Reconstruction of the Łazienkowski Bridge in Warsaw

W październiku 2015 roku przywrócono ruch samochodowy na odbudowanym Moście Łazienkowskim w Warszawie. Pomimo faktu, iż nie wszystkie prace budowlane zostały jeszcze zakończone, uznaliśmy, że na tym etapie budowy Projektanci powinni przedstawić swój punkt widzenia. Pojawiające się w mediach i środowisku mostowym pytania, uwagi i wątpliwości wymagają naszym zdaniem wyjaśnienia. Wiemy, że skala tego zdarzenia, jego społeczne konsekwencje oraz czas i sposób odbudowy mostu będą jeszcze nie raz omawiane i dyskutowane przy różnych okazjach. Sprawa samego pożaru, jego przebiegu i skutków będzie z pewnością wnikliwie i szczegółowo omówiona przez autorów ekspertyzy spalonej konstrukcji. Również członkowie konsorcjum firm wykonawczych prowadzących odbudowę na pewno będą przedstawiać proces samej budowy. W tym artykule skupimy się na kwestiach projektowych. Spróbujemy opisać tok prac nad projektem i wyjaśnić nasze wybory. Z kilku pomysłów rozwiązań konstrukcyjnych wybrano ostatecznie schemat dwudźwigarowy o przekrojach skrzynkowych i wysokości konstrukcyjnej 1/20 rozpiętości, mniejszej o 0.40 m od istniejących. Dźwigary ustawiono na łożysku w osi istniejących filarów w rozstawie 15.70 m i połączono poprzecznicami płyty ortotropowej rozmieszczonymi co 3.75 m (poprzednio co 2.5 m). Pod zwiększonymi wspornikami chodników pozostawiono przestrzeń dla umieszczenia pomostów dwóch ścieżek rowerowych o szerokości 3.4 m każda a w przestrzeni pomiędzy dźwigarami pozostawiono jednoprzestrzenną strefę dla montażu wszystkich urządzeń obcych i zapewnienie przestrzeni, wymaganej przez gestorów, dla ich obsługi (min. tor dla wózka rewizyjnego do wymiany rur ciepłociągów).In October 2015 the road traffic on the reconstructed Łazienkowski Bridge in Warsaw was renewed. Despite the fact, that not all reconstructive works have been completed, Designers decided to present their point of view. In our opinion, the questions, remarks and doubts presented in mass médias need to be clarified. We realize, that the scale of the event, its social consequences and the period and method of the bridge reconstruction will be discussed in various occasions many times in the future. The fire itself, its spreading and consequences will be for sure thoroughly and in detail described by the experts examining the burnt structure. Also, the members of the consortium carrying out the reconstruction works will be presenting the construction process. In this article, we focus on the designing issues. We will try to describe the designing process and clarify our decisions. From among several construction solutions, finally the two-girder scheme with box cross-sections and the structural height of 1/20 of the span length (smaller by 0,40 m in relation to the existing ones), was selected. The girders, spaced by 15,70 m, were located on the bearing in the axis of the existing pillars, and were joined with diaphragms of the orthotropic plate, spaced every 3,75 m (previously every 2,5 m). Under the lengthened sidewalk cantilevers, the space for platforms with two bicycle paths 3,4 m wide each, was left. The space between the girders was designated for all infrastructure devices and, required by their owners, their maintenance and service (among the others, the track for the inspection truck for replacement of the hot-water pipeline)

International Waist Circumference Percentile Cutoffs for Central Obesity in Children and Adolescents Aged 6 to 18 Years.

No universal waist circumference (WC) percentile cutoffs used have been proposed for screening central obesity in children and adolescents. To develop international WC percentile cutoffs for children and adolescents with normal weight based on data from 8 countries in different global regions and to examine the relation with cardiovascular risk. We used pooled data on WC in 113,453 children and adolescents (males 50.2%) aged 4 to 20 years from 8 countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cutoffs in samples including or excluding children with obesity, overweight, or underweight. WC percentiles were generated using the general additive model for location, scale, and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cutoffs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from 3 countries that had available data (China, Iran, and Korea). We also examined which WC percentiles linked with WC cutoffs for central obesity in adults (at age of 18 years). WC measured based on recommendation by the World Health Organization. We validated the performance of the age- and sex-specific 90th percentile WC cutoffs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight, or underweight) by linking the percentile with cardiovascular risk (area under the curve [AUC]: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cutoffs for central obesity in adults (eg, AUC in US adolescents: 0.71 for boys; 0.68 for girls). The international WC cutoffs developed in this study could be useful to screen central obesity in children and adolescents aged 6 to 18 years and allow direct comparison of WC distributions between populations and over time

Molecular targets of cannabidiol in neurological disorders

Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD’s beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular phar- macology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD’s relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeu- tics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent with modulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug’s action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excluding unlikely and implausible targets, the remaining molecular targets of CBD with plausible evidence for involvement in therapeutic effects in neurological disorders (e.g., voltage-dependent anion channel 1, G protein-coupled receptor 55, CaV3.x, etc.) are associated with either the regulation of, or responses to changes in, intracellular calcium levels. While no causal proof yet exists for CBD’s effects at these targets, they represent the most probable for such investigations and should be prioritized in further studies of CBD’s therapeutic mechanism of action

Biochemical and pharmacological role of A1adenosine receptors and their modulation as novel therapeutic strategy

Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2Band A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers. Several lines of evidence indicate that adenosine interacting with A1ARs may be an endogenous protective agent in the human body since it prevents the damage caused by various pathological conditions, such as in ischemia/hypoxia, epileptic seizures, excitotoxic neuronal injury and cardiac arrhythmias in cardiovascular system. It has also been reported that one of the most promising targets for the development of new anxiolytic drugs could be A1ARs, and that their activation may reduce pain signaling in the spinal cord. A1AR antagonists induce diuresis and natriuresis in various experimental models, mediating the inhibition of A1ARs in the proximal tubule which is primarily responsible for reabsorption and fluid uptake. In addition, the results of various studies indicate that adenosine is present within pancreatic islets and is implicated through A1ARs in the regulation of insulin secretion and in glucose concentrations. In the present paper it will become apparent that A1ARs could be implicated in the pharmacological treatment of several pathologies with an important influence on human health