Sort. (AUC), and both toxicity . How to calculate pharmacokinetic parameters? The dose proportionality of carvedilol over the dose range 8-128 mg was assessed by fitting a power model. The half-life (t 1 / 2) is the time it takes for the plasma concentration of a drug or the amount of drug in the body to be reduced by 50%. The Peak/MIC ratio is simply the Cpmax divided by the MIC. The total area is 1/2 - FPR/2 + TPR/2 . The half-life will remain constant, irrespective of how high the concentration. How do you calculate t1 2 of a drug? liver or kidney). The time following drug administration at which the peak concentration of Cmax occurs, tp (for any route of administration but the intravenous), is given by tp = (ln ka - ln kel )/ (ka - kel). Use the advanced version if you wish to manipulate this value. 2011. Css(ave) = Average drug concentration at steady state. AUC = Area under the concentration-time curve F = bioavailability The term absolute bioavailability is used when the fraction of absorbed drug is related to its i.v. The definition of elimination half-life is the length of time required for the concentration of a particular substance (typically a drug) to decrease to half of its starting dose in the body. Five pharmacokinetic parameters that are important in therapeutic drug monitoring include: Bioavailability. actual body weight for calculating the CRCL. The absorption rate constant Ka is a value used in pharmacokinetics to describe the rate at which a drug enters into the system. Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is an online calculator to find the dosage of. Linear Pharmacokinetics ,the characteristic of drugs that indicates the instantaneous rate of change in drug concentration depends only on the current concentration. Route of administration. How do you calculate pharmacokinetics? What is the ICD-10-CM code for skin rash? Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet. Description. See the drug models section of this help file for further information. The Wagner-Nelson method estimates the fraction of drug absorbed over time, relative to the total amount to be absorbed, following the method described in Gibaldi and Perrier (1975) pages 130 to 133. Pharmacodynamic phase. This can be calculated using the following equation: If the % extrapolated is greater than 20%, than the total AUC may be unreliable. The primary pharmacokinetic disposition parameter is clearance. The half-life (t1/2) is the time it takes for the plasma concentration of a drug or the amount of drug in the body to be reduced by 50%. Calculate the AUC of the resampled data. (Remember that ln is the natural logarithm, to the base e, rather than the common logarithm or logarithm to the base 10; ln X=2.303 log X.). For example, in 2010 there were 1,154 homicides cleared and 1,809 homicides reported. Drug needs to be given at 20 mg/h. Our experts have done a research to get accurate and detailed answers for you. , (2,000 / 600) = 0.05/ KE = 0.015 hr (-) . What to say when apologising to your boyfriend? From this bootstrap distribution, calculate the mean AUC and the desired percentile confidence interval. Calculation of first segment The first segment can be calculated after determining the zero plasma concentration Cp0 by extrapolation AUC0-1 = Cp0+ Cp1 . The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)]. Abstract. read more (including receptor sensitivity), postreceptor effects, and chemical interactions. This equals a homicide clearance rate of 63.8 percent. read more , ie, the drug's effects. This is closely related to but distinctly different from pharmacodynamics, which examines the drug's effect on the body more closely. It is a standard measurement in pharmacokinetics. The half-life is thus the most important parameter for deciding on a dosing regime. Most used only a small number of pharmacokinetic curves, studied a 12-h AUC and not a 4-h AUC, or did not validate their equations in a population different to the one used in developing the AUC equation. AUC is approximated by a series of trapezoids. Integrating the PK parameters with the MIC gives us three PK/PD parameters which quantify the activity of an antibiotic: the Peak/MIC ratio, the T>MIC, and the 24h-AUC/MIC ratio. This is how you can get it, having just 2 points. As an example, calculate the following loading dose (Mass(mg)/Time(h)): Clearance = 2 L/h. As we cannot get the assays to go to infinity, we have to extrapolate to infinity. Concept of Clearance The clearance of substance x (Cx) can be calculated as Cx = Ax /Px, where Ax is the amount