Sampling Duration Research Articles

TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research.

The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms’ performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.

Serum Calcification Propensity in Children on Chronic Hemodialysis

Serum Calcification Propensity in Children on Chronic Hemodialysis

Current clinical methods of measurement of respiratory rate give imprecise values.

BackgroundRespiratory rate is a basic clinical measurement used for illness assessment. Errors in measuring respiratory rate are attributed to observer and equipment problems. Previous studies commonly report rate differences ranging from 2 to 6 breaths·min−1 between observers.MethodsTo study why repeated observations should vary so much, we conducted a virtual experiment, using continuous recordings of breathing from acutely ill patients. These records allowed each breathing cycle to be precisely timed. We made repeated random measures of respiratory rate using different sample durations of 30, 60 and 120 s. We express the variation in these repeated rate measurements for the different sample durations as the interquartile range of the values obtained for each subject. We predicted what values would be found if a single measure, taken from any patient, were repeated and inspected boundary values of 12, 20 or 25 breaths·min−1, used by the UK National Early Warning Score, for possible mis-scoring.ResultsWhen the sample duration was nominally 30 s, the mean interquartile range of repeated estimates was 3.4 breaths·min−1. For the 60 s samples, the mean interquartile range was 3 breaths·min−1, and for the 120 s samples it was 2.5 breaths·min−1. Thus, repeat clinical counts of respiratory rate often differ by >3 breaths·min−1. For 30 s samples, up to 40% of National Early Warning Scores could be misclassified.ConclusionsEarly warning scores will be unreliable when short sample durations are used to measure respiratory rate. Precision improves with longer sample duration, but this may be impractical unless better measurement methods are used.

Hierarchical multiscale numerical modelling of internal erosion with discrete and finite elements

This paper presents a coupled finite and discrete-element model (FEM and DEM) to simulate internal erosion. The model is based on ICY, an interface between COMSOL, an FEM engine, and YADE, a DEM code. With this model, smaller DEM subdomains are generated to simulate particle displacements at the grain scale. Particles in these small subdomains are subjected to buoyancy, gravity, drag and contact forces for short time steps (0.1 s). The DEM subdomains provide the macroscale (continuum) model with a particle flux distribution. Through a mass conservation equation, the flux distribution allows changes in porosity, hydraulic conductivity and hydraulic gradient to be evaluated for the same time steps at a larger, continuum scale. The updated hydraulic gradients from the continuum model provide the DEM subdomains with updated hydrodynamic forces based on a coarse-grid method. The number of particles in the DEM subdomains is also updated based on the new porosity distribution. The hierarchical multiscale model (HMM) was validated with the simulation of suffusion. Results for the proposed HMM algorithm are consistent with results based on a DEM model incorporating the full sample and simulation duration. The proposed HMM algorithm could enable the modelling of internal erosion for soil volumes that are too large to be modelled with a single DEM subdomain.

Estimating Mean Bedload Transport Rates and Their Uncertainty

Measuring bedload transport rates usually involves measuring the flux of sediment or collecting sediment during a certain interval of time Δt. Because bedload transport rates exhibit significant non‐Gaussian fluctuations, their time‐averaged rates depend a great deal on Δt. We begin by exploring this issue theoretically within the framework of Markov processes. We define the bedload transport rate either as the particle flux through a control surface or as a quantity related to the number of moving particles and their velocities in a control volume. These quantities are double averaged; that is, we calculate their ensemble and time averages. Both definitions lead to the same expression for the double‐averaged mean rate and to the same scaling for the variance's dependence on the length of the sampling duration Δt. These findings lead us to propose a protocol for measuring double‐averaged transport rates. We apply this protocol to an experiment we ran in a narrow flume using steady‐state conditions (constant water discharge and sediment feed rates), in which the time variations in the particle flux, the number of moving particles, and their velocities were measured using high‐speed cameras. The data agree well with the previously defined theoretical relationships. Lastly, we apply our experimental protocol to other flow conditions (a long laboratory flume and a gravel‐bed river) to show its potential across various contexts.

