Direct Extrapolation Research Articles

Maternal intermittent fasting during pregnancy: a translational research challenge for an important clinical scenario.

In volume 135, issue 11 of Clinical Science, Alkhalefah et al. report that, in pregnant rats, repeated, cyclic fasting, mimicking the fasting experienced by observant Muslim pregnant women during Ramadan, alters placental amino acid transport and increases the incidence of low birth weight. Though Muslim women are exempt, many observe Ramadan: >500 million fetuses worldwide may be exposed to Ramadan fasting in each generation, and low birth weight increases the risk of developing chronic disease in the future adult. Several mechanisms, including altered circadian rhythm, maternal stress, undernutrition or compensatory overeating at the breaking of fast, could, in theory, impact fetal growth during Ramadan. Limitations of the experimental model obviously prevent direct extrapolation to humans. Whether Ramadan fasting indeed affect fetal growth therefore remains unclear, as there is no clear-cut evidence from epidemiological studies. The paper illustrates the need to design further case-controlled studies in large cohorts of women who fasted at various stages of pregnancy, compared to appropriately matched women who did not fast, as well as more experimental studies focused on this issue of public health relevance.

Exploring the Complementarity of Pancreatic Ductal Adenocarcinoma Preclinical Models.

Simple SummaryPancreatic ductal adenocarcinoma (PDAC) patient care lacks well-established molecular characterization of the tumors, which would allow for better-personalized treatment selection if improved. To overcome this problem, preclinical models are frequent-ly adopted tools used to elucidate the molecular characterization of PDAC tumors. Unfortunately, the vast majority of studies using these preclinical models fail when transferred to patients despite initially promising results. This study presents for the first time a comparison between three preclinical matched models directly derived from patient tumors. We show that their applicability to preclinical studies should be considered with a complementary focus, avoiding tumor-based direct extrapolations, which might generate misleading conclusions and consequently the overlook of clinically relevant features. We finally highlight the importance of validating and refining predictive transcriptomic signatures using a combination of these models.Purpose: Compare pancreatic ductal adenocarcinoma (PDAC), preclinical models, by their transcriptome and drug response landscapes to evaluate their complementarity. Experimental Design: Three paired PDAC preclinical models—patient-derived xenografts (PDX), xenograft-derived pancreatic organoids (XDPO) and xenograft-derived primary cell cultures (XDPCC)—were derived from 20 patients and analyzed at the transcriptomic and chemosensitivity level. Transcriptomic characterization was performed using the basal-like/classical subtyping and the PDAC molecular gradient (PAMG). Chemosensitivity for gemcitabine, irinotecan, 5-fluorouracil and oxaliplatin was established and the associated biological pathways were determined using independent component analysis (ICA) on the transcriptome of each model. The selection criteria used to identify the different components was the chemosensitivity score (CSS) found for each drug in each model. Results: PDX was the most dispersed model whereas XDPO and XDPCC were mainly classical and basal-like, respectively. Chemosensitivity scoring determines that PDX and XDPO display a positive correlation for three out of four drugs tested, whereas PDX and XDPCC did not correlate. No match was observed for each tumor chemosensitivity in the different models. Finally, pathway analysis shows a significant association between PDX and XDPO for the chemosensitivity-associated pathways and PDX and XDPCC for the chemoresistance-associated pathways. Conclusions: Each PDAC preclinical model possesses a unique basal-like/classical transcriptomic phenotype that strongly influences their global chemosensitivity. Each preclinical model is imperfect but complementary, suggesting that a more representative approach of the clinical reality could be obtained by combining them. Translational Relevance: The identification of molecular signatures that underpin drug sensitivity to chemotherapy in PDAC remains clinically challenging. Importantly, the vast majority of studies using preclinical in vivo and in vitro models fail when transferred to patients in a clinical setting despite initially promising results. This study presents for the first time a comparison between three preclinical models directly derived from the same patients. We show that their applicability to preclinical studies should be considered with a complementary focus, avoiding tumor-based direct extrapolations, which might generate misleading conclusions and consequently the overlook of clinically relevant features.

