Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD

Randomised short-term trial of high-span versus low-span APAP for treating sleep apnoea

PURPOSE: Auto-titrating continuous positive airway pressure (APAP) devices were developed to improve treatment efficacy and compliance in patients with obstructive sleep apnoea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed to compare the adherence, efficacy and tolerability of treatment with high-span versus low-span APAP. METHODS: Seventy-six newly diagnosed OSAS patients fulfilling the treatment criteria were randomised to receive high-span (HS, range 4-15cmH2O, n?=?38) or low-span (LS, range 8-12cmH2O, n?=?38) APAP. Patients were assessed at 1 and 3 months. RESULTS: Median Epworth sleepiness scale (ESS) was 13 (IQR, 6-16) and median apnoea-hypopnoea index (AHI) was 35.9 (IQR, 27.6-56.3). There were no significant differences in baseline demographic and clinical characteristics between groups. Overall, no significant differences were found at the first month assessment. After 3 months of therapy, we found again no differences in residual AHI or ESS. However, the group HS proved less adherent than group LS, respectively, with median 87 % (IQR, 60.5-97.5) versus 94 % (IQR, 80.0-98.3) of the nights using =4 h (P?=?0.014) and mean (±SD) usage 5.7?±?1.6 versus 6.4?±?1.2 h/night (P?=?0.049). The group HS reported more frequently nasal congestion, excessive oronasal dryness and nocturnal awakenings of at least moderate intensity, the latter with statistical significance (P?=?0.005). CONCLUSIONS: Both pressure ranges appear to be equally effective to correct AHI and to improve symptoms. Though, patients with high-span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.T Pinto has received financial support from Linde and Vitalaire (Healthcare Providers) for attending symposia and honoraria for speaking at symposia from Philips. After the conclusion of the study, JC Winck has started working in a global position for Linde. The remaining authors declare that they have no conflict of interest

Cloud Computing As a Tool for Enhancing Ecological Goals?

Cloud computing has been introduced as a promising information technology (IT) that embodies not only economic advantages in terms of increased efficiency but also ecological gains through saving energy. The latter has become particularly important in view of the rising energy costs of IT. The present study analyzes whether necessary preconditions for accepting cloud computing as a new infrastructure, such as awareness and perceived net value, exist on the part of the users. The analysis is based on a combined research framework of the theory of reasoned action (TRA) and the technology acceptance model (TAM) in a cloud computing setting. Two consumer surveys, the one to elicit beliefs and the second to gain insight into the ranking of the variables, are employed. This study uses structural equation modeling (SEM) to evaluate the hypotheses. The results indicate support for the proposed research framework. Surprisingly however, the ecological factor does not play a role in forming cloud computing intentions, regardless of prior knowledge or experience. Empirical evidence of this study suggests increasing efforts for informing actual and potential users, particularly in respect to possible ecological advantages through applying the new IT infrastructure

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Detection of apnoeas, hypopnoeas and arousals by the AutoSet in the sleep apnoea/hypopnoea syndrome

Limited sleep study systems are increasingly being used to diagnose the sleep apnoea/hypopnoea syndrome, but validation is essential and detection of arousal's desirable. One such system (AutoSet) was validated on an event-by-event basis, and the hypothesis that sudden large breaths detected by this system mark arousal from sleep was also examined. Twenty consecutive patients (apnoea/hypopnoea index (AHI) 39+/-6 (SEM)) underwent polysomnography (PSG), which included real-time signals of AutoSet (Version 3.03) scored events. PSG respiratory events were defined using airflow and thoracoabdominal movement and AutoSet events using nasal pressure. All apnoeas were scored by both systems, but 41% more hypopnoeas were scored on PSG and these were clinically significant, with 78% ending in cortical arousal. Twenty per cent of apnoeas and hypopnoeas scored by the AutoSet occurred during wakefulness. Large breaths, defined as a two-thirds increase in ventilation, marked 77% of respiratory-associated but only 9% of spontaneous arousals. Large breaths also marked 48% of "autonomic" arousals following respiratory events without visible electroencephalographic changes. Twenty-seven per cent of large breaths occurred during wakefulness. This study shows that the AutoSet and the standard polysomnographic approach differ in their detection of hypopnoeas. The AutoSet underdetected hypopnoeas during sleep, but also included some hypopnoeas occurring during wakefulness. Detection of large breaths may potentially be useful for identifying respiratory arousals. Detection of periods of wakefulness may improve the accuracy of the system