Quantitative biomonitoring of polycyclic aromatic compounds (PACs) using the Sydney rock oyster (Saccostrea glomerata)

Increasing our understanding of the bioavailable fractions of polycyclic aromatic compounds (PACs) in an aquatic environment is important for the assessment of the environmental and human health risks posed by PACs. More importantly, the behaviour of polar polycyclic aromatic hydrocarbons (polar PAHs), which are metabolites of legacy PAHs, are yet to be understood. We, therefore, carried out a study involving Sydney rock oysters (Saccostrea glomerata) sourced from two locations, that had been exposed to PAH contamination, within an Australian south-east estuary. Biomonitoring of these oysters, following relocation from the estuary to a relatively isolated waterway, was done at 24 and 72 h after deployment and subsequently at 7, 14, 28, 52 and 86 days. Control samples from Camden Haven River were sampled for PAC analyses just before deployment, after 28 days and at the end of the study (day 86). Lipid-normalised concentrations in oyster tissues across the 86-day sampling duration, elimination rate constants (k2), biological half-lives (t1/2) and time required to reach 95% of steady-state (t95) were reported for parent PAHs and the less-monitored polar PAHs including nitrated/oxygenated/heterocyclic PAHs (NPAHs, oxyPAHs and HPAHs) for the three differently sourced oyster types. Most of the depurating PAHs and NPAHs, as well as 9-FLO (oxyPAH), had k2 values significantly different from zero (p < 0.05). All other oxyPAHs and HPAHs showed no clear depuration, with their concentrations remaining similar. The non-depuration of polar PAHs from oyster tissues could imply greater human health risk compared to their parent analogues.

In-vitro and In-vivo Evaluation of Anti-trypanosomal Activity of Carica papaya Seed Extracts and Fractions in Albino Wister Rats

Aims: This study presents baseline data on the In-vitro and In-vivo evaluation of anti-trypanosomal activity of Carica papaya seed extracts and fractions in Albino Wister rats.&#x0D; Study Design: Mention the design of the study here.&#x0D; Place and Duration of Study Sample: Department of Biochemistry, Modibbo Adama University of Technology, Yola, between June 2009 and July 2010.&#x0D; Methodology: 56 Wister rats of both sexes were randomly divided into 8 groups (I – VIII) of 7 rats each were used for this study. Four concentrations (100, 200, 400 and 800 mg/kg) of different extracts of seed carica papaya were screened for trypanocidal activity against Trypanosoma brucei In vitro and In vivo. The effect of the extracts was evaluated for trypanocidal activity in rats infected and not infected with the parasite. Administration of the extract and the drugs was orally daily for 5 consecutive days from day 7 of post infection. Level of parasitemia and body weight was taken daily for 21 days.&#x0D; Results: The extracts inhibited parasite motility and totally eliminated the organisms at the concentrations used In vitro. The extract also showed promising in vivo trypanocidal activity. The observed In vitro and In vivo trypanocidal activities may be due to the presence of bioactive compounds present in the extracts as seen in this study. The extract also improved the observed decreases in haematological parameters of the treated rats, which may be due to their ability to decrease parasite load. The LD50 was estimated to be ≥2,000 mg/Kg (v/v) for acute oral toxicity test (because all the rats survived at the end of the 14-day observation period). This is an indication of very low toxicity, implying that the extract could be administered with some degree of safety. A significant decreased (p&lt;0.05) were observed in weight of rats at 100 mg/kg, 200 mg/kg 400 mg/kg 800 mg/kg negative control and prophylactic at four to eight days of infections, while significantly increased (p&lt;0.05) were observed in weight of rats for berenil control and normal control.&#x0D; Conclusion: The decrease in weight of rats could be as a result of loss of appetite due to severe fever and also the trypanosome.

Applying Generalizability Theory to Optimize Analysis of Spontaneous Teacher Talk in Elementary Classrooms.

Purpose Although sampling teachers' child-directed speech in school settings is needed to understand the influence of linguistic input on child outcomes, empirical guidance for measurement procedures needed to obtain representative samples is lacking. To optimize resources needed to transcribe, code, and analyze classroom samples, this exploratory study assessed the minimum number and duration of samples needed for a reliable analysis of conventional and researcher-developed measures of teacher talk in elementary classrooms. Method This study applied fully crossed, Person (teacher) × Session (samples obtained on 3 separate occasions) generalizability studies to analyze an extant data set of three 10-min language samples provided by 28 general and special education teachers recorded during large-group instruction across the school year. Subsequently, a series of decision studies estimated of the number and duration of sessions needed to obtain the criterion g coefficient (g > .70). Results The most stable variables were total number of words and mazes, requiring only a single 10-min sample, two 6-min samples, or three 3-min samples to reach criterion. No measured variables related to content or complexity were adequately stable regardless of number and duration of samples. Conclusions Generalizability studies confirmed that a large proportion of variance was attributable to individuals rather than the sampling occasion when analyzing the amount and fluency of spontaneous teacher talk. In general, conventionally reported outcomes were more stable than researcher-developed codes, which suggests some categories of teacher talk are more context dependent than others and thus require more intensive data collection to measure reliably.