Comparing the Effect of Different Antibiotics in Frozen-Thawed Ram Sperm: Is It Possible to Avoid Their Addition?

It is crucial to perform a deep study about the most extensively used antibiotics in sperm extenders. Most of the protocols and concentrations used in ram are direct extrapolations from other species. It is important to establish species-specific antibiotic treatments to optimize their use and if it is possible to reduce the quantity. Previews studies have assessed some aspects of sperm quality in vitro, but this study aimed to go further and assess the effect of three different antibiotic treatments, which are the most extensively used, not only in sperm quality or assessing the inhibitory effect on bacterial growth but also assessing these important parameters of productivity such as fertility, prolificacy, fecundity, and sex-ratio during a freeze-thaw process. Gentamicyn (G) treatment showed the worst results, not only concerning sperm quality but also in the reproductive trials exhibiting a toxical effect at the experiment concentration, and being the most powerful inhibiting bacterial growth. For its part, Lincomicyn-spectinomycin (LS) showed similar results inhibiting bacterial growth but it did not show a detrimental effect either in sperm quality or in reproductive parameters. Penicillin-streptomycin (PS) showed good results in the sperm quality and in the reproductive in vivo trials, but it showed a very poor effect inhibiting bacterial growth probably due to some kind of antibiotic resistance. According to our results, there is not a significant positive relationship between the higher bacterial inhibitory activity of LS and PS samples, and the sperm quality respect Control samples (without antibiotics). In the case of G, which exhibited the most effective as antibacterial, we observed a toxic effect on sperm quality that could be translated on productivity parameters. Our results suggest that the bacterial contamination control in frozen-thawed semen may be possible without the use of antibiotics, although the effects of longer periods of cooling storage and different temperatures of storage need to be further investigated for animal semen. At this point, a reflection about a drastic reduction in the use of antibiotic treatments in sperm cryopreservation is mandatory, since freezing conditions could keep sperm doses contamination within the levels recommended by regulatory health agencies.

Mass-balance and locality versus accuracy with the new boundary and interface-conjugate approaches in advection-diffusion lattice Boltzmann method

We introduce two new approaches, called A-LSOB and N-MR, for boundary and interface-conjugate conditions on flat or curved surface shapes in the advection-diffusion lattice Boltzmann method (LBM). The Local Second-Order, single-node A-LSOB enhances the existing Dirichlet and Neumann normal boundary treatments with respect to locality, accuracy, and Péclet parametrization. The normal-multi-reflection (N-MR) improves the directional flux schemes via a local release of their nonphysical tangential constraints. The A-LSOB and N-MR restore all first- and second-order derivatives from the nodal non-equilibrium solution, and they are conditioned to be exact on a piece-wise parabolic profile in a uniform arbitrary-oriented tangential velocity field. Additionally, the most compact and accurate single-node parabolic schemes for diffusion and flow in grid-inclined pipes are introduced. In simulations, the global mass-conservation solvability condition of the steady-state, two-relaxation-time (S-TRT) formulation is adjusted with either (i) a uniform mass-source or (ii) a corrective surface-flux. We conclude that (i) the surface-flux counterbalance is more accurate than the bulk one, (ii) the A-LSOB Dirichlet schemes are more accurate than the directional ones in the high Péclet regime, (iii) the directional Neumann advective-diffusive flux scheme shows the best conservation properties and then the best performance both in the tangential no-slip and interface-perpendicular flow, and (iv) the directional non-equilibrium diffusive flux extrapolation is the least conserving and accurate. The error Péclet dependency, Neumann invariance over an additive constant, and truncation isotropy guide this analysis. Our methodology extends from the d2q9 isotropic S-TRT to 3D anisotropic matrix collisions, Robin boundary condition, and the transient LBM.

