Assessing site performance in the Altair study, a multinational clinical trial

Background: Reviewing clinical trial site performance identifies strategies to control outcomes. Performance across 5 geographical regions (36 sites across Asia, Australia, Europe, North America and Latin America) was investigated in a study that randomised 322 HIV-infected individuals. Methods: Regional performance was compared using descriptive analysis for time to site opening, recruitment, quality of data and laboratory samples. Follow-up consisted of 10 visits (96 weeks), electronic data collection (EDC) within 7 days of a visit and serious adverse events (SAEs) reported within 24 hours of site awareness. Results: Median days to site opening was 250 (188 to 266), ranging from 177 (158 to 200) (Australia) to 265 (205 to 270) (Europe). Median days to ethics and regulatory approval was 182 (120 to 241) and 218 (182 to 341) days, respectively. Within regions, time to approval ranged from 187 (91 to 205) days (Australia) to 276 (175 to 384) days (Europe). Time to first randomisation ranged from 282 (250 to 313) days (Australia) to 426 (420 to 433) days (North America). Conclusions: Population availability and time to ethics and regulatory approvals influence recruitment; therefore accurate feasibility assessments are critical to site selection. Time to ethics and regulatory approval may not limit site inclusion if compensated by rapid recruitment. Identifying potential delays and methods for reduction can decrease time and costs for sponsors. Trial registration: Clinical Trials.Gov identifier: NCT00335322. Date of registration: 8 June 2006

Technical note: development of a 3D printed subresolution sandwich phantom for validation of brain SPECT analysis

Purpose: To make an adaptable, head shaped radionuclide phantom to simulate molecular imaging of the brain using clinical acquisition and reconstruction protocols. This will allow the characterization and correction of scanner characteristics, and improve the accuracy of clinical image analysis, including the application of databases of normal subjects. Methods: A fused deposition modeling 3D printer was used to create a head shaped phantom made up of transaxial slabs, derived from a simulated MRI dataset. The attenuation of the printed polylactide (PLA), measured by means of the Hounsfield unit on CT scanning, was set to match that of the brain by adjusting the proportion of plastic filament and air (fill ratio). Transmission measurements were made to verify the attenuation of the printed slabs. The radionuclide distribution within the phantom was created by adding 99mTc pertechnetate to the ink cartridge of a paper printer and printing images of gray and white matter anatomy, segmented from the same MRI data. The complete subresolution sandwich phantom was assembled from alternate 3D printed slabs and radioactive paper sheets, and then imaged on a dual headed gamma camera to simulate an HMPAO SPECT scan. Results: Reconstructions of phantom scans successfully used automated ellipse fitting to apply attenuation correction. This removed the variability inherent in manual application of attenuation correction and registration inherent in existing cylindrical phantom designs. The resulting images were assessed visually and by count profiles and found to be similar to those from an existing elliptical PMMA phantom. Conclusions: The authors have demonstrated the ability to create physically realistic HMPAO SPECT simulations using a novel head-shaped 3D printed subresolution sandwich method phantom. The phantom can be used to validate all neurological SPECT imaging applications. A simple modification of the phantom design to use thinner slabs would make it suitable for use in PET

An investigation of the benefits and barriers of e-business adoption activities in Yemeni SMEs

Yemeni small‐ and medium‐sized enterprises (SMEs) are at the early stages of e‐business adoption and their owners and managers need to be supported to gain an understanding of the benefits that their business can achieve from adopting e‐business. Yemeni SMEs are at the early stages of e‐business adoption. The delay in adopting more advanced e‐business solutions are due to factors including the comparatively low level of technology usage within the organization, lack of qualified staff available to develop, implement and support firms’ websites, and limited financial resources. A lack of computer software and hardware resources appears to have a detrimental effect on e‐business adoption amongst Yemeni SMEs

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

The emergence and evolution of Neolithic cattle farming in southeastern Europe:New zooarchaeological and stable isotope data from Džuljunica-Smărdeš, in northeastern Bulgaria (ca. 6200–5500 cal. BCE)

Cattle were of great importance for the Neolithic farmers of southeastern Europe, in particular as farming expanded towards the well-watered regions of Džuljunica (ca. 6200–5500 cal. BCE), one of the earliest known Neolithic settlements in northeastern Bulgaria. The clear stratigraphy and the substantial Bos assemblage from Džuljunica Provided us with a great opportunity to investigate the beginning and evolution of cattle husbandry in the northern Balkans through stable isotope and zooarchaeological analyses. The relative abundance of Bos at Džuljunica leaves no doubt about the importance of beef and cattle herding. Mortality profiles suggest a transition in the early phases of the Neolithic from beef-oriented to mixed beef and milk production husbandry, enabled through intensified post-lactation culling. Stable carbon and oxygen isotope analysis of tooth enamel on a limited number of samples provides no evidence for an extended calving season for increasing milk availability or for vertical mobility. Stable carbon and nitrogen isotope values of bone collagen suggest that cattle were kept near the site, where C3 and C4 plants were available in summer, and that they were occasionally foddered with forest resources in the winter. Cattle experience a diachronic reduction in size on a regional scale, possibly due to farmers' choices aimed at more manageable herds consisting of smaller individuals. Restricting intermixing with local aurochs and the arrival of a new type of cattle may also have contributed to this change. Local factors or inter-regional influences may have influenced the ways cattle husbandry evolved at Džuljunica in particular and in northeastern Bulgaria more generally. More data from the region are necessary to flesh out the role of the interplay among environmental factors, local developments, and inter-regional contacts that facilitate the transfer of skills and traditions relating to the changing modes of cattle husbandry

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

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

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

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