of x eliminated from the plasma, Px is the average plasma concentration, and Cx is expressed in units of volume per time. Target concentration = 5 mg/L. dosing via AUC. AUC is an important parameter in pharmacokinetic studies. Equation 1: Vd = total amount of drug in the body plasma drug concentration. Step 1. Which of the following will be the pharmacokinetic application of prodrugs? down="Linear" means linear trapezoidal rule with linear interpolation. Rowland M, Tozer TN. View source: R/nca.R. A A clearance rate is calculated by dividing the number of crimes cleared by the number of crimes reported; the result is multiplied by 100. The amount eliminated by the body (mass) = clearance (volume/time) * AUC (mass*time/volume). Planimeter Method. Drugs given by intravenous route have 100% bioavailability. The last piece (t 1 - t 2) is the duration of time. Repeat steps 1 and 2 many times until the distribution of AUC values converges. At steady state, the amount of drug administered on each dosing occasion is matched by an equivalent amount of drug leaving the body between each dose. We are giving drug every 12 hours. The same is true of alcohol, which can potentiate the sedative effects of many drugs. CrCl for male = [ (140 - age) * Weight in kilograms * 1.23] / (Serum Creatinine in mol/L) CrCl for female = [ (140 - age) * Weight in kilograms * 1.04] / (Serum Creatinine in mol/L) The calculation of the ideal body weight by Devine's formula: Male = 50 kg + (2.3 * (Height in inches - 60)) Female = 45.5 kg + (2.3 * (Height in inches - 60)) Figure 3 shows that half-life is in fact a derived pharmacokinetic parameter. Counting Square Method.Chapters:0:00 - intro0:16 - Area Under the Curve(AUC)0:51 - Applications of Area Under the Curve(AUC)2:11 - Methods to Determine Area Under the Curve(AUC)3:00 - Trapezoidal Rulearea under the curve, calculate auc trapezoidal rule, area under curve auc, trapezoidal rule, calculation of auc, calculation of auc by trapezoidal rule, pharmacokinetics AUC, log-linear trapezoidal rule, biopharmaceutics and pharmacokinetics, biopharmaceutics and pharmacokinetics lecture, biopharmaceutics lecture, pharmacyd, area under the curve auc calculation, how to calculate auc, pharmacyd by asim More video from PharmacyD : Covid-19 Vaccine Side Effects: https://youtu.be/7bz9OZIDuP8 Cardiac Arrest vs Heart Attack: https://youtu.be/a_xdDCTK25s Liver Function Tests (LFTs): https://youtu.be/GZOu2tnt6D0 High Blood Pressure in Pregnancy: https://youtu.be/esZownfMXgo Thalassemia (A Genetic Blood Disorder): https://youtu.be/0iB-fP0wcD4 Biopharmaceutics \u0026 Pharmacokinetics: https://youtube.com/playlist?list=PLnn3dWigwUyYxkU0JqIW1PfTMrHdb4UQJDon't click this link: https://bit.ly/3vfeMa4 Facebook: https://web.facebook.com/pharmacyd0929For any Queries and Suggestions Email on: pharmacyd0929@gmail.comDisclaimer:\"Content is For Education Purpose Only, Creamed From Various Authentic Books of Pharmacy \u0026 Medicine.\"A Famous Quote is: \"What We Know is a Drop. To hand calculate the AUC using first order equations, the Sawchuk-Zaske method can be used. This is in contrast to parameters like bioavailability and elimination half-life, which can often be found in drug and pharmacology handbooks. Differential equations are used to relate the concentrations of drugs in various body organs over time. A model that has an AUC of 1 is able to perfectly classify observations into classes while a model that has an AUC of 0.5 does no better than a model that performs random guessing. Steady state means that the rate of the drug entering the body equals the rate of the drug leaving the body (rate in = rate out). Think of pharmacokinetics as a drug's journey through the body, during which it passes through four different phases: absorption, distribution, metabolism, and excretion (ADME). Whenever the AUC equals 1 then it is the ideal situation for a . Parameter names are fixed and cannot be changed. AUC(0-inf): AUC curve to infinite time. This can be calculated from the AUC(0-t) by the addition of a Return a table of cumulative values. Equation 2: F = mass of the drug delivered to the plasma total mass of the drug administered. After an iv bolus injection, the AUC can be calculated by the following equation: AU C = C (0) A U C = C ( 0) Trapezoidal rule: It consists in dividing the plasma concentration-time profile into several trapezoids and calculating the AUC by adding the area of these trapezoids. Without having the corresponding IV data you will not be able to calculate CL, Vd, elimination rate constant, absorption rate