Low energy availability in female athletes: From the lab to the field

ABSTRACT Decades of laboratory research have shown impairments to several body systems after only 4–5 days of strictly controlled consistent low energy availability (LEA); where energy availability (EA) = Energy Intake (EI) − Exercise Energy Expenditure (EEE)/Fat-Free Mass. Meanwhile, cross-sectional reports exist on the interrelatedness of LEA, menstrual dysfunction and impaired bone health in females (the Female Athlete Triad). These findings have demonstrated that LEA is the key underpinning factor behind a broader set of health and performance outcomes, recently termed as Relative Energy Deficiency in Sport (RED-S). There is utmost importance of early screening and diagnosis of RED-S to avoid the development of severe negative health and performance outcomes. However, a significant gap exists between short-term laboratory studies and cross-sectional reports, or clinically field-based situations, of long-term/chronic LEA and no definitive, validated diagnostic tests for RED-S exist. This review aims to highlight methodological challenges related to the assessment of the components of EA equation in the field (e.g. challenges with EI and EEE measures). Due to the uncertainty of these parameters, we propose the use of more chronic “objective” markers of LEA (i.e. blood markers). However, we note that direct extrapolations of laboratory-based outcomes into the field are likely to be problematic due to potentially poor ecological validity and the extreme variability in most athlete’s daily EI and EEE. Therefore, we provide a critical appraisal of the scientific literature, highlighting research gaps, and a potential set of leading objective RED-S markers while working in the field. Highlights Direct application of short-term laboratory-based findings in the field is problematic. Calculation of energy availability (EA) in the field is methodologically challenging and prone to errors. The use of several biomarkers may allow the detection of early exposure to low EA in the female athlete.

A Simple New Way To Account for Free Volume in Glassy Dynamics: Model-Free Estimation of the Close-Packed Volume from PVT Data.

In this article we focus on the important role of well-defined free volume (Vfree) in dictating the structural relaxation times, τ, of glass-forming liquids and polymer melts. Our definition of Vfree = V - Vhc, where V is the total system volume, means the use of Vfree depends on determination of Vhc, the system's volume in the limiting closely packed state. Rejecting the historically compromised use of Vfree as a dynamics-dependent fitting function, we have successfully applied a clear thermodynamics-based route to Vhc using the locally correlated lattice (LCL) model equation of state (EOS). However, in this work we go further and show that Vhc can be defined without the use of an equation of state by direct linear extrapolation of a V(T) high-pressure isobar down to zero temperature (T). The results from this route, tested on a dozen experimental systems, yield ln τ vs 1/Vfree isotherms that are linear with T-dependent slopes, consistent with the general ln τ ∼ f(T) × (1/Vfree) form of behavior we have previously described. This functional form also results by implementing a simple mechanistic explanation via the cooperative free volume (CFV) rate model, which assumes that dynamic relaxation is both thermally activated and that it requires molecular segmental cooperativity. With the degree of the latter, and thus the activation energy, being determined by the availability of free volume, the new route we demonstrate here for determination of Vfree expands the potential for understanding and predicting local dynamic relaxation in glass-forming materials.

A Method of the Lagrange Polynomial Interpolation with Weighting Factors for Reducing Computational Time

This paper proposes a novel extrapolation method known as the Lagrange polynomial interpolation with weighting factors (LPI-WF) to determine initial guess values in each time step for solving equation systems of transient problems using iterative methods. The LPI-WF method is developed from the Lagrange polynomial interpolation to determine the direct extrapolation values and multiply them with the weighting factors. The weighting factors are calculated by considering the number of the previous time steps involved in the extrapolation and the duration between the present time step and the previous time steps. Thus, the LPI-WF method is proper for use with highorder temporal schemes. The key advantages of the LPI-WF method are that the computational time required to achieve the steady-state condition of the transient problems is reduced and the computation codes with the LPI-WF method is more stable than without the LPI-WF method at high time step values. A performance test of the LPI-WF method is carried out by comparing the computational time based on the “lid-driven cavity flow” problem for Reynolds numbers of 1000 and 5000. The test result shows that the computational time of the problem when the LPI-WF method is adopted can be reduced up to 10.46 % compared to the conventional method.

