Maturation of cytochrome P450 3A mediated drug metabolism: Towards individualized dosing in children

__Abstract__ Most drugs have not been adequately studied in children, leaving this population at an increased risk of underdosing or toxicity. Because of ethical, practical and financial constraints of pediatric clinical trials, there is a high percentage of drugs that is used in an unlicensed or off-label manner, with percentages approximating 70% in children and more than 93% in critically ill neonates. The main limitations in designing and conducting clinical studies in children are ethical, practical and scientific. Ethical issues are e.g. proxy consent, safety concerns and blood volume needed for pharmacokinetics. Practical issues pertain to the limited number of patients available and sample collection challenges. Scientific issues are related to the impact of growth and development on drug disposition, while increasingly attention is put on the long-term impact of early-life drug exposure on the developing brain. In the past the emphasis has been on the evaluation of the short-term direct effects of drugs, such as the increase in blood pressure upon the administration of vasoactive drugs. Fortunately, the current interest in primary outcome measures of drug treatment has led to an increase in the number of studies investigating long-term effects, i.e. neurodevelopmental outcome in children. An example is the recent study in which long-term cardiovascular effects of dobutamine and dopamine have been compared in preterm and low birth weight neonates

A parallel algorithm for the enumeration of benzenoid hydrocarbons

We present an improved parallel algorithm for the enumeration of fixed benzenoids B_h containing h hexagonal cells. We can thus extend the enumeration of B_h from the previous best h=35 up to h=50. Analysis of the associated generating function confirms to a very high degree of certainty that $B_h \sim A \kappa^h /h$ and we estimate that the growth constant $\kappa = 5.161930154(8)$ and the amplitude $A=0.2808499(1)$.Comment: 14 pages, 6 figure

Peningkatan Produksi dan Analisis Kelayakan Usaha Padi Sawah dengan Sistem Pengelolaan Tanaman Terpadu (PTT)

This study aims to determine the growth and productivity of low land rice, Inpari 14 variety managed under the integrated farming system (PTT) and to conduct its feasibility analysis with the same system. The research used Randomized Block Design (RBD) non factorial consisting of 9 treatments and 3 replications. The treatments used, namely: control (“square” style of plant spacing 20cm x 20cm, transplanting 17 days after sowing, 3 seedlings per planting hole, and no manure); PTT 1 (square plant spacing 20cm x 20cm, transplanting 15 days after sowing, one seedling per planting hole, and 1 t ha-1 manure); PTT 2 (“legowo style” of plant spacing of 2:1, transplanting 15 days after sowing, planting one seedling per planting hole, and 1 t ha-1 manure); PTT 3 (square plant spacing of 20cm x 20cm, transplanting 15 days after sowing, 2 seedlings, and 1 t ha-1 manure); PTT 4 (legowo spacing of 2:1, transplanting 15 days after sowing, planting 2 seeds per planting hole, and 1 t ha-1 manure); PTT 5 (square planting spacing of 20cm x 20cm, transplanting 15 days after sowing, planting one seed per planting hole , and 2 t ha-1 manure); PTT 6 (legowo spacing 2:1, transplanting 15 days after sowing, planting one seed per planting hole, and 2 t ha-1 manure); PTT 7 (square planting spacing of 20cm x 20cm, transplanting 15 days after sowing, 2 seeds per planting hole, and 2 t ha-1 manure), and PTT 8 (legowo spacing of 2:1, transplanting 15 days after sowing, 2 seeds per planting hole, and 2 t ha-1 manure). Results showed that an increase in production of 0.9 t ha-1 or 17.33 percent of the rice attained by PTT 8 treatment compared to the control with each production 5.25 t ha-1 and 4.34 t ha-1. There were trends that the dried husk rice results ha-1 of legowo cropping systems, namely PTT 2 (4.96 t ha-1), PTT 4 (5.21 t ha-1) , PTT 6 (4.13 t ha-1), and PTT 8 (5.25 t ha-1) had a higher yield than the PTT tile systems treatment, namely PTT 1 (3.18 t ha-1); PTT3 ( 4.13 t ha-1); PTT 5 (4.17 t ha-1), and PTT 7 (4.19 t ha-1). The PTT 8 treatment gave profit per hectare of Rp. 16,171,057 (Sixteen Million One Hundred Seventy One Thousand Fifty Seven Rupiah) that was higher compared to control of Rp. 13,002,557 (Thirteen Million Two Thousand Five Hundred Fifty Seven Rupiah) that mean the PTT 8 treatment provided increased revenue by 20

Sustainable upgrading of glycerol into glycidol and its derivatives under continuous-flow conditions

This study presents a continuous-flow process for the valorization of glycerol, a byproduct of the biofuel industry, into glycidol and its derivatives. The method ensures safety and allows for easy production of glycidol on a gram scale, even in the presence of hazardous substances such as hydrogen chloride and acetic acid. Moreover, this continuous-flow method can be easily integrated with downstream synthetic steps to produce value-added derivatives, which have potential applications in the fields of medicinal and polymer chemistry. The comprehensive evaluation of sustainability metrics, encompassing green indicators, a techno-economic analysis, and a life cycle assessment, substantiates the environmental benefits of the technology, and showed that the method is environmentally friendly and has the potential to enhance efficiency, safety, and sustainability in industrial processes