constant, bioavailability, or really any parameters other than the. (M1.PH.15.75) A pharmaceutical company is attempting to determine the bioavailability of a new glucose-lowering agent, Compound X, they have developed. The rate of decrease in concentration (C) with time can be described by the equation dC dt = kC n, where n is the "order" of the rate process. The following pharmacological definition has been taken from the Pharmacology and Experimental Therapeutics Department Glossary at Boston University School of Medicine. Pharmacokinetics is the movement of a drug through the body's biological systems, these processes include absorption, distribution, bioavailability, metabolism, and elimination. Thus F = (149.78/67.43) x (100/250) = 0.89. There are different ways to calculate AUC. For repeated bolus dosing, the OSCILLATIONS in concentration that give rise to peaks and troughs. The standard method for calculating AUC parameters is the linear-up/log-down trapezoidal method. The bioavailability of a drug depends in part on its formulation. Vancomycin regimens can be calculated both empirically (without any prior doses) or using one or two vancomycin levels. pp687-689. Trapezoidal Rule (Mathematical Method). CALCULUS. A PK profile is generally the result of four key physiological events: absorption, distribution, metabolism, and excretion, typically referred to as ADME. Pharmacokinetics is the study of what the body does to the drug, and Pharmacodynamics is the study of what the drug does to the body. Clearance is equal to the rate at which a drug is removed from plasma(mg/min) divided by the concentration of that drug in the plasma (mg/mL). Structure. 17. AUC = Area under the concentration-time curve. The amount eliminated by the body (mass) = clearance (volume/time) * AUC (mass*time/volume). The AUC of daily (AUC 0-24) plasma concentrations was calculated with blood samples collected before (time 0) and at 2, 4, 6 and 8 h after intravenous administration. So let's prepare the data and train the model: Now let's calculate the ROC and AUC and then plot them by using the matplotlib library in Python: The curve that you can see in the above figure is known as the ROC curve and the area under the curve in the above figure is AUC. Calculate Area Under the Curve(AUC) and the first Moment Curve(AUMC) in two ways; 'linear trapezoidal method' or 'linear-up and log-down' method. PHARMACOKINETIC PARAMETERS is a topic covered in the Guide to Diagnostic Tests. vector values of independent variable, usually time, vector values of dependent variable, usually concentration, either of "Linear" or "Log" to indicate the way to calculate AUC and AUMC. Pharmacokinetics can vary from person to person and it is affected by age, gender, diet, environment, body weight and pregnancy, patient's pathophysiology, genetics and drug- drug or food-drug interactions. Permission has been granted for its use in this blog. The GlobalRPh vancomycin single-level calculator uses the Vd recommended in Bauer's text: 0.7 L/kg. Table with two columns, AUC and AUMC; the first column values are cumulative AUCs and the second column values cumulative AUMCs. #areaunderthecurve #auc #biopharmaceutics #pharmacokinetics #pharmacyd #pharmacydbyasimArea under the curve or AUC, represents the total integrated area under the plasma level time profile, and express the total amount of active drug, which reaches the systemic circulation. Parameters obtained from plasma concentrations. The main ways the human body handles drugs are listed below. Historically, AUC was calculated using Clinical Pharmacokinetics and Pharmacodynamics - Concepts and . Pharmacokinetics is broadly defined as the bodys effect on a drug. We report a large CyA-pharmacokinetics study, which was performed to develop a strategy to calculate AUC 04. Target concentration = 5 mg/L. Typically, the first level will be a post infusion peak and the second level is a trough level. So, feel free to use this information and benefit from expert answers to the questions you are interested in! 2.2 Volume of Distribution. Pharmacokinetic models consider drugs in the body to be in a dynamic state. Initially, C (in) = initial C, thereafter, it = Ct (C at specified time after start) Relating ER, CL, & Ke ER = constant if Flow, Vd, and renal function are constant. 