Analysis of acoustic Doppler current profiler mean velocity measurements in shallow flows

Acoustic Doppler current profilers (ADCPs) are commonly used instruments for measurement of natural streamflow and flow in manmade channels. Velocities measured in a profile by the instrument are used to estimate the discharge in a channel. A Teledyne RD Instruments StreamPro ADCP was used to measure the mean velocity simultaneously with a laser Doppler anemometer (LDA) in a laboratory flume. An average of 3.9% under-prediction of the mean velocity measured by the ADCP occurred when compared to the measurements of the LDA. Moreover, this study shows that the sampling duration of the measurements significantly impacts the mean point velocities measured by up to 50%.

Fine Surface Structures Influencing on Liquid Quenching*

Abstract Instead of quenching medium, quenching equipment and quenching parameters, an adapted surface structure of the heat treated component shall be investigated as influencing factor on rewetting during liquid quenching. Steel cylinders and aluminium cylinders have been quenched in water baths and oil baths. Fine surface structures by machining with turning tools with small flange radii have caused a significant relative surface increase compared to flat samples and thereby a significant decrease in rewetting duration of the whole sample (from rewetting start to finish). This is beneficial regarding quenching homogeneity. Local surface structures applied by ultrashort laser pulses have also influenced on rewetting, if resulting fins are arranged in axial cylinder direction and possess a sufficient axial length.

The ‘decoada’ phenomenon effect on the Paraguay river water quality, Northern Pantanal

In the Pantanal, during the beginning of the flooding hydrological phase occurs a natural phenomenon called 'decoada'. Characterized by the water quality alteration of the rivers, in floodplain areas and marginal lagoons, with the possibility of significant fish mortality, depending on the changes’ magnitude. For this purpose, throughout a hydrological cycle (July 2018 to June 2019), precipitation, bathymetry and water quality were monitored monthly, in 6 sampling points, to determine, the moment, duration and intensity of the decoada, and its effects on water quality in the Paraguay River, northern Pantanal, near the municipality of Cáceres/MT. The dissolved oxygen (DO) concentration was used as an indicator, in which DO &lt; 3.0 mg/L, during the flood season, was considered indicative of the potential event occurrence. According to the records, there were different hydrological periods, where the flooding and high waters presented DO values lower than in the dry and ebb phases, with a drastic change from October 2018 (DO = 6.37 ± 0.17 mg/L) to November 2018 (DO = 2.78 ± 0.05 mg/L), registering, therefore, in all points, low-intensity decoada. The DO values remained below 5 mg/L, the maximum limit allowed by CONAMA Resolution 357/2005 for class II rivers. From November 2018 to April 2019 in all sampling points, the minimum value was recorded in March 2019 in the bay, with DO = 1.84 mg/L, considered a medium level decoada. The principal component analysis (PCA), proved the results difference of decoada found in the river and the bay, presented with greater intensity and duration in the bay. The parameters that influenced the decoada, according to the PCA, were pH, temperature, precipitation, turbidity and DO.

Intestinal permeability in participants with thermal injury: A case series from a prospective, longitudinal study (HESTIA)

ObjectivesSevere thermal injury (TI) has been associated with increased intestinal permeability and the development of multiple organ dysfunction syndrome. The aim of this case series from a prospective, longitudinal study is to describe the impact of TI on intestinal permeability in critically ill participants with TI versus observations from healthy participants. MethodsParticipants with TI ≥ 15% total body surface area and healthy participants were recruited into the study. The co-primary endpoints were lactulose/mannitol [L/M] ratio (a) within 24 h of hospital admission and (b) over time. Exploratory endpoints included fractional excretion of sucralose and changes in blood biomarkers (eg, occludin and soluble CD14 [sCD14]). Clinical severity of injury, demographic and morbidity data were also collected. ResultsFourteen healthy participants and three participants with TI were enrolled. Case histories for two of the three participants with TI showed peak L/M-measured permeability ~10-fold higher than healthy participants, with a clear pattern between degree and timing of injury and increases in permeability. Serum occludin and sCD14 levels were elevated in all three participants with TI versus healthy participants. The study was terminated early with a reduced sample size and duration than planned. ConclusionObserved changes in L/M-measured permeability of participants with TI support the existing literature of raised intestinal permeability in critically ill individuals, with increases seen in the first few days of hospital admission. Occludin and sCD14 are identified as potential surrogate markers of raised permeability but require validation in larger studies.

