Oncoscience (Germany)

There is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biologic mechanisms underlying these differences remain unknown. This study determines the feasibility of using diffusion MRI to characterize and define the potential spatiotemporal microstructural differences in the brain following psilocybin treatment in C57BL/6J male mice. Eleven- to 15-week-old C57BL/6J male mice were randomly assigned to receive psilocybin, 6-fluoro-N, N-diethyltryptamine, or saline and ex vivo imaged 24 hours (n=18) and 72 hours (n=18) posttreatment. A 1-way ANOVA with multiple comparison testing (Bonferroni correction) assessed diffusion metric differences (tractography, DTI, neurite orientation dispersion and density imaging) between the 3 groups and was performed in the following regions of interest: amygdala, striatum, hippocampus, thalamus, primary visual cortex area, frontal association cortex, and medial prefrontal cortex at 24 hours and 72 hours postdrug administration. Psilocybin-treated mice demonstrated structural connectivity differences at 72 hours in the frontal association cortex (compared with saline, mean tract length increases, P = .03). Psilocybin also induced microstructural differences at 24 hours postinjection in the primary visual cortex (compared with saline, mean diffusivity [MD] increases, P = .02) and 72 hours postinjection in the striatum (compared with saline; MD increases, P = .02, neurite density index [NDI] decreases, P = .02) and hippocampus (compared with saline; MD increases, P = .04, NDI decreases, P = .02). Diffusion microstructure imaging and white matter tractography are sensitive methods to detect and characterize the neural substrates and microstructural differences accompanying psilocybin treatment. These findings suggest the potential role for diffusion microstructure imaging to quantify the bioeffects of psychedelics like psilocybin on the brain, monitor treatment response, and identify salient clinical end points in an emerging therapeutic option for patients with MDD.

This paper proposes a digital cascaded control strategy for integrating an LLC resonant converter into a DC Microgrid. The designed control scheme is particularly suitable for battery storage applications in discharging mode. The outer loop of the cascaded controller is a droop controller which provides the reference current according to the DC grid voltage. The inner loop regulates the current according to the reference by pulse frequency modulation (PFM). A seventh-order state-space model based on first harmonic approximation (FHA) and extended describing function (EDF) was built to assist the controller design. The proposed control scheme is validated for both buck and boost operation mode in the PLECS simulation environment.

This pilot study aimed to evaluate a continuous glucose monitoring (CGM) based approach to study the effects of a functional drink containing specific amino acids and chromium picolinate (FD) and a combination of FD with a juice (FDJ) on postprandial glucose in a close to real life setting. The predefined primary endpoint for this study was the 120-min incremental area under the glucose curve (iAUC0−120min) after meals. It was estimated that using CGM and repeated meals in 6 participants could be sufficient to match the power of the previous study in regards to the quantity of meals. Participants followed a pre-specified meal schedule over 9 days and consumed the drinks three times daily with main meals. Differences between drinks were analyzed by analysis of covariances (ANCOVA) with subject number and activity as random factors and nutrient composition as covariates. In 156 meals available for analysis, a significant 34% reduction of glucose iAUC0−120min was shown for FDJ (p < 0.001). FD did not show a significant effect on its own, but a significant reduction of 17.6% (p = 0.007) was shown in pooled data for FD and FDJ. While the differences between the two functional drinks used were not the primary focus of this study, it was sufficiently powered to detect previously described effects in 60 participants in a cross-over design under laboratory settings. The design presented defines a novel and cost-effective approach using CGM devices and app-based lifestyle tracking for studying nutritional effects on glucose at home in a close to real-life setting.