4th ed. Simply put, PK describes what the body does to the drug, and PD describes what the drug does to the body. The Cmin was defined as the concentration before the administration and the maximum plasma concentration ( Cmax) as the concentration at the end of the infusion. t1 2. This parameter reports the number of non-missing observations used in the analysis of the profile (time is at or after dosing time, the observation is numeric, and the volume is positive for urine models). The triangle will have area TPR*FRP/2 , the trapezium (1-FPR)*(1+TPR)/2 = 1/2 - FPR/2 + TPR/2 - TPR*FPR/2 . This is your one-stop encyclopedia that has numerous frequently asked questions answered. bioavailability. Corresponds to the Css of IV infusion. The power model assumes a linear relationship between natural log-transformed pharmacokinetic exposure parameter (AUC last, AUC inf, and Cmax) and natural log-transformed dose; ln (PK) = 0 + 1 ln (dose). Elimination Rate Constant (k) The rate constant is calculated from the slope (k/2.303) of the blood concentration and time curve (loglinear scale) as shown in Figure 2a (Figure 2b shows the same data on linear scale). AUC is the target area under the curve (concentration versus time). Of course we can calculate the bioavailability of the oral dosage form using the dose adjusted AUC ratio. Compute the area of all trapezoids and sum them to give the AUC up to the last sample drawn. Now, we have got a complete detailed explanation and answer for everyone, who is interested! These are all a part of PK. In bioequivalence studies, the maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. The 1-compartment drug models are not hard-coded into the APK program. Parameters related to plasma/blood measurements specific to steady state dosing regimen. They have previously studied the pharmacokinetics of both IV and oral forms of this drug. 4: C p = C p 0 e ( k t) This equation describes how an initial drug concentration (Cp 0) declines to a final drug concentration (Cp) over a specified period of . Intermittent Hemodialysis Calculator: The key to this calculator is to target a pre-dialysis level of about 20 mcg/ml because this will give a daily AUC of about 500. This vancomycin calculator uses three "core" clinical pharmacokinetic equations that are well described for intermittent intravenous infusions assuming a one-compartment model. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. AUC=FDCL. The difference between pharmacokinetics and pharmacodynamics is that pharmacokinetics (PK) is defined as the movement of drugs through the body, whereas pharmacodynamics (PD) is defined as the bodys biological response to drugs. Css = concentration of drug in plasma at steady state. From this we can calculate an average absorption rate constant = 1/MAT = 1/0.88 = 1.14 hr -1 . For more information on customizing the embed code, read Embedding Snippets. A drug used to treat cancer is the carboplatin. The half-life of a drug can be determined using the following equation: t1/2 = (0.7 x Vd) / Cl, where Vd is volume of distribution and Cl is clearance. If the base (b) is e, then it is described as natural logarithm (Ln). (Remember that ln is the natural logarithm, to the base e, rather than the common logarithm or logarithm to the base 10; ln X=2.303 log X.) Drugs that have a volume of distribution 7 4 L or less are thought to be confined to the plasma, or liquid part of the blood. and 25.000 on C27 (192 hours, or 1 half-life), etc. Welcome to FAQ Blog! general logarithm. Non-compartmental estimation of the area under the concentration versus time curve (AUC) to the last time point, AUC to infinity, area under the first moment curve (AUMC) to infinity, mean residence time (MRT), non . CL=total plasma clearance. This calculator determines pharmacokinetic . (AUC = Dose/Clearance)* Importance of AUC: In toxicology, AUC can be used as a measure of drug exposure. In Biopharmaceutics, it is the most important parameter, in evaluating the bioavailability of a drug, from different dosage forms, as it represents the extent of absorption. In Pharmacokinetics, Drug AUC values can be used to determine other pharmacokinetic parameters, such as clearance or bioavailability. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person's genetic makeup. It enables the following processes to be quantied: Absorption Distribution Metabolism Excretion These pharmacokinetic processes, often referred to as ADME, determine the drug concentration in the body when medicines are prescribed. In summary : MAT = MRT (PO) - MRT (iv) Figure XIX-15 Plot of Cp versus Time (IV) N_Samples. Commonly Used Pharmacokinetics Terms AUC: Area Under the Curve is defined as the "total exposure to the drug" within a certain window of time. The model captures key features in experimental time courses on ofloxacin accumulation: initial uptake; two-phase response; and long-term acclimation.In combination with experimental data, the model provides estimates of import and export rates in each phase, the time of entry into the second phase, and the decrease of internal. Parameters related to z. Parameters related to plasma/blood measurements. If the volume is between 7 4 and 15 7 L, the drug is thought to be distributed throughout the blood (plasma and red blood cells). This formula can be used to calculate the carboplatin dose accurately in order to obtain a target AUC by using only the GFR. Zero-order After an extravascular administration ( Figure 4) t. The area, therefore, is X* ( [ (Y1+Y2)/2]-Baseline]. The company has obtained the following information regarding the IV formulation of Compound X: Administration of 50 mg of Compound X by IV yields an area . Estimate Ideal body weight in (kg) Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Pharmacokinetics (PK) parameters are typically calculated by non-compartmental analysis . SimBiology lets you calculate NCA parameters from concentration-time data. Nonlinear pharmacokinetics is the characteristic of drugs that briefs that the absorption and bioavailability can cause increases in drug concentrations that are disproportionately high or low relative to the change in dose. Then, Calculate the area. The unreliability of the data is not due to a calculation error. Does pharmacokinetics include biotransformation? How do you calculate GFR for carboplatin? Vancomycin single level . * Methods to determine AUCThere are various methods available to determine the AUC, which includes. This characteristic of drugs only alters with changes in dosage of drugs. The liter units cancel. It does not count points inserted by engine, e.g., inserted at dosing time. Extraction ratio (ER) is the fraction of drug that is removed from the blood or plasma as it crosses the eliminating organ (e.g. Prism uses this formula repeatedly for each adjacent pair of points defining the curve. In pharmacokinetic calculations, the time points are usually from time 0 to the last quantifiable point. It is expressed in units of time 1. The data must contain a time column, a concentration column, and a dose column that defines dose amounts. Formula Volume of Distribution = Total Dose / Concentration. Pharmacodynamics (sometimes described as what a drug does to the body) is the study of the biochemical, physiologic, and molecular effects of drugs on the body and involves receptor binding. Bioavailability = 50% Dosing Interval = 12 h. Dosing Rate = 2 (L/h) x 5 (mg/L) / 0.50 = 20 mg/h. We will consider two cases: zero-order (n=0) and first-order (n=1). CrCl = [ (140 - age) x IBW] / (Scr x 72) (x 0.85 for females) Note: if the ABW (actual body weight) is less than the IBW use the. The term relative bioavailability is used to compare two different extravascular routes of drug administration. You may tailor each drug model to fit your patient population, or you may create your own models. Since the first-order elimination rate constants ke and can be calculated by dividing VD by Cl, the half-life of a xenobiotic that follows a one- or two-compartment model can be calculated as follows: (1) one-compartment model t1 / 2 = 0.693/ke and (2) two-compartment model t1 / 2 = 0.693/. down="Log" means linear-up and log-down method. How do you calculate AUC manually? Another useful metric is to calculate the fraction of the total AUC that is due to the extrapolated AUC. 1. Drug . C0 can be determined from a direct measurement or estimated by back- extrapolation from concentrations determined at any time after the dose. Value. As an example, calculate the following loading dose (Mass(mg)/Time(h)): Clearance = 2 L/h. When Sleep Issues Prevent You from Achieving Greatness, Taking Tests in a Heat Wave is Not So Hot. Trough was drawn 12.5 hours after the last dose. As a rule, for example, sedatives can potentiate each other. Pharmacokinetics provides a mathematical basis to assess the time course of drugs and their effects in the body. Cmax is highly correlated with the area under the curve (AUC) contrasting blood concentration with time. Instead, it returns 50 on C3 (after 8 hours), 48.577 on C4 (16 hours), (.) The calculation of the pharmacokinetic parameters. AUC and bioavailability [ edit] In pharmacokinetics, bioavailability generally refers to the fraction of drug that is absorbed systemically and is thus available to produce a biological effect. This vancomycin calculator uses pharmacokinetic population estimates, Bayesian modeling, and the