Functional connectivity of EEG is subject-specific, associated with phenotype, and different from fMRI

A variety of psychiatric, behavioral and cognitive phenotypes have been linked to brain ‘’functional connectivity’’ -- the pattern of correlation observed between different brain regions. Most commonly assessed using functional magnetic resonance imaging (fMRI), here, we investigate the connectivity-phenotype associations with functional connectivity measured with electroencephalography (EEG), using phase-coupling. We analyzed data from the publicly available Healthy Brain Network Biobank. This database compiles a growing sample of children and adolescents, currently encompassing 1657 individuals. Among a variety of assessment instruments we focus on ten phenotypic and additional demographic measures that capture most of the variance in this sample. The largest effect sizes are found for age and sex for both fMRI and EEG. We replicate previous findings of an association of Intelligence Quotient (IQ) and Attention Deficit Hyperactivity Disorder (ADHD) with the pattern of fMRI functional connectivity. We also find an association with socioeconomic status, anxiety and the Child Behavior Checklist Score. For EEG we find a significant connectivity-phenotype relationship with IQ. The actual spatial patterns of functional connectivity are quite different between fMRI and source-space EEG. However, within EEG we observe clusters of functional connectivity that are consistent across frequency bands. Additionally we analyzed reproducibility of functional connectivity. We compare connectivity obtained with different tasks, including resting state, a video and a visual flicker task. For both EEG and fMRI the variation between tasks was smaller than the variability observed between subjects. We also found an increase of reliability with increasing frequency of the EEG, and increased sampling duration. We conclude that, while the patterns of functional connectivity are distinct between fMRI and phase-coupling of EEG, they are nonetheless similar in their robustness to the task, and similar in that idiosyncratic patterns of connectivity predict individual phenotypes.

Prevalence and significance of clonal hematopoiesis of indeterminate prognosis (CHIP) in multiple myeloma.

8542 Background: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence of leukemia-associated somatic mutations in clonally expanded hematopoietic stem cells with a VAF of ≥2%. CHIP has been associated with myeloid malignancies and increased all cause mortality largely from atherovascular disease. The prevalence and impact of CHIP in patients with myeloma (MM) is yet to be defined. Aims: Evaluate the prevalence and significance of CHIP in 101 lenalidomide exposed patients with multiple myeloma. Methods: 101 MM patients, the majority exposed to &gt; 2 years of lenalidomide (Len), with stored mononuclear blood samples were identified for Next Generation Sequencing (NGS) using a panel encompassing 42 gene mutations associated with CHIP. Electronic medical records were reviewed and outcomes of secondary malignancy, macrocytosis, thrombosis and mortality were extracted. Results: Thirty of 101patients were found to have CHIP with the most frequent mutations: DNMT3A (12%), TET2 (5%), and TP53 (4%). One third of patients with CHIP had &gt; 1 mutation (37%). At 68 months median follow up over a quarter of patients experienced thrombosis (31%) and 13% developed subsequent malignancy/premalignant condition including myelodysplastic syndrome (3%). There was no significant difference in age, gender, duration of Len prior to NGS testing, thrombosis complication, or survival in those with versus without a CHIP mutation. At last F/U 30% had died, 25% remained on therapy, 27% were on maintenance therapy and 11% were on observation alone. Conclusions: CHIP mutations are common in plasma cell neoplasms, with 30% of patients in this study retrospectively found to have CHIP mutations by NGS testing. CHIP mutations have been associated with cardiovascular events and malignancy development, however no associations were identified in this small study. Limitations to this study include small sample size, retrospective nature and duration of follow up. Further study of this very common finding in MM patients regarding timing of development and subsequent impact of these mutations could help risk stratify and inform therapy selection. [Table: see text]

Assessing the influence of vegetation structure and phenological variability on pollen‐vegetation relationships using a 15‐year Neotropical pollen rain record

