This document summarizes an evaluation of modeling approaches for determining antemortem (before death) ethanol concentrations and considerations for postmortem ethanol generation and transport. It compares physiologically-based pharmacokinetic (PBPK) modeling approaches and the standard Widmark equation approach. It also presents an empirical modeling approach that combines PBPK modeling of antemortem concentrations with analysis of postmortem ethanol concentrations to more accurately estimate blood ethanol concentration at time of death. Additionally, it describes factors that can affect postmortem ethanol levels, such as production of ethanol by microorganisms after death.
Immunosuppressants in Blood at OpAns Poster-MicroLiterRick Youngblood
This document describes an automated method for extracting and analyzing three immunosuppressant drugs (cyclosporine, sirolimus, and tacrolimus) from whole blood samples using solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS). Instrument Top Sample Preparation (ITSP) was used to automate the SPE process, improving sample throughput and reducing waste compared to offline SPE methods. The method showed good linearity, precision, sensitivity, and low carryover between samples.
Automated hplc screening of newborns for sickle cell anemia juarez1precioso
This document describes an automated HPLC method used to screen over 2.5 million newborn dried blood samples for hemoglobinopathies like sickle cell anemia. The method uses cation exchange chromatography to separate and quantify hemoglobins F, A, S, C, E, and D. It was found to have high throughput of 1 sample per minute, small sample volume needs, precision of variant quantification within 14-18%, and detection limits of 0.5% for Hb S and C and 1.0% for other variants. Shortcomings included the need for manual sample loading and lack of sample identification barcodes. The method was shown to accurately detect cases of sickle cell disease in newborns over 4 years of
CT3 Educational Material provides an overview of the Clinical Toxicology III (CT3) lab at ARUP, which performs qualitative toxicology analysis on pain medication management and drug abuse during pregnancy samples. The document discusses the chemistry and techniques used in the lab, including ELISA screening, TOF mass spectrometry analysis, and supported liquid extraction sample preparation. It also covers important regulations like HIPAA that govern protected health information and patient privacy in medical testing.
This document provides an overview of renal physiology. It discusses the major topics of body fluid compartments, the functional anatomy of the kidney, and basic renal mechanisms including glomerular filtration, tubular reabsorption, and tubular secretion. Glomerular filtration typically filters around 180 liters of fluid per day, while only 1-2 liters are excreted as urine through reabsorption in the tubules. Tubular reabsorption conserves essential substances like water, glucose, electrolytes, and bicarbonate that were filtered at the glomerulus. The kidney regulates fluid and solute balance through these complex and highly integrated filtration, reabsorption, and secretory processes.
Investigating Novel Methods to Reduce Cholesterol Levels (Research Report)Tony Ng
In this study, we used everyday food items such as lactic acid bacteria (found in yogurt), sunflower seeds and kidney beans, to either absorb cholesterol in the gut or inhibit cholesterol synthesis in the body. Findings can potentially provide doctors and health experts with an alternative to statins, cholesterol-lowering drugs that may lead to side effects. As future work, we can explore the chemical compound present in the natural extracts that help inhibit cholesterol synthesis, and if possible, carry out trials in vivo to better determine the effects of these extracts.
Immunosuppressants in Blood at UWMC Poster-MicroLiterRick Youngblood
The document summarizes a study comparing an automated solid phase extraction instrument called the Instrument Top Sample Prep (ITSP) to a Gilson XL4 liquid handler for extracting tacrolimus, sirolimus, and cyclosporine from whole blood samples. Results showed that both instruments produced analytically acceptable data, but the ITSP used 60% less reagent, 40% less sorbent, and fewer disposables while achieving similar performance. The ITSP also had a smaller footprint and allowed for unattended sample processing and integration with LC/MS for quick turnaround of immunosuppressant drug level results in a clinical setting.
This study compared the quantification of free light chains (FLC) in serum and urine of multiple myeloma patients using immunonephelometry versus electrophoresis. Immunonephelometry showed FLC levels up to 9-fold and 11-fold higher in serum and urine respectively compared to electrophoresis. Bland-Altman plots also showed poor reproducibility and agreement between the two methods for FLC quantification. The overestimation was greater at higher FLC values, suggesting immunonephelometry has limitations including poor post-dilution linearity. Given international guidelines recommend different methods for serum versus urine FLC, values cannot be directly compared between the two quantification methods.
Immunosuppressants in Blood at OpAns Poster-MicroLiterRick Youngblood
This document describes an automated method for extracting and analyzing three immunosuppressant drugs (cyclosporine, sirolimus, and tacrolimus) from whole blood samples using solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS). Instrument Top Sample Preparation (ITSP) was used to automate the SPE process, improving sample throughput and reducing waste compared to offline SPE methods. The method showed good linearity, precision, sensitivity, and low carryover between samples.
Automated hplc screening of newborns for sickle cell anemia juarez1precioso
This document describes an automated HPLC method used to screen over 2.5 million newborn dried blood samples for hemoglobinopathies like sickle cell anemia. The method uses cation exchange chromatography to separate and quantify hemoglobins F, A, S, C, E, and D. It was found to have high throughput of 1 sample per minute, small sample volume needs, precision of variant quantification within 14-18%, and detection limits of 0.5% for Hb S and C and 1.0% for other variants. Shortcomings included the need for manual sample loading and lack of sample identification barcodes. The method was shown to accurately detect cases of sickle cell disease in newborns over 4 years of
CT3 Educational Material provides an overview of the Clinical Toxicology III (CT3) lab at ARUP, which performs qualitative toxicology analysis on pain medication management and drug abuse during pregnancy samples. The document discusses the chemistry and techniques used in the lab, including ELISA screening, TOF mass spectrometry analysis, and supported liquid extraction sample preparation. It also covers important regulations like HIPAA that govern protected health information and patient privacy in medical testing.
This document provides an overview of renal physiology. It discusses the major topics of body fluid compartments, the functional anatomy of the kidney, and basic renal mechanisms including glomerular filtration, tubular reabsorption, and tubular secretion. Glomerular filtration typically filters around 180 liters of fluid per day, while only 1-2 liters are excreted as urine through reabsorption in the tubules. Tubular reabsorption conserves essential substances like water, glucose, electrolytes, and bicarbonate that were filtered at the glomerulus. The kidney regulates