Sawchuk-Zaske method to calculate a vancomycin dosing regimen for an adult patient. There are four main components of pharmacokinetics: liberation, absorption, distribution, metabolism and excretion (LADME). Linear Pharmacokinetics ,the characteristic of drugs that indicates the instantaneous rate of change in drug concentration depends only on the current concentration. ] summarized the following: (a) clinical effectiveness is best achieved when targeting the ratio of the area under the serum drug concentration-versus-time curve (auc) and the minimum inhibitory concentration (mic) of the organism (auc/mic), specifically when auc/mic is 400 using broth microdilution for staphylococcus aureus including Is pharmacokinetics the same as mechanism of action? Definition. If you can remember this equation, you can pretty much extrapolate all the others. Pharmacokinetics represents the absorption, distribution, metabolism, and elimination of drugs from the body. During absorption phase, absorption rate constant (ka) is desired to be greater than elimination rate constant (ke). The following step-by-step example shows how to calculate AUC for a logistic regression model in R. Step 1: Load the Data Is it healthier to drink herbal tea hot or cold? After an intravascular administration ( Figure 3) AUC=area under the curve of a plasma concentration versus time profile. The area from the first to last data point can then be calculated by adding the areas together. t1/2 =elimination half-life. The time following drug administration at which the peak concentration of Cmax occurs, tp (for any route of administration but the intravenous), is given by tp = (ln ka ln kel )/(ka kel). These parameters are clearance, volume of distribution, half-life, and bioavailability. Thus, PK PD assay and data analysis results are essential to any ECTD submission. Drug action usually occurs in three phases: Pharmaceutical phase. Among many pharmacokinetic approaches and modeling analyses, traditional NCA parameters. PK PD analysis study links drug exposure to therapeutic effect measures so drug developers can better understand the relationships between exposure, efficacy, and toxicity. For drugs eliminated by first-order kinetics from a single-compartment system, Cmax, after n equal doses given at equal intervals is given by C0(1 fn )/(1 f) = Cmax, and Cmin = Cmax C0. 2 Basic & Applied Pharmacokinetics Self Assessment Dosing Strategies Infants A population pharmacokinetic analysis of vanco-mycin concentration-time data obtained from 374 infants with a median postnatal age of 70 days and a median gestational age of 33.5 weeks yielded the following equation: CL vanc (L/hr) = [W ((0.028/S Cr) + The parameters (highlighted below in blue) are found in the drug model database and are fully user-editable. . Pharmacodynamics defines the relationship between plasma and tissue drug and/or metabolite concentrations, time, and therapeutic response. You can divide the space into 2 parts: a triangle and a trapezium. This is often measured by quantifying the "AUC". Volume of distribution (Vd), represents the apparent volume into which the drug is distributed to provide the same concentration as it currently is in blood plasma. The two broad divisions of pharmacology are pharmacokinetics and pharmacodynamics. How do you calculate t1 2 of a drug? Pharmacokinetic phase. (AUC) contrasting blood concentration with time. The following page describes all the parameters computed by the non compartmental analysis. Are you a visual learner interested in learning psychopharmacology? In Pharmacokinetics, Drug AUC values can be used to determine other pharmacokinetic parameters, such as clearance or bioavailability. The half-life will remain constant, irrespective of how high the concentration. How do pharmacokinetics and pharmacodynamics compare quizlet? ACC admission Vasopressor administration Weight >/= 101 Kg History of acute or chronic kidney injury Empiric vancomycin doses >4 gm/day Prolonged courses (>5 days) Unstable renal function at baseline Initial trough (within 96 hours) level >20 mcg/mL Elevated AUC levels 600-800 within 48 hrs of initiation half-life of the drug (t 1/2), and the area under the curve (AUC), and predict concentrations at given time points. Throughout the drug development program, pharmacokinetics is a tool used to link exposure to efficacy and safety, and it assists in the determination of dosages of marketed drugs; for this reason, PK data are an important part of the information provided to clinicians.
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