Oxygen plays a fundamental role in cellular energy metabolism, differentiation and cell biology in general. Consequently, in vitro oxygen sensing can be used to assess cell vitality and detect specific mechanisms of toxicity. In 2D in vitro models currently used, the oxygen supply provided by diffusion is generally too low, especially for cells having a high oxygen demand. In organ-on-chip systems, a more physiologic oxygen supply can be generated by establishing unidirectional perfusion. We established oxygen sensors in an easy-to-use and parallelized organ-on-chip system. We demonstrated the applicability of this system by analyzing the influence of fructose (40 mM, 80 mM), ammonium chloride (100 mM) and Na-diclofenac (50 µM, 150 µM, 450 µM, 1500 µM) on primary human hepatocytes (PHH). Fructose treatment for two hours showed an immediate drop of oxygen consumption (OC) with subsequent increase to nearly initial levels. Treatment with 80 mM glucose, 20 mM lactate or 20 mM glycerol did not result in any changes in OC which demonstrates a specific effect of fructose. Application of ammonium chloride for two hours did not show any immediate effects on OC, but qualitatively changed the cellular response to FCCP treatment. Na-diclofenac treatment for 24 hours led to a decrease of the maximal respiration and reserve capacity. We also demonstrated the stability of our system by repeatedly treating cells with 40 mM fructose, which led to similar cell responses on the same day as well as on subsequent days. In conclusion, our system enables in depth analysis of cellular respiration after substrate treatment in an unidirectional perfused organ-on-chip system.

High postprandial blood glucose levels are associated with increased mortality, cardiovascular events and development of diabetes in the general population. Interventions targeting postprandial glucose have been shown to prevent both cardiovascular events and diabetes. This study evaluates the efficacy and safety of a novel nutritional supplement targeting postprandial glucose excursions in non-diabetic adults. Sixty overweight healthy male and female participants were recruited at two centers and randomized in a double-blind, placebo-controlled, crossover design. The supplement, a water-based drink containing 2.6g of amino acids (L-Leucine, L-Threonine, L-Lysine Monohydrochloride, L-Isoleucine, L-Valine) and 250 mcg of chromium picolinate, was consumed with a standardized carbohydrate-rich meal. The primary endpoint was the incremental area under the curve (iAUC) for venous blood glucose from 0 to 120 minutes. Secondary endpoints included glucose iAUC 0-180 minutes and the maximum glucose concentration (Cmax), for both venous and capillary blood glucose. In the intention-to-treat-analysis (n = 60) the supplement resulted in a decreased venous blood glucose iAUC0-120min compared to placebo, mean (SE) of 68.7 (6.6) versus 52.2 (6.8) respectively, a difference of -16.5 mmol/L•min (95% CI -3.1 to -30.0, p = 0.017). The Cmax for venous blood glucose for the supplement and placebo were 6.45 (0.12) versus 6.10 (<0.12), respectively, a difference of -0.35 mmol/L (95% CI -0.17 to -0.53, p<0.001). In the per protocol-analysis (n = 48), the supplement resulted in a decreased Cmax compared to placebo from 6.42 (0.14) to 6.12 (0.14), a difference of -0.29 mmol/L (95% CI -0.12 to -0.47, p = 0.002). No significant differences in capillary blood glucose were found, as measured by regular bed-side glucometers. The nutritional supplement drink containing amino acids and chromium improves the postprandial glucose homeostasis in overweight adults without diabetes. Future studies should clarify, whether regular consumption of the supplement improves markers of disease or could play a role in a diet aiming at preventing the development of diabetes.

© 2019 - IOS Press and the authors. When producing anonymised microdata for research, national statistics institutes (NSIs) identify a number of 'risk scenarios' of how intruders might seek to attack a confidential dataset. This approach has been criticised for focusing on data protection only without sufficient reference to other aspects of confidentiality management, and for emphasising theoretical possibilities rather than evidence-based attacks. An alternative 'user-centred' approach offers more efficient outcomes and is more in tune with the spirit of data protection legislation, as well as the letter. The user-centred approach has been successfully adopted in controlled research facilities. However, it has not been systematically applied beyond these specialist facilities. This paper shows how the same approach can be applied to distributed data with limited NSI control. It describes the creation of a scientific use file (SUF) for business microdata, traditionally hard to protect. This case study demonstrates that an alternative perspective can have dramatically different outcomes as compared with established anonymization strategies; in the case study discussed, the alternative approach reduces 100% perturbation of continuous variables to under 1%. The paper also considers the implications for future developments in official statistics, such as administrative data and 'big data'.