Pregnancy-specific physiologically-based toxicokinetic models for bisphenol A and bisphenol S

Predictions from physiologically based toxicokinetic (PBTK) models can help inform human health risk assessment for potentially toxic chemicals in the environment. Bisphenol S (BPS) is the second most abundant bisphenol detected in humans in the United States, after bisphenol A (BPA). We have recently demonstrated that BPS, much like BPA, can cross the placental barrier and disrupt placental function. Differences in physicochemical properties, toxicokinetics, and exposure outcomes between BPA and other bisphenols prevent direct extrapolation of existing BPA PBTK models to BPS. The current study aimed to develop pregnancy-specific PBTK (p-PBTK) models for BPA and BPS, using a common p-PBTK model structure. Novel paired maternal and fetal pregnancy data sets for total, unconjugated, and conjugated BPA and BPS plasma concentrations from three independent studies in pregnant sheep were used for model calibration. The nine-compartment (maternal blood, liver, kidney, fat, placenta and rest of body, and fetal liver, blood and rest of body) models simulated maternal and fetal experimental data for both BPA and BPS within one standard deviation for the majority of the experimental data points, highlighting the robustness of both models. Simulations were run to examine fetal exposure following daily maternal exposure to BPA or BPS at their tolerable daily intake dose over a two-week period. These predictive simulations show fetal accumulation of both bisphenols over time. Interestingly, the steady-state approximation following this dosing strategy achieved a fetal concentration of unconjugated BPA to levels observed in cord blood from human biomonitoring studies. These models advance our understanding of bisphenolic compound toxicokinetics during pregnancy and may be used as a quantitative comparison tool in future p-PBTK models for related chemicals.

OP520 Evaluating Long-Term Survival From Clinical Trials: Does Real-World Evidence Change the Paradigm?

IntroductionBoth patient composition and medical care received in clinical trials may not be representative of clinical practice, yet health technology assessments (HTAs) commonly use extrapolation results from trials to estimate incremental benefit. Due to data limitations, external validation of trial extrapolations are uncommon. With the goal of better estimating the benefit of new therapies in practice, we compared long-term survival estimated from real-world patients who received therapy similar to the comparator arm of the OAK trial, a phase III study of patients with advanced non-small cell lung cancer (aNSCLC) who progressed following initial chemotherapy, to standard estimation approaches.MethodsWe estimated long-term survival from: (i) direct extrapolation of trial survival curves; and (ii) aNSCLC patients from the United States Flatiron Health Electronic Health Record ()-derived de-identified database diagnosed between January 2011 and August 2019 who received docetaxel monotherapy after platinum-doublet and had adequate organ function as well as functional status. Patients with unknown organ function and functional status were also included. Standard parametric extrapolations were applied and selected based on visual inspection and goodness-of-fit tests for each cohort.ResultsUsing a log-logistic model to extrapolate the trial comparator arm (N = 425), estimated lifetime mean overall survival was 19.2 months (95% confidence interval [95% CI]: 16.5–22.6), and 14.4 months (95% CI: 12.4–17.0) for the real-world cohort (N = 415). Estimated 5-year overall survival rates were 5.4 percent (95% CI: 3.9–7.3) for the trial patients, compared to 3.7 percent (95% CI: 2.6–5.0) among real-world cohort patients.ConclusionsOur results suggest that directly extrapolating observed survival for trial patients may overestimate the long-term survival compared to the experience of patients treated in routine practice. Our findings have implications for those wishing to estimate the incremental benefit for novel versus established treatments. We plan to compare our results to a generic patient cohort from national cancer registry. Further EHR-based studies utilizing real world data are needed to confirm our findings and to extend beyond this use case for other cancer types and anti-neoplastic therapies.

