On Intergenerational Transmission of Reading Habits in Italy: Is a Good Example the Best Sermon?

The intergenerational transmission of preference and attitudes has been less investigated in the literature than the intergenerational transmission of education and income. Using the Italian Time Use Survey (2002-2003) conducted by ISTAT, we analyse the intergenerational transmission of reading habits: are children more likely to allocate time to studying and reading when they observe their parents doing the same activity? The intergeneration transmission of attitudes towards studying and reading can be explained by both cultural and educational transmission from parents to children and by imitating behaviours. The latter channel is of particular interest, since it entails a direct influence parents may have on child’s preference formation through their role model, and it opens the scope for active policies aimed at promoting good parents’ behaviours. We follow two fundamental approaches to estimation: a “long run” model, consisting of OLS intergenerational type regressions for the reading habit, and “short run” household fixed effect models, where we aim at identifying the impact of the role model exerted by parents, exploiting different exposure of sibling to parents’ example within the same household. Our long run results show that children are more likely to read and study when they live with parents that are used to read. Mothers seem to be more important than fathers in this type of intergenerational transmission. Moreover, the short run analysis shows that there is an imitation effect: in the day of the survey children are more likely to read after they saw either the mother or the father reading.

Understanding How the Platinum Anticancer Drug Carboplatin Works: From the Bottle to the Cell

Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer-dimer equilibrium with an association constant of K (M -1) ≈ 391, a property that accounts for the long-term stability of its ready-to-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO 3 2- (k 1 = 2.04 ± 0.81 × 10 -6 in 24 mM carbonate buffer, pH 7.5 at 37 °C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system

Understanding how the platinum anticancer drug carboplatin works: From the bottle to the cell

Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer–dimer equilibrium with an association constant of K (M−1) ≈ 391, a property that accounts for the long-term stability of its ready-to-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO32− (k1 = 2.04 ± 0.81 × 10−6 in 24 mM carbonate buffer, pH 7.5 at 37 °C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns : impact of design optimisation

Purpose: There is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates. Methods: A published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a first-in-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study. Results: Parameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA. Conclusions: The use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population

Pharmacokinetics of plasma infusion in congenital thrombotic thrombocytopenic purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) is defined by persistent severe deficiency of ADAMTS-13 in the absence of anti-ADAMTS-13 inhibitory antibodies, confirmed by mutational analysis. Replacement of the missing protease prevents disease relapse, primarily using plasma infusion (PI). OBJECTIVES, PATIENTS AND METHODS: There is scant evidence regarding optimal dose and frequency of treatment, tending to be empirically guided. We present a pharmacokinetic analysis of ADAMTS-13 in 6 patients with congenital TTP on established regimes following PI. RESULTS: We found a median clearance of 25.41ml/h and half-life of 130 hours, ranging between 82.6 and 189.5 hours (3.4 to 7.9 days respectively). All patients reached baseline ADAMTS-13 level within 7-10 days post plasma. Median ADAMTS-13 activity peak post PI was 24.05IU/dL. Variation was related to elimination rate, in turn affected by weight and metabolism, but not to von Willebrand factor antigen or activity levels. Using the pharmacokinetic parameters, we simulated individualised protocols based on PI dose or frequency to target hypothetical optimal plasma levels of ADAMTS-13 of 10 and 50IU/dL respectively. Results suggest a target trough ADAMTS-13 of 10IU/dL is feasible but 50IU/dL would not be achievable taking into account volume required. CONCLUSIONS: Further work is needed to compare treatment of congenital TTP with PI versus recombinant ADAMTS-13. PI may provide longer duration of ADAMTS-13 effect, but is limited by plasma volume required, whereas recombinant therapy can provide a higher ADAMTS-13 peak. We propose that investigation of interindividual clearance of ADAMTS-13 is necessary to optimise treatment, to enable rationale for dose and frequency of prophylaxis

A Hidden Twelve-Dimensional SuperPoincare Symmetry In Eleven Dimensions

First, we review a result in our previous paper, of how a ten-dimensional superparticle, taken off-shell, has a hidden eleven-dimensional superPoincare symmetry. Then, we show that the physical sector is defined by three first-class constraints which preserve the full eleven-dimensional symmetry. Applying the same concepts to the eleven dimensional superparticle, taken off-shell, we discover a hidden twelve dimensional superPoincare symmetry that governs the theory.Comment: 13 page