AbstractQuestionsPollen collected from aerial pollen traps are used to interpret compositional changes in the fossil pollen record. Relationships between pollen abundances and vegetation are commonly measured using the ratio between the abundance of a pollen type and its corresponding basal area in a plant community (R‐rel). Pollen–vegetation relationships have been extensively studied in temperate and boreal latitudes using surface sediment, moss polster and pollen trap samples, representing long‐term accumulations of pollen. In contrast, pollen–vegetation relationships are not well‐resolved in diverse tropical habitats because of a lack of modern long‐term pollen and vegetation datasets. In the present study, we address two primary questions: 1. How variable are tropical pollen–vegetation relationships measured using R‐rel over time? 2. To what extent are differences in pollen abundances among traps related to variability in basal area in the surrounding community?LocationBarro Colorado Island, Panama.MethodsVariability in an annually sampled, 15‐year pollen rain was compared with annual basal area data collected over the same timeframe using R‐rel.ResultsR‐rel values were highly variable on a year‐to‐year basis and more consistent over time‐averaged sampling windows ≥3 years. A strong positive relationship between pollen abundances and local basal area surrounding pollen traps was determined in eight taxa.ConclusionsThe pollen–vegetation relationships provide a summary of the pollen representation of Neotropical taxa common in paleoecological samples over an extended sampling duration that approaches the timespan represented in lake sediment samples (~20 years). The results highlight taxa in which differences in pollen abundances among traps were strongly correlated with changes in surrounding basal area.

Injuries related to animal sacrifice during the Feast of Sacrifice in Turkey

ABSTRACTBACKGROUND: The Feast of Sacrifice is a significant annual religious festival in Muslim countries. In these festivals, thousands of animals are usually sacrificed by inexperienced individuals. Thus, many injuries occur during sacrificing of animals.OBJECTIVES: Describe injuries related to animal sacrifice or meat processing.DESIGN: Cross-sectional descriptive study.SETTINGS: Three hospitals in different cities of Turkey.SUBJECTS AND METHODS: Severity and type of injuries that occur during animal sacrifice or meat processing after the sacrifice and hospital costs.MAIN OUTCOME MEASURES: Identification and classification of sacrifice related injuries.SAMPLE SIZE: 301 injured individuals.RESULTS: The mean age of the patients was 42.5 (14.8) years and 83.1% of the subjects were male. Most (90.0%) injuries were penetrating injuries and 10.0% were blunt traumas. Upper and lower extremity injuries were identified in 77.4% and 17.9% of cases, respectively. Almost half of the injuries were on the left hand (49.8%). Almost all (96.6%) cases were treated and discharged from emergency services. Median hospital cost per patient was 103.14 Turkish Liras (35.95-852.66 Turkish Liras) (19.53 USD [6.80-161.48 USD]).CONCLUSIONS: Even though injuries related to animal sacrifice are usually caused by minor sharp objects, they can be severe and life threatening on rare occasions. To minimize the injuries that may occur during this period, public education and more convenient sacrifice centers may be helpful.LIMITATIONS: Small sample, single country, and short duration of the study.CONFLICT OF INTEREST: None.

Nutrition-related outcomes and dietary intake in non–mechanically ventilated critically ill adult patients: A pilot observational descriptive study

BackgroundCritically ill patients who do not receive invasive mechanical ventilation (IMV) are a growing population, experiencing complex interventions that may impair dietary intake and nutrition-related outcomes. ObjectivesThe objectives of this study were to quantify intake and nutrition-related outcomes of non-IMV critically ill patients and to establish feasibility of methods to measure nutrition-related outcomes in this population. MethodsNon-IMV adult patients expected to remain in the intensive care unit (ICU) for ≥24 h were eligible. Nutrition-related outcomes were assessed at baseline by subjective global assessment (SGA); on alternate study days by mid-upper arm circumference (MUAC), calf circumference (CC), and ultrasound of quadriceps muscle layer thickness (QMLT); and daily by body weight and bioelectrical impedance analysis (BIA). Data were censored at day 5 or ICU discharge. Dietary intake from all sources, including oral intake via investigator-led weighed food records, was quantified on days 1–3. Feasibility was defined as data completion rate ≥70%. Data are expressed as mean (standard deviation) or median [interquartile range (IQR)]. ResultsTwenty-three patients consented (50% male; 53 [42–64] y; ICU stay: 2.8 [1.9–4.0] d). Nutrition-related outcomes at baseline and ICU discharge were as follows: MUAC: 33.2 (8.6) cm (n = 18) and 29.3 (5.4) cm (n = 6); CC: 39.5 (7.4) cm (n = 16) and 37.5 (6.2) cm (n = 6); body weight: 95.3 (34.8) kg (n = 19) and 95.6 (41.0) kg (n = 10); and QMLT: 2.6 (0.8) cm (n = 15) and 2.5 (0.3) cm (n = 5), respectively. Oral intake provided 3155 [1942–5580] kJ and 32 [20–53] g protein, with poor appetite identified as a major barrier. MUAC, CC, QMLT, and SGA were feasible, while BIA and body weight were not. ConclusionsOral intake in critically ill patients not requiring IMV is below estimated requirements, largely because of poor appetite. The small sample and short study duration were not sufficient to quantify changes in nutrition-related outcomes. MUAC, CC, QMLT, and SGA are feasible methods to assess nutrition-related outcomes at a single time point in this population.

