A risk-consistent approach is proposed for the evaluation of behaviour factors that are compatible with Eurocode 8, using nonlinear static and dynamic analysis. It comprises seven discrete steps, involving hazard assessment and record selection at multiple sites, designing and modelling multiple archetype buildings and assessing their performance vis-à-vis target safety objectives. In all cases, uncertainty is incorporated and propagated to the final results whereby a flexible verification procedure is offered to account for the confidence of the investigator on the data available. An example application is offered on steel concentrically braced frames, highlighting the need for selecting appropriate performance targets for Europe. The overall added value goes beyond the current state of art, offering a consistent risk basis for the seismic design of different systems that is compatible with current uniform hazard design spectra and can benefit from future risk-targeted hazard maps.
The disposition of the synthetic corticosteroids, dexamethasone and prednisolone, in CSF was evaluated following bolus intravenous (IV) and intrathecal (IT) injection in a nonhuman primate model. Steroid concentration in plasma and CSF was measured with a radioimmunoassay following celite column chromatography. The CSF to plasma ratios of dexamethasone and prednisolone following IV bolus administration were 0.15 +/- 0.02 and 0.08 +/- 0.03, respectively. Although peak levels of the two steroids in the CSF reached equally potent levels when administered systemically in equipotent doses, the half-life of prednisolone in the CSF was shorter. In addition, there was a significant difference in the plasma protein binding of the two steroids, which may account for the differences in their CSF pharmacokinetics. Dexamethasone was 70% protein bound over a wide concentration range, while the protein binding of prednisolone was concentration dependent, ranging from 60% at 10 mumol/L to 95% at 0.5 mumol/L and below. After the initial distribution phase in plasma, CSF concentrations of dexamethasone and prednisolone approximated free plasma concentrations, indicating that penetration into the CSF was limited primarily by protein binding. At the plasma concentrations achieved following oral administration of standard doses of prednisone in children, the prednisolone (the active metabolite) is greater than 90% protein bound. The proportionally higher free plasma levels of dexamethasone result in greater penetration into the CSF. These findings may explain the lower rates of meningeal leukemia observed in children receiving dexamethasone instead of prednisone for the treatment of acute lymphoblastic leukemia (ALL).
This study presents the effect of Greek fly ash as a partial replacement of cement, on the durability and mechanical resistance of reinforced concrete immersed in sodium chloride (NaCl) solution. The aforementioned additive was used at 5% w.w and 10% w.w cement replacement. The compressive strength and static elastic modulus of the laboratory produced concrete specimens were measured after partial immersion in 3.5% w.w NaCl solution. Furthermore, the anticorrosive effect of fly ash was determined with measurements of open porosity and sorptivity, calculation of chloride concentration and mass loss of steel reinforcement embedded in cement mortars. The experimental results showed that the use of Greek fly ash improves the compressive strength and elastic modulus of concrete at all ages. Moreover, the porosity and sorptivity were decreased in the presence of the aforementioned additive. In addition, the theoretical mass loss of steel reinforcement embedded in cement mortars with 5% w.w fly ash addition was equal to that of reference concrete after 13months of exposure in sodium chloride environment.
‘Snow White and the Seven Dwarfs’, a fairytale that is widely known across the Western world, was originally written by the Brothers Grimm, and published in 1812 as ‘Snow White’. Though each dwarf was first given an individual name in the 1912 Broadway play, in Walt Disney ’s 1937 film ‘Snow White and the Seven Dwarfs’ , they were renamed, and the dwarfs have become household names. It is well known that myths, fables, and fairytales, though appearing to be merely children’s tales about fictional magical beings and places, have, more often than not, originated from real facts. Therefore, the presence of the seven brothers with short stature in the story is, from an endocrinological point of view, highly intriguing, in fact, thrilling. The diversity of the phenotypes among the seven dwarfs is also stimulating, although puzzling. We undertook a differential diagnosis of their common underlying disorder based on the original Disney production’s drawings and the unique characteristics of these little gentlemen, while we additionally evaluated several causes of short stature and, focusing on endocrine disorders that could lead to these clinical features among siblings, we have, we believe, been able to reveal the underlying disease depicted in this archetypal tale.
Abstract: Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.