Photocatalytic and biological oxidation treatment of real textile wastewater

In this study, the discoloration of wastewater containing azo dyes by chemical oxidation process combined with a biological treatment was evaluated and applied to real textile wastewater generated from one Ethiopian industrial site. The use of TiO2 as photocatalyst and the effect of the addition of H2O2 on color removal was first investigated. Photocatalysis was followed by aerobic biological treatment, and their combination resulted in a high extent of color removal (93.3%) and chemical oxygen demand (COD) reduction (90.4%). This was reached without pH correction and with low energy consumption compared to the implementation of AOPs alone. This study performed with real textile wastewater allows the direct extrapolation of the data for the design of a cost-effective and applicable treatment procedure at a pilot scale.Graphic abstract

Direct extrapolation techniques on the energy band diagram of BiVO4 thin films

Bismuth vanadate (BiVO4) is one of the n-type semiconductors which has attracted attention as one of the promising photoanodes semiconductor for photoelectrochemical water splitting due to its small optical band gap, low cost, negative conduction band edge and good stability. In this work, BiVO4 thin films is fabricated by using electrodeposition method and the XRD spectra reveal that the sample crystallizes in monoclinic scheelite type. The optical bands show the bandgap energy of BiVO4 thin films is 2.40 eV as determined by Tauc plot and exhibits an anodic photocurrent. Further study is focusing on determination of the conduction band (CB) and valence band (VB) of BiVO4 thin films which is derived experimentally by using XPS analysis, Mott–Schottky plot and Cyclic Voltammetry (CV) technique. Based on the results, it is found that different analysis techniques exhibit almost similar values of CB and VB of BiVO4 thin films. All techniques give VB maximum in the range of 2.02 eV–2.05 eV and CB minimum in the range of −0.35 eV to −0.39 eV. However, the flat-band potential determined from Mott–Schottky plot is nearly 0.1 eV from CB potential caused by the presence of Fermi level and the effect of Helmholtz capacitance for dielectric semiconductors. These findings clearly show that the experimental values of different analysis techniques give comprehensive approach to understanding the energy band structure of the BiVO4 thin films.

Albumin-Mediated Uptake Improves Human Clearance Prediction for Hepatic Uptake Transporter Substrates Aiding a Mechanistic In Vitro-In Vivo Extrapolation (IVIVE) Strategy in Discovery Research.

This study focused on exploring various in vitro to in vivo extrapolation (IVIVE) approaches with the primary goal of improving human hepatic clearance (CL) prediction for OATP substrates. To that effect, the impact of albumin-mediated uptake in human hepatocytes was investigated. In vitro hepatic uptake assay using suspended human hepatocytes was performed with 16 selected OATP substrates to determine the uptake CL in the absence and presence of 4% BSA and unbound hepatocyte to media partition coefficient (Kpuu). Substantial enhancement of the unbound uptake CL (PSu,inf) was observed in the presence of 4% BSA, demonstrating "albumin-mediated" uptake. Prediction of human hepatic CL was performed using two non-traditional IVIVE approaches: initial uptake CL (PSu,inf) and intrinsic metabolic CL (CLint,met) corrected by Kpuu based on extended clearance concept. Compared to traditional IVIVE using CLint,met only, the two tested IVIVE approaches significantly improved the prediction of human hepatic CL. Particularly, direct extrapolation from PSu,inf (+BSA) showed the most robust correlation with in vivo human hepatic CL for all 16 compounds with bias of 1.9-2.0 for two lots of human hepatocytes, respectively. In addition, PSu,inf (+BSA) and Kpuu were also determined in suspended cynomolgus monkey hepatocytes. Prediction of monkey hepatic CL was improved by both approaches, although with more bias compared to human. These results suggested supplementing 4% BSA in human hepatocyte uptake assay provides a useful tool to characterize hepatic uptake CL for OATP substrates, enabling more accurate human CL prediction without any empirical scaling factor (ESF).

