Parliamentary scrutiny of EU law proposals in Denmark: why do governments request a negotiation mandate?

"Political scientists have been concerned about the loss of power of national parliaments through the shift of competences to the EU level. In this respect the Danish system of parliamentary scrutiny has been recommended as being highly effective. In this paper, we explain why the Folketing issues negotiation mandates on some EU law proposals whereas the government can freely chose its negotiation position on other proposals. Our empirical analysis of Danish scrutiny decision between 2006 and 2008 uncovers three answers. First, in contrast to other scrutiny measures, most of which can be initiated by single party groups, the issuance of negotiation mandates is a collective decision. Specifically, it requires the consent of a majority of deputies in the Folketing. As a consequence, the position of the minority government must win the support of a third party. This third party tends to requests a negotiation mandate if it fears that collusion between the government and its international partners might violate its interests. Second, the leading minister requests a negotiation mandate if a majority of Danish parties stand united against an adverse majority in the Council. Third, the coalition partner requests a negotiation mandate to control the leading minister in case of significant intra coalition dissent." [author's abstract

Evidence-based cross validation for acoustic power transmission for a novel treatment system

Introduction: The novel Trans-Fusimo Treatment System (TTS) is designed to control Magnetic Resonance guided Focused Ultrasound (MRgFUS) therapy to ablate liver tumours under respiratory motion. It is crucial to deliver the acoustic power within tolerance limits for effective liver tumour treatment via MRgFUS. Before application in a clinical setting, evidence of reproducibility and reliability is a must for safe practice. Materials and methods: The TTS software delivers the acoustic power via ExAblate-2100 Conformal Bone System (CBS) transducer. A built-in quality assurance application was developed to measure the force values, using a novel protocol to measure the efficiency for the electrical power values of 100 and 150W for 6s of sonication. This procedure was repeated 30 times by two independent users against the clinically approved ExAblate-2100 CBS for cross-validation. Results: Both systems proved to deliver the power within the accepted efficiency levels (70–90%). Two sample t-tests were used to assess the differences in force values between the ExAblate-2100 CBS and the TTS (p > 0.05). Bland-Altman plots were used to demonstrate the limits of agreement between the two systems falling within the 10% limits of agreement. Two sample t-tests indicated that TTS does not have user dependency (p > 0.05). Conclusions: The TTS software proved to deliver the acoustic power without exceeding the safety levels. Results provide evidence as a part of ISO13485 regulations for CE marking purposes. The developed methodology could be utilised as a part of quality assurance system in clinical settings; when the TTS is used in clinical practice

Altered Inactivation of Ca2+ Current and Ca2+ Release in Mouse Muscle Fibers Deficient in the DHP receptor γ1 subunit

Functional impacts of the skeletal muscle-specific Ca2+ channel subunit γ1 have previously been studied using coexpression with the cardiac α1C polypeptide in nonmuscle cells and primary-cultured myotubes of γ1-deficient mice. Data from single adult muscle fibers of γ−/− mice are not yet available. In the present study, we performed voltage clamp experiments on enzymatically isolated mature muscle fibers of the m. interosseus obtained from γ+/+ and γ−/− mice. We measured L-type Ca2+ inward currents and intracellular Ca2+ transients during 100-ms step depolarizations from a holding potential of −80 mV. Ratiometric Ca2+ transients were analyzed with a removal model fit approach to calculate the flux of Ca2+ from the sarcoplasmic reticulum. Ca2+ current density, Ca2+ release flux, and the voltage dependence of activation of both Ca2+ current and Ca2+ release were not significantly different. By varying the holding potential and recording Ca2+ current and Ca2+ release flux induced by 100-ms test depolarizations to +20 mV, we studied quasi-steady-state properties of slow voltage–dependent inactivation. For the Ca2+ current, these experiments showed a right-shifted voltage dependence of inactivation. Importantly, we could demonstrate that a very similar shift occurred also in the inactivation curve of Ca2+ release. Voltages of half maximal inactivation were altered by 16 (current) and 14 mV (release), respectively. Muscle fiber bundles, activated by elevated potassium concentration (120 mM), developed about threefold larger contracture force in γ−/− compared with γ+/+. This difference was independent of the presence of extracellular Ca2+ and likely results from the lower sensitivity to voltage-dependent inactivation of Ca2+ release. These results demonstrate a specific alteration of voltage-dependent inactivation of both Ca2+ entry and Ca2+ release by the γ1 subunit of the dihydropyridine receptor in mature muscle fibers of the mouse

Methodology on Quantification of Sonication Duration for Safe Application of MR Guided Focused Ultrasound for Liver Tumour Ablation

