide-stimulated T cells were performed; correlation analyses between MHC phenotypes, T cell immunity, and the clinical course were performed. In regard to unstimulated T cells, a significantly higher amount of BRAFV600E epitope specific T cells was detected compared to a control tetramer. Importantly, after overnight peptide stimulation a significantly higher number of BRAFV600E positive and BRAF WT epitope-specific T cells could be seen. In regard to the clinical course, however, no significant differences were seen, neither in the context of the initial tumor size, nor in the context of lymph node metastases or peripheral metastastic spread. In conclusion, we clearly demonstrated a BRAF-specific tumor immunity in PTC-patients which is, however, independent of a BRAFV600E status of the PTC patients.

The potential for reducing Greenhouse gas (GHG) emissions by district renovation is largely untapped. It not only requires a thorough Energy Master Planning (EMP) of the district but also support of the decision-making processes. This can not only contribute significantly to reducing energy consumption and securing the location of energy infrastructure (generation, distribution, storage), but also to long-term sustainable development and climate neutrality. Understanding the different solutions for district renovation which include combinations with energy supply and consumption is important in districts. A technical as well as economical analysis is proposed that combines reduction of GHG emissions potential with an economic appraisal. A district near Winterthur, Switzerland was analyzed in respect to the aforementioned aspects. Site visits and structured interviews with key stakeholders were used to collect data which was then analyzed. Different renovation options were simulated, and investment and energy costs were calculated. The results show that the technical potential for a decarbonization is large. However, financial and social aspects are significant and lead to a delay in implementation.

Purpose Green building is a megatrend in corporate real estate management. This paper aims to document the prevalence of green building reporting in public firms, assess how well firms apply good practices of green building and show which firms, countries and industry sectors are particularly advanced in the application of green building technologies. Design/methodology/approach The study uses data on green building reporting, green building scores and firm characteristics of 1,281 publicly traded firms from different industries in Organisation for Economic Co-operation and Development countries over a 5-year period. Regression analysis is used to relate the adoption of green building reporting and excellence in green building to firm characteristics. Findings The results indicate that there is a huge variation in green building activities and reporting in corporate real estate management across countries and industries. The study finds that firms in the financial and health-care sectors are leading in green building reporting. Environmental, social and corporate governance-oriented, profitable and large firms receive the highest green building scores. Research limitations/implications The results in this paper rely on the reported but not inevitably monitored green building activities. There may also be companies that use green building technologies but do not report on them. The conclusions are largely based on correlations and do not allow for causal statements (endogenous variables). Practical implications The results in this paper are crucial for practitioners in corporate real estate to benchmark their green building activities and reporting. Additionally, the paper sheds light on how information on green building is propagated in the financial market. Originality/value The paper looks at the drivers and barriers of green building for 25 countries and across all industry sectors (1,281 firms). In contrast to that most of the existing literature focuses on single countries and limits the analysis to companies in the real estate and construction industry. Additionally, the paper has a joint focus on publicly available green building reporting and green building scores.

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.

This paper analyzes and contrasts the constraints, stakeholders, and framing goals that must be considered when Energy Master Planning (EMP) is conducted for communities in seven countries. The analysis is based on findings from seven countries participating in the International Energy Agency’s “Energy in Buildings and Communities Program Annex 73”. The analysis covers design constraints such as emissions, sustainability criteria, and resilience goals, regulations and directives, regional and local limitations, such as available energy types, local conditions, and various levels of stakeholders, as well as community objectives. An analysis of the various constraints on different planning levels was done, and the key stakeholders were identified. They can be characterized by different governance structures and thereby stakeholder constellations. Mapping of the stakeholders involved provides insights in further constraints resulting into issues within the EMP that will need to be addressed for multi-owner, multi-stakeholder neighborhoods and districts. With a closer look at a case study in Elverum, Norway, the paper identifies constraints related to stakeholders involved and their impact on applying EMP.