Первичный центр детского инсульта на базе многопрофильного педиатрического стационара. Новая реальность в педиатрии

Background. The increase in the number of diagnosed strokes in children, significant distinctive features and complexity of diagnosis, treatment and prevention of cerebrovascular diseases in children compared with adults, the impossibility of direct extrapolation of therapeutic recommendations from adult practice to pediatrics required the creation of specialized primary centers of pediatric stroke in Russia. Purpose. The purpose of this article is to describe the experience of organizing a Center for the treatment of children and adolescents with cerebrovascular diseases (hereinafter referred to as the Center) on the basis of the multidisciplinary pediatric hospital of the Morozovskaya Children's City Clinical Hospital of Moscow Healthcare Department, the introduction of modern methods of diagnosis and treatment of strokes in pediatrics, the organization of preventive measures, maintaining the city register of children's stroke, coordinating the provision of medical care to children with cerebrovascular diseases at various levels in the city of Moscow. Materials and methods. The presented experience of organizing and operating the Center covers the period from 2014 to 2019. Researchers used descriptive, statistical, and comparative analysis to demonstrate the Center's performance and justify proposed improvements in diagnostics, management of pediatric patients with cerebrovascular disease, and relapse prevention. Results. In the course of the organization and operation of the Center, there was assessed the frequency of children's strokes in the city: in 2015 - 6.59 cases per 100 thousand of the child population of Moscow; in 2016 - 6.51 per 100 thousand; in 2017 - 6.43 per 100 thousand and in 2018 - 5.86 per 100 thousand. There were improved: the diagnostics of cerebrovascular pathology and its algorithm, modern reperfusion methods of treatment (thrombolysis, thromboextraction) were introduced into practice, outpatient observation. The equipment and trained specialists concentration on the basis of the Center allowed the creation of the Center "full cycle". Maintaining the city register of pediatric stroke made it possible to compare Russian data with those available in the literature and to establish international cooperation with the International Pediatric Stroke Organization. Conclusion. The establishment of the Center is an important example of interdisciplinary interaction in pediatrics. The City Register of Pediatric Stroke will make it possible to assess the problem of childhood stroke in Moscow. The accumulated organizational, medical and diagnostic, scientific, international and educational experience of the Center can be introduced in other regions of the Russian Federation to improve the provision of medical care to children and to solve the most important problem - preserving the health of the country's child population.

Первичный центр детского инсульта на базе многопрофильного педиатрического стационара. Новая реальность в педиатрии

Background. The increase in the number of diagnosed strokes in children, significant distinctive features and complexity of diagnosis, treatment and prevention of cerebrovascular diseases in children compared with adults, the impossibility of direct extrapolation of therapeutic recommendations from adult practice to pediatrics required the creation of specialized primary centers of pediatric stroke in Russia. Purpose. The purpose of this article is to describe the experience of organizing a Center for the treatment of children and adolescents with cerebrovascular diseases (hereinafter referred to as the Center) on the basis of the multidisciplinary pediatric hospital of the Morozovskaya Children’s City Clinical Hospital of Moscow Healthcare Department, the introduction of modern methods of diagnosis and treatment of strokes in pediatrics, the organization of preventive measures, maintaining the city register of children’s stroke, coordinating the provision of medical care to children with cerebrovascular diseases at various levels in the city of Moscow. Materials and methods. The presented experience of organizing and operating the Center covers the period from 2014 to 2019. Researchers used descriptive, statistical, and comparative analysis to demonstrate the Center’s performance and justify proposed improvements in diagnostics, management of pediatric patients with cerebrovascular disease, and relapse prevention. Results. In the course of the organization and operation of the Center, there was assessed the frequency of children’s strokes in the city: in 2015 - 6.59 cases per 100 thousand of the child population of Moscow; in 2016 - 6.51 per 100 thousand; in 2017 - 6.43 per 100 thousand and in 2018 - 5.86 per 100 thousand. There were improved: the diagnostics of cerebrovascular pathology and its algorithm, modern reperfusion methods of treatment (thrombolysis, thromboextraction) were introduced into practice, outpatient observation. The equipment and trained specialists concentration on the basis of the Center allowed the creation of the Center «full cycle». Maintaining the city register of pediatric stroke made it possible to compare Russian data with those available in the literature and to establish international cooperation with the International Pediatric Stroke Organization. Conclusion. The establishment of the Center is an important example of interdisciplinary interaction in pediatrics. The City Register of Pediatric Stroke will make it possible to assess the problem of childhood stroke in Moscow. The accumulated organizational, medical and diagnostic, scientific, international and educational experience of the Center can be introduced in other regions of the Russian Federation to improve the provision of medical care to children and to solve the most important problem - preserving the health of the country’s child population.