Two cases study of fouling colonization patterns in the Mediterranean Sea in the perspective of integrated aquaculture systems

Fouling assemblage colonizing fish-farms is considered mostly to produce negative impacts causing financial loss. By contrast, large evidences emerged on the bioremediation role by biofouling associated to aquaculture facilities, even if the fouling assemblages thriving in the water column was poorly investigated. The aim of the present work was to investigate the macrofouling assemblages over one year of immersion, in order to single out the fouling species, which play the most remarkable role for the bioremediation of the marine areas affected by aquaculture activities. With this in mind, we studied the fouling community dynamics in two Mediterranean maricultural facilities, respectively in the Mar Grande of Taranto (Ionian Sea) and in the Gulf of Gaeta (Tyrrhenian Sea), using the same experimental design and time frame. Two experiments were carried out using artificial panels anchored to two finfish cages. The one-year old fouling communities in the two sites were compared at four seasons of immersion, four submersion durations and three depths, both communities from structural and functional points of view. Notwithstanding the quite similar species composition of fouling of the two sites, the biofouling showed the highest biodiversity in the Mar Grande of Taranto. In the Gulf of Gaeta mussels, Mytilus galloprovincialis, dominated at all the times and depths, whilst in the Mar Grande of Taranto they were especially abundant at the surface with the deepest panels being largely colonized by polychaete sabellids. The co-occurrence of the filter-feeders Mytilus-sabellids recorded in the Gulf of Taranto also highlighted the highest filtration capability. Our results suggest two different fouling assemblages as candidates for bioremediation in integrated multitrophic aquaculture facilities: both a monospecific system dominated by mussels and a multi-specific system with sabellids and mussels as most abundant filter-feeders

Spectrofluorometric analysis of autofluorescing components of crude serum from a rat liver model of ischemia and reperfusion

Autofluorescence (AF) of crude serum was investigated with reference to the potential of its intrinsic AF biomarkers for the noninvasive diagnosis of liver injury. Spectral parameters of pure compounds representing retinol (vitamin A) and fluorescing free fatty acids were characterized by spectrofluorometry, to assess spectral parameters for the subsequent AF analysis of serum, collected from rats undergoing liver ischemia/reperfusion (I/R). Differences in AF spectral profiles detected between control and I/R were due to the increase in the AF components representing fatty acids in I/R serum samples. No significant changes occurred for retinol levels, consistently with the literature reporting that constant retinol levels are commonly observed in the blood, except for malnutrition or chronic severe liver disease. Conversely, fatty acids, in particular arachidonic and linoleic acid and their derivatives, act as modulating agents in inflammation, representing both a protective and damaging response to stress stimuli. The biometabolic and pathophysiological meaning of serum components and the possibility of their direct detection by AF spectrofluorometry open up interesting perspectives for the development of AF serum analysis, as a direct, cost effective, supportive tool to assess liver injury and related systemic metabolic alterations, for applications in experimental biomedicine and foreseen translation to the clinics

Stability of Carboplatin and Oxaliplatin in their Infusion Solutions is Due to Self-Association

Carboplatin and oxaliplatin are commonly used platinum anticancer agents that are sold as ready-to-use aqueous infusion solutions with shelf lives of 2 and 3 years, respectively. The observed rate constants for the hydrolysis of these drugs, however, are too large to account for their long shelf lives. We here use electrospray-trap mass spectrometry to show that carboplatin and oxaliplatin are self-associated at concentrations in their ready-to-use infusion solutions (∼27 mM and 13 mM, respectively) and, as expected, when the drug concentration is reduced to more physiologically relevant concentrations (100 μM and 5 μM, respectively) the association equilibrium is shifted in favor of the monomeric forms of these drugs. Using 1H NMR we measure the intensity of the NH resonance of the two symmetry-equivalent NH 3 molecules of carboplatin, relative to the intensity of the γ-methylene CH resonance, as a function of total drug concentration. Then, by fitting the data to models of different molecularity, we show that the association complex is a dimer with a monomer-dimer association constant of K (M -1) = 391 ± 127. The work presented here shows that carboplatin and oxaliplatin mainly exist as association complexes in concentrated aqueous solution, a property that accounts for the long term stability of their ready-to-use infusion solutions, and that these association complexes may exist, to some extent, in the blood after injection