A small, self-selected discussion group was convened to consider issues surrounding impact factors at the first meeting of the Open Scholarship Initiative in Fairfax, Virginia, USA, in April 2016, and focused on the uses and misuses of the Journal Impact Factor (JIF), with a particular focus on research assessment. The group’s report notes that the widespread use, or perceived use, of the JIF in research assessment processes lends the metric a degree of influence that is not justified on the basis of its validity for those purposes, and retards moves to open scholarship in a number of ways. The report concludes that indicators, including those based on citation counts, can be combined with peer review to inform research assessment, but that the JIF is not one of those indicators. It also concludes that there is already sufficient information about the shortcomings of the JIF, and that instead actions should be pursued to build broad momentum away from its use in research assessment. These actions include practical support for the San Francisco Declaration on Research Assessment (DORA) by research funders, higher education institutions, national academies, publishers and learned societies. They also include the creation of an international “metrics lab” to explore the potential of new indicators, and the wide sharing of information on this topic among stakeholders. Finally, the report acknowledges that the JIF may continue to be used as one indicator of the quality of journals, and makes recommendations how this should be improved.OSI2016 Workshop Question: Impact FactorsTracking the metrics of a more open publishing world will be key to selling “open” and encouraging broader adoption of open solutions. Will more openness mean lower impact, though (for whatever reason—less visibility, less readability, less press, etc.)? Why or why not? Perhaps more fundamentally, how useful are impact factors anyway? What are they really tracking, and what do they mean? What are the pros and cons of our current reliance on these measures? Would faculty be satisfied with an alternative system as long as it is recognized as reflecting meaningfully on the quality of their scholarship? What might such an alternative system look like?

La prise de risque constitue une demarche ethique articulee a la complexite de la pratique actuelle du travail social. En proposant un questionnement de l’equipe professionnelle, elle s’inscrit dans une demarche coherente du projet de prise en charge de l’usager. Cet agir institutionnel passe par un decryptage de la pratique et s’articule a l’experience quotidienne. Le lien entre la prise de risque et la pratique du travail social donne du sens au metier et permet la rencontre dans la subjectivite.

2033 Background: The receptor for epidermal growth factor (EGF-R) has consistently been found expressed or overexpressed in human malignant glioma disease. Therapeutic targeting of the EGF-R has shown mixed responses which appear to be restricted by specific features of the tumor cells.Nimotuzumab binds preferentially to highly over expressing cells, a phase III trial was initiated to test efficacy in glioma. Methods: Nimotuzumab was tested in an open label, randomized, multicenter Phase III trial in patients with histologically confirmed, newly diagnosed glioblastoma. 12 consecutive weekly infusions of 400mg during standard radiotherapy with Temozolomide followed by biweekly infusions of 400mg arm A was randomized against standard radio chemotherapy alone arm B. Primary endpoint was PFS as determined by centralized neuro-imaging review. OS as secondary endpoint with quality of life, safety as additional parameters.MGMT and EGF-R were assessed where sufficient materials could be retrieved as well as tumor hypoxia. Results: Between 2007 and 2010, 149 patients were randomized and 142 were available for analysis. Stratification according to resection status resulted in 40 pts in the treatment arm and 41 in the control arm with residual tumor and 31 vs 30 pts without residual tumor. PFS: 12 month was 25.5% arm A vs 20.3% in arm B (p = 0.78) and OS: 679 days vs 596 days. For non - methylated MGMT the difference was most notable: OS arm A 28 pats: 19.6 months vs arm B 28 pats 15.0 months EGF-R amplification, gave no clear signal, neither was there a statistically significant treatment effect between with or without residual tumor. Tumor hypoxia does not appear to have predictive value in the overall group but possibly in subgroups.AEs and SAEs did not reveal a new specific toxicity profile beyond the known side effects from glioma treatment with current standard. Conclusions: Nimotuzumab shows a clear trend towards efficacy in MGMT non-methylated glioblastoma patients. Safety profile and indications for subgroup efficacy potentially justify focused evaluation of antibody therapy against glioblastoma.