Padé and Post-Padé Approximations for Critical Phenomena

We discuss and apply various direct extrapolation methods for calculation of the critical points and indices from the perturbative expansions my means of Padé-techniques and their various post-Padé extensions by means of root and factor approximants. Factor approximants are applied to finding critical points. Roots are employed within the context of finding critical index. Additive self-similar approximants are discussed and DLog additive recursive approximants are introduced as their generalization. They are applied to the problem of interpolation. Several examples of interpolation are considered.

Tauc-plot scale and extrapolation effect on bandgap estimation from UV–vis–NIR data – A case study of β-Ga2O3

The effect of the Tauc plot scale and bandgap extrapolation technique on estimated optical bandgap values is often not strongly emphasized. Herein, we demonstrate that the scale of the conventional Tauc plot and the extrapolation technique poses significant influence on the determined value of bandgap. The nanomaterial used for this study was prepared by the CVD method using different H2 reducing gas flow rates. XRD measurements confirmed polycrystalline β-Ga2O3 with high crystalline quality. FE-SEM analysis revealed nanohump-like morphology. UV–vis–NIR measurements generally showed increasing bandgap with rising H2 supply into the horizontal reactor. Specifically, it was observed that the proper extrapolation technique for bandgap estimation is more appropriate as compared to the values obtained from the traditional direct extrapolation method. It is established that direct extrapolation technique has the potential to either under - or over-estimate bandgap values, whereas the proper extrapolation method is promising for more reasonable values of optical energy gap.

Anaerobic co-digestion of rabbit manure and sorghum crops in a bench-scale biodigester

Any type of biomass can be used as substrate for biogas production, but the performance of the biodigestion depends on the composition of the feed, and no direct extrapolation of the yield of the process from one substrate to another can be made. In this work, the performance of a bench-scale anaerobic biodigester of 93 L installed at ambient conditions is studied. The biodigester was set up in a region where temperature varies significantly during the year, and was operated under semi-batch conditions with non-thermal control for 16 months with a feed of rabbit manure and ground sorghum grains. To our knowledge, this is the first time the co-digestion of rabbit manure with sorghum grains is considered. To evaluate the biodigestion performance, critical operational variables (pH, temperature, biogas flowrate) were monitored, and composition of substrate, digestate and produced biogas was determined. Moreover, the following variables were quantified: (a) the theoretical methane potential, (b) the specific methane yield and (c) the degree of degradation of the substrate. A 1-D non-stationary model was formulated and validated with experimental data in order to analyze, in a theoretical form, the impact of incorporating thermal insulation to the unit. The results show that is it possible to produce biogas in a bench-scale biodigester, with a novel feed of rabbit manure and ground sorghum grains, in a region with significant temperature changes along the year. Moreover, it is shown that the 1-D model constitutes a useful tool for the design or improvement of biodigesters regarding the insulation system and the warming policies.