Background and objective Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for liver tumour ablation is a challenging task due to motion caused by breathing and occlusion due the ribcage between the transducer and the tumour. To overcome these challenges, a novel system for liver tumour ablation during free breathing has been designed. Methods The novel TRANS-FUSIMO Treatment System (TTS, EUFP7) interacts with a Magnetic Resonance (MR) scanner and a focused ultrasound transducer to sonicate to a moving target in liver. To meet the requirements of ISO 13485; a quality management system for medical device design, the system needs to be tested for certain process parameters. The duration of sonication and, the delay after the sonication button is activated, are among the parameters that need to be quantified for efficient and safe ablation of tumour tissue. A novel methodology is developed to quantify these process parameters. A computerised scope is programmed in LabVIEW to collect data via hydrophone; where the coordinates of fiber-optic sensor assembly was fed into the TRANS-FUSIMO treatment software via Magnetic Resonance Imaging (MRI) to sonicate to the tip of the sensor, which is synchronised with the clock of the scope, embedded in a degassed water tank via sensor assembly holder. The sonications were executed for 50 W, 100 W, 150 W for 10 s to quantify the actual sonication duration and the delay after the emergency stop by two independent operators for thirty times. The deviation of the system from the predefined specs was calculated. Student's-T test was used to investigate the user dependency. Results The duration of sonication and the delay after the sonication were quantified successfully with the developed method. TTS can sonicate with a maximum deviation of 0.16 s (Std 0.32) from the planned duration and with a delay of 14 ms (Std 0.14) for the emergency stop. Student's T tests indicate that the results do not depend on operators (p > .05). Conclusion The evidence obtained via this protocol is crucial for translation- of-research into the clinics for safe application of MRgFUS. The developed protocol could be used for system maintenance in compliance with quality systems in clinics for daily quality assurance routines

Ideas for data management and data handling concept for COMPACT

The future complex plasma facility COMPACT will allow the investigation of large three-dimensional complex plasmas under microgravity conditions aboard the International Space Station (ISS). COMPACT is a project with international scientific contributions, supported by space agencies (DLR, NASA, ESA) and NSF. Data generated by experiments on the ISS have a considerable value considering the effort needed to repeat an experiment. To maximize the use of the unique data in the scientific community, data management and data handling must be designed sensibly. We have learned from previous projects that it makes sense to deal with this at an early stage. Ultimately, the data must be handled on many levels. We will present ideas for reliable data handling concepts. This should all together form a chain of trust starting in the early stage (during the experiment) and goes on even after paper and data publication. Following as early as possible the FAIR principles creates confidence in the scientific results. Further, concepts based on tools like RIAF and deploy2zenodo are presented. This work is funded by DLR/BMWi (FKZ 50WM2161)

Evaluation of a developed MRI-guided focused ultrasound system in 7 T small animal MRI and proof-of-concept in a prostate cancer xenograft model to improve radiation therapy

Focused ultrasound (FUS) can be used to physiologically change or destroy tissue in a non-invasive way. A few commercial systems have clinical approval for the thermal ablation of solid tumors for the treatment of neurological diseases and palliative pain management of bone metastases. However, the thermal effects of FUS are known to lead to various biological effects, such as inhibition of repair of DNA damage, reduction in tumor hypoxia, and induction of apoptosis. Here, we studied radiosensitization as a combination therapy of FUS and RT in a xenograft mouse model using newly developed MRI-compatible FUS equipment. Xenograft tumor-bearing mice were produced by subcutaneous injection of the human prostate cancer cell line PC-3. Animals were treated with FUS in 7 T MRI at 4.8 W/cm2 to reach ~45 °C and held for 30 min. The temperature was controlled via fiber optics and proton resonance frequency shift (PRF) MR thermometry in parallel. In the combination group, animals were treated with FUS followed by X-ray at a single dose of 10 Gy. The effects of FUS and RT were assessed via hematoxylin-eosin (H&E) staining. Tumor proliferation was detected by the immunohistochemistry of Ki67 and apoptosis was measured by a TUNEL assay. At 40 days follow-up, the impact of RT on cancer cells was significantly improved by FUS as demonstrated by a reduction in cell nucleoli from 189 to 237 compared to RT alone. Inhibition of tumor growth by 4.6 times was observed in vivo in the FUS + RT group (85.3%) in contrast to the tumor volume of 393% in the untreated control. Our results demonstrated the feasibility of combined MRI-guided FUS and RT for the treatment of prostate cancer in a xenograft mouse model and may provide a chance for less invasive cancer therapy through radiosensitization

Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth-cohort

An individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N=869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC=.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood

Toxoplasma and Plasmodium protein kinases: roles in invasion and host cell remodelling

Some apicomplexan parasites have evolved distinct protein kinase families to modulate host cell structure and function. Toxoplasma gondii rhoptry protein kinases and pseudokinases are involved in virulence and modulation of host cell signalling. The proteome of Plasmodium falciparum contains a family of putative kinases called FIKKs, some of which are exported to the host red blood cell and might play a role in erythrocyte remodelling. In this review we will discuss kinases known to be critical for host cell invasion, intracellular growth and egress, focusing on (i) calcium-dependent protein kinases and (ii) the secreted kinases that are unique to Toxoplasma (rhoptry protein kinases and pseudokinases) and Plasmodium (FIKKs)