Primary aldosteronism (PA) is the most common detectable cause of secondary hypertension. The majority of patients have either an adrenal aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH) demanding different therapeutic approaches. Screening tests and imaging cannot reliably distinguish between a unilateral or bilateral PA. This review article gives an overview concerning etiology, diagnostics, and therapeutic options of PA, and reviews the indication, the technique, and relevance of selective adrenal venous sampling (AVS) in the context of the current literature and the authors' experience. AVS can verify or exclude a unilaterally dominated secretion with a high success rate. Patients with PA and a unilateral APA can be treated curatively by adrenalectomy. AVS is an established diagnostic examination for differentiation of unilateral from bilateral adrenal disease in patients with PA.· Selective adrenal venous sampling (AVS) is a safe, reliable, and minimally invasive method to detect a unilateral or bilateral adrenal adrenal gland disease.. · Verification of lateralization by AVS has direct therapeutic relevance for patients with primary aldosteronism (PA).. · AVS can be performed with low radiation exposure, without contrast medium, and with a high success rate when performed by an experienced interventional radiologist..· Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 - 666. Der primäre Hyperaldosteronismus (PHA; Conn-Syndrom) ist der häufigste nachweisbare Grund für einen sekundären arteriellen Hypertonus. Primäre Ursachen hierfür sind das Aldosteron-produzierende Adenom (APA) oder eine bilaterale adrenale Hyperplasie (BAH) mit jeweils unterschiedlicher therapeutischer Konsequenz. Weder Screening- und Funktionstests noch die Schnittbildgebung können eine unilateral dominante Hormonproduktion nachweisen. Neben einer klinischen Übersicht über Ätiologie, Diagnostik und Therapie des PHA werden in diesem Übersichtsartikel die Indikation, die Technik und der Stellenwert der selektiven Nebennierenvenenblutentnahme (NNVBE) ausführlich dargestellt und im Kontext aktueller Literatur diskutiert. Die NNVBE kann mit hoher Erfolgsrate eine unilaterale Dominanz nachweisen oder ausschließen. Patienten mit PHA und unilateralem APA können kurativ durch eine Adrenalektomie behandelt werden. Die NNVBE ist eine etablierte Intervention zur Subtypisierung des PHA in eine unilaterale oder bilaterale Erkrankung der Nebenniere.· Die Nebennierenvenenblutentnahme (NNVBE) ist eine sichere, zuverlässige und minimalinvasive Methode zur Detektion einer unilateralen oder bilateralen Erkrankung der Nebenniere.. · Der Nachweis einer Lateralisierung durch die NNVBE hat eine unmittelbare Relevanz für die kurative Therapie des primären Hyperaldosteronismus (PHA).. · Die NNVBE kann mit hoher Treffer- und Erfolgsrate ohne Kontrastmittelgabe und mit geringer Strahlenexposition in der Hand eines erfahrenen Untersuchers durchgeführt werden..· Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) – Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 – 666.

The serum sodium to urinary sodium ratio divided by the (serum potassium)2 to urinary potassium ratio (SUSPPUP formula) reflects aldosterone action. We here prospectively investigated into the usefulness of the SUSPPUP ratio as a diagnostic tool in primary hyperaldosteronism. Parallel measurements of serum and urinary sodium and potassium concentrations (given in mmol/L) in the fasting state were done in 225 patients. Of them, 69 were diagnosed with primary aldosteronism (PA), 102 with essential hypertension (EH), 26 with adrenal insufficiency (AI) and 28 did not suffer from the above-mentioned disorders and were assigned to the reference group (REF). The result of the SUSPPUP formula was highest in the PA group (7.4, 4.2&ndash, 12.3 L/mmol), followed by EH (3.2, 2.3&ndash, 4.3 L/mmol), PA after surgery (3.9, 3.0&ndash, 6.0 L/mmol), REF (3.4 &plusmn, 1.4 L/mmol) and AI (2.9 +/&minus, 1.2 L/mmol). The best sensitivity in distinguishing PA from EH was reached by multiplication of the aldosterone to renin-ratio (ARR) with the SUSPPUP formula (92.7% at a cut off &gt, 110 L/mmol), highest specificity was reached by the SUSPPUP determinations (87.2%). The integration of the SUSPPUP ratio into the ARR helps to improve the diagnosis of hyperaldosteronism substantially.

This paper analyzes and contrasts the framing goals and limitations that must be considered when energy master planning is conducted for communities in six different countries. The analyses will be based on findings from countries participating in the International Energy Agency’s “Energy in Buildings and Communities Program Annex 73”. The paper covers design constraints such as emissions, sustainability and resilience goals, regulations and directives, and regional and local limitations such as available energy types, local conditions and different levels of stakeholders as well as community objectives. We illustrate how a comprehensive consideration of these constraints can be used to guide the planner toward design options that will lead to an optimum solution for an energy master plan. An analysis of the different constraints on different planning levels was done and the key stakeholders were identified characterized by different governance structures and thereby stakeholder constellations.

Like other neo-Aristotelian ethical naturalist, Thompson holds that ethical goodness is a species of natural goodness insofar as the ethical standards to which we are subject in acting are internal to the human life-form. The distinguishing mark of Thompson’s approach consists in the claim that ethical goodness differs logically from other kinds of natural goodness: The relation between the life-form and its bearers takes a different shape in a life where the question of how to live has a place; and the concept of a form of life structured by justice introduces a further subspecification within the category of the living. The paper argues that Thompson’s insight into the essentially relational character of right and directed duty is in tension with the framework of ethical naturalism that suggests that the necessity of right can be explained in terms of what G.E.M. Anscombe calls “Aristotelian necessity” – that is, the necessity that follows from the “function” that an activity or practice serves in a lifeform.

Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3×105 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy

In the last twenty years, constitutivism has become a major contender in the field of meta-ethics and in the debate about practical rationality. But while it has attracted a lot of attention, the r...

Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin, basal CT measurement is frequently used for the preoperative diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT) cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114 patients (51 males) were included fulfilling the criteria of an increased preoperative bCT level (>10 pg/ml) and the criteria of an available postoperative histology analysis. Based on a ROC plot analysis, the cut-off values for the diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were identified. The most precise bCT thresholds for the identification of MTC were ≥46 pg/ml for males (sensitivity: 93.6%, specificity: 95.0%, PPV: 97%, NPV: 90%) and ≥35 pg/ml for females (sensitivity: 87.3%, specificity: 87.5%, PPV: 98%, NPV: 50%). Using these cut-offs, only 6% of male patients were not identified of having MTC, whereas 5% were false positive (having instead C cell hyperplasia). In females, the discrepancy was higher since 13% of female MTC patients were false negative by using the cut-off of ≥35 pg/ml, and 13% had false positive results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the identification of MTC vs. C cell hyperplasia and non-malignancy were defined, which can be used in clinical routine. In female patients, however, the accuracy is much lower compared to males.

Energy retrofitting solutions applied in residential building envelopes often consist in adding an insulation layer on the building facade and substituting the old windows with better performing ones. Such measures increase the thermal insulation of the envelope and reduce the energy need for space heating, but also reduce the daylight availability, due to the lower visible transmittance of highly insulated windows. This drawback may have strong effect in Norway, where the daylight availability in the winter season is little. This paper investigates into the consequences on energy use for space heating and electricity use for lighting given by the substitution of existing windows with highly insulated windows in Norwegian residential buildings. Three apartment buildings with different construction systems of the external facades and located in Trondheim are investigated. The buildings were built before the 1900, in the first decade of the 1900, and in the 1960s, respectively. The U-value of the external facades varies from 0.96 W/m2K to 0.26 W/m2K, and the U-value of the existing windows varies from 1.6 W/m2K to 2.8 W/m2K. The new windows have a U-value of 0.5 W/m2K. Scenarios are modelled to simulate the use patterns of artificial lighting in the apartments. Use patterns are modelled by considering occupancy hours and type of activity to cover different scenarios. Results show that the substitution of the existing windows reduces the median value of the Daylight Autonomy by at least 50%, and the additional electricity use for lighting is calculated to be between 17% and 64% of the potential energy saving for space heating.

Catecholamines stimulate renin-secretion in the juxtaglomerular cells of the kidney and a number of case reports suggest an association between pheochromocytoma and activation of the RAAS. Therefore, it could be asked whether patients suffering from pheochromocytoma with high concentrations of circulating catecholamines present with oversecretion of renin and aldosterone. We identified twelve patients with excessive catecholamine secretion due to pheochromocytoma and compared them to a group of twelve patients with essential hypertension (EH) with regard to the activation of the renin-angiotensin-aldosterone-system (RAAS). The PubMed database was screened for studies that investigate the association between pheochromocytoma and activation of the RAAS. The plasma concentrations of metanephrines (19.9-fold) and normetanephrines (29.5-fold) were significantly higher in the pheochromocytoma group than in the EH group. Renin and aldosterone levels were 1.3-fold and 1.6-fold higher, respectively, as compared to the EH group, whereas the differences were not statistically significant. There was no significant correlation between plasma metanephrine or normetanephrine levels and the plasma renin concentration (rs=0.077, rs=0.049, respectively) in our patients. The data from our institution and from review of literature suggest that an association between pheochromocytoma in the context of high plasma catecholamine levels and activation of the RAAS is present. However, results have not been consistent. Thus, other causes of RAAS-activation should be considered also in the presence of pheochromocytoma or reinvestigation for aldosteronism should be offered to such patients after removal of the catecholamine-producing tumour.

Endothelial cell-derived products influence the synthesis of aldosterone and cortisol in human adrenocortical cells by modulating proteins such as steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and CITED2. However, the potential endothelial cell-derived factors that mediate this effect are still unknown. The current study was perfomed to look into the control of β -catenin activity by endothelial cell-derived factors and to identify a mechanism by which they affect β -catenin activity in adrenocortical NCI H295R cells. Using reporter gene assays and Western blotting, we found that endothelial cell-conditioned medium (ECCM) led to nuclear translocation of β -catenin and an increase in β -catenin-dependent transcription that could be blocked by U0126, an inhibitor of the mitogen-activated protein kinase pathway. Furthermore, we found that a receptor tyrosin kinase (RTK) was involved in ECCM-induced β -catenin-dependent transcription. Through selective inhibition of RTK using Su5402, it was shown that receptors responding to basic fibroblast growth factor (bFGF) mediate the action of ECCM. Adrenocortical cells treated with bFGF showed a significant greater level of bFGF mRNA. In addition, HUVECs secrete bFGF in a density-dependent manner. In conclusion, the data suggest that endothelial cells regulate β -catenin activity in adrenocortical cells also via secretion of basic fibroblast growth factor.