Deep-sea eruptions boosted by induced fuel–coolant explosions

The majority of Earth's volcanic eruptions occur beneath the sea, but the limited number of direct observations and samples limits our understanding of these unseen events. Subaerial eruptions lend some insight, but direct extrapolation from the subaerial to the deep sea is precluded by the great differences in pressure, thermal conditions, density and rheology, and the interplay among them. Here we present laboratory fragmentation experiments that mimic deep-sea explosive eruptions and compare our laboratory observations with those from the kilometre-deep submarine eruption of Havre Volcano, Kermadec Arc, New Zealand, in 2012. We find that the Havre eruption involved explosive fragmentation of magma by a pressure-insensitive interaction between cool water and hot magma, termed an induced fuel-coolant interaction. The laboratory experiments show that this water-magma interaction is initiated by the formation of cracks in cooling magma into which the water coolant can infiltrate, driving explosive fragmentation. Explosive submarine eruptions have previously been considered unlikely because stabilization of a vapour film at the magma-water contact was thought to be a key requirement but is suppressed at depths exceeding 100 m. However, here we demonstrate that these induced fuel-coolant interactions between magma and water can occur in a range of wet environments regardless of pressure, from the subaerial to the deep sea, and may operate on different planets, as well as apply to materials other than magma and water.

A proposed pediatric biopharmaceutical classification system for medications for chronic diseases in children

Age-appropriate pediatric formulations for oral administration can be challenging to formulate. Development of such formulations is often time consuming, labor-intensive and costly. The Biopharmaceutical Classification System (BCS), developed more than two decades ago, is used to develop suitable oral drug formulations for adult use. In theory, some of the same principles could be applied to formulate pediatric oral liquid dosage forms. However, the present BCS system was developed using adult gastrointestinal physiologic factors. Direct extrapolation of this method to develop pediatric oral dosage forms is inappropriate due to differences in adult and pediatric gastrointestinal physiologic differences during development. To date age-appropriate BCS to guide pediatric oral liquid formulation development has not been developed for various pediatric subpopulations.The objective of this study was to provisionally classify oral liquid formulations of extemporaneously prepared drugs at our institution into an age-appropriate BCS class after elimination of any duplicate listing when matched with the most current World Health Organization's Essential Medicines List for Children available at the time of this study and other published studies that may have reported BCS classification of drugs used as extemporaneous oral liquid formulations in children to treat chronic or rare diseases. A total of 96 orally administered extemporaneously compounded liquid formulations were included in this classification. Dose numbers were calculated using age-appropriate initial gastric volume for neonates, 6-month-old infants, and children up to 6 years of age. Using age-appropriate initial gastric volumes and pediatric and neonatal Lexicomp® age-specific maximal dosing recommendations for calculation of dose numbers, the solubility classes shifted for 62.5% of the drugs studied. A significant number of currently used extemporaneously compounded oral liquid formulations for age groups of children included in this study may not provide formulations with predictable safety and efficacy. Factors used in development of adult BCS cannot be applied directly to pediatric subpopulations.

Comparison Simulation Analysis of the Gradual Summation of a Function with Recognition of Direct Extrapolation Via IN Series

A set of data pattern that have the characteristic of a function can be approached using Newton series simulation. When using the Newton series, the simulation result of the summation of extrapolation data can be gradually done in step by step. However, if using the IN series, the simulation result of the summation of extrapolation data doesn’t need to be gradually done in step by step. The methodology in this research compares the data pattern from the simulation results of the high degree function with the results of interpolation and extrapolation from the results of the IN series simulation. Futhermore, will be carried out comparison simulation analysis of the summation of the function values gradually with the extrapolation function directly using the IN series. The result of comparison simulation analysis point out that the value of the total summation of data between the gradual and the direct summation is the same, so that the direct sum technique using the IN Series is able to make the total sum process more efficient.