Effects of Fundamental Frequency, Vocal Intensity, Sample Duration, and Vowel Context in Cepstral and Spectral Measures of Dysphonic Voices.

Purpose Smoothed cepstral peak prominence (CPPS) and harmonics-to-noise ratio (HNR) are acoustic measures related to the periodicity, harmonicity, and noise components of an acoustic signal. To date, there is little evidence about the advantages of CPPS over HNR in voice diagnostics. Recent studies indicate that voice fundamental frequency (F0) and intensity (sound pressure level [SPL]), sample duration (DUR), vowel context (speech vs. sustained phonation), and syllable stress (SS) may influence CPPS and HNR results. The scope of this work was to investigate the effects of voice F0 and SPL, DUR, SS, and token on CPPS and HNR in dysphonic voices. Method In this retrospective study, 27 Brazilian Portuguese speakers with voice disorders were investigated. Recordings of sustained vowels (SVs) /a:/ and manually extracted vowels (EVs) /a/ from Consensus Auditory-Perceptual Evaluation of Voice sentences were acoustically analyzed with the Praat program. Results There was a highly significant effect of F0, SPL, and DUR on both CPPS and HNR (p < .001), whereas SS and vowel context significantly affected CPPS only (p < .05). Higher SPL, F0, and lower DUR were related to higher CPPS and HNR. SVs moderately-to-highly correlated with EVs for CPPS, whereas HNR had few and moderate correlations. In addition, CPPS and HNR highly correlated in SVs and seven EVs (p < .05). Conclusion Speaking prosodic variations of F0, SPL, and DUR influenced both CPPS and HNR measures and led to acoustic differences between sustained and excised vowels, especially in CPPS. Vowel context, prosodic factors, and token type should be controlled for in clinical acoustic voice assessment.

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion.

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration-time curve of vitamin K1 was fit to a linear equation following PCSII (R2 =0.9599±0.0096). Then, half-time (T1/2 ), apparent volume of distribution (Vd ), and clearance rate (CL) were estimated successively. T1/2 of vitamin K1 was 4.07±0.41hour, CL was 89.47±3.60mL/h, and Vd was 525.38±54.45mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T1/2 and mean residence time (MRTINF ) for a sampling duration of 6h were shorter than those of 12 hours or 24hours sampling duration following IV (P<.05, P<.01). In addition, T1/2 of vitamin K1 was obviously different from MRT-equated half-time (T1/2,MRT )(P<.05). Vd and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P<.01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration-time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T1/2 and a relatively large Vd following PCSII.

Realistic Mathematics Education in Indonesia and Recommendations for Future Implementation: A Meta-Analysis Study

This meta-analysis study aims to investigate the effectiveness of applying realistic mathematics education (RME) in Indonesia to students' mathematical abilities. This study analyzes 95 effect sizes from 72 studies that have been published in national and international journals or proceedings from 2010 to 2019. Comprehensive Meta-Analysis (CMA) software is used to aid analysis. As a result of the study, the overall effect size was 1.104, with a standard error of 0.065 according to the random-effects model. These results indicate that the average person who is ranked 13th in the experimental group is equivalent to those who are ranked 4th in the control group. This research was carried out by considering four characteristics, resulting in significant differences in terms of sample size and duration of treatment. Thus the application of RME in Indonesia is very effective in improving students' mathematical abilities by considering the sample size and duration of treatment.