On the Linearization of the Painleve' III-VI Equations and Reductions of the Three-Wave Resonant System

We extend similarity reductions of the coupled (2+1)-dimensional three-wave resonant interaction system to its Lax pair. Thus we obtain new 3x3 matrix Fuchs--Garnier pairs for the third and fifth Painleve' equations, together with the previously known Fuchs--Garnier pair for the fourth and sixth Painleve' equations. These Fuchs--Garnier pairs have an important feature: they are linear with respect to the spectral parameter. Therefore we can apply the Laplace transform to study these pairs. In this way we found reductions of all pairs to the standard 2x2 matrix Fuchs--Garnier pairs obtained by M. Jimbo and T. Miwa. As an application of the 3x3 matrix pairs, we found an integral auto-transformation for the standard Fuchs--Garnier pair for the fifth Painleve' equation. It generates an Okamoto-like B\"acklund transformation for the fifth Painleve' equation. Another application is an integral transformation relating two different 2x2 matrix Fuchs--Garnier pairs for the third Painleve' equation.Comment: Typos are corrected, journal and DOI references are adde

Honeycomb lattice polygons and walks as a test of series analysis techniques

We have calculated long series expansions for self-avoiding walks and polygons on the honeycomb lattice, including series for metric properties such as mean-squared radius of gyration as well as series for moments of the area-distribution for polygons. Analysis of the series yields accurate estimates for the connective constant, critical exponents and amplitudes of honeycomb self-avoiding walks and polygons. The results from the numerical analysis agree to a high degree of accuracy with theoretical predictions for these quantities.Comment: 16 pages, 9 figures, jpconf style files. Presented at the conference "Counting Complexity: An international workshop on statistical mechanics and combinatorics." In celebration of Prof. Tony Guttmann's 60th birthda

Helical Magnetorotational Instability in Magnetized Taylor-Couette Flow

Hollerbach and Rudiger have reported a new type of magnetorotational instability (MRI) in magnetized Taylor-Couette flow in the presence of combined axial and azimuthal magnetic fields. The salient advantage of this "helical'' MRI (HMRI) is that marginal instability occurs at arbitrarily low magnetic Reynolds and Lundquist numbers, suggesting that HMRI might be easier to realize than standard MRI (axial field only). We confirm their results, calculate HMRI growth rates, and show that in the resistive limit, HMRI is a weakly destabilized inertial oscillation propagating in a unique direction along the axis. But we report other features of HMRI that make it less attractive for experiments and for resistive astrophysical disks. Growth rates are small and require large axial currents. More fundamentally, instability of highly resistive flow is peculiar to infinitely long or periodic cylinders: finite cylinders with insulating endcaps are shown to be stable in this limit. Also, keplerian rotation profiles are stable in the resistive limit regardless of axial boundary conditions. Nevertheless, the addition of toroidal field lowers thresholds for instability even in finite cylinders.Comment: 16 pages, 2 figures, 1 table, submitted to PR

Between the witness and the observer: what ethnography can learn from James Baldwin

What is the role of the ethnographer during a time of increased racial hostility, political mobilization to keep racial minorities “in their place,” and commitments to revisionist interpretations of the country's past and projected future? While the traditional, classic ethnographic approach would recommend that the researcher should avoid taking a stance on so-called political matters and merely observe them, I argue that that position is insufficient to address the issues that people are currently facing. Ethnography can, and should, do more. Therefore, this essay argues that the role of the ethnographer should be oriented toward what the late author James Baldwin calls the witness. The witness is different from the observer because it rejects a positivistic orientation toward ethnographic fieldwork that prioritizes spectatorship to remain “scientific.” To be a witness is to transgress traditional epistemological understandings of ethnography that ignores how the researcher's position within the racial system shapes how one knows and does not know, what one sees and does not see, and how one imagines freedom and justice. Ethnographers can learn from Baldwin's method because it provides a rich vocabulary to describe the inequality that research participants encounter while in the field and embraces the possibility of an apocalyptic future, which is a future that is not guaranteed if we continue to seek neutrality. In this article, I detail three lessons that we can learn from Baldwin's method and status position as the witness: (1) Connecting empire to the global racial order via the international outsider; (2) Paying one's dues as a within-nation outsider; and (3) Representing the wretched as a within-community outsider. These lessons are instructive for ethnographers because they provide a lens to understand classic ethnographies of the past, while not wallowing in the doldrums of present arrangements, and challenges future research to ground reality as it is rather than what it “should” be

Bound State Wave Functions through the Quantum Hamilton - Jacobi Formalism

The bound state wave functions for a wide class of exactly solvable potentials are found utilizing the quantum Hamilton-Jacobi formalism. It is shown that, exploiting the singularity structure of the quantum momentum function, until now used only for obtaining the bound state energies, one can straightforwardly find both the eigenvalues and the corresponding eigenfunctions. After demonstrating the working of this approach through a number of solvable examples, we consider Hamiltonians, which exhibit broken and unbroken phases of supersymmetry. The natural emergence of the eigenspectra and the wave functions, in both the unbroken and the algebraically non-trivial broken phase, demonstrates the utility of this formalism.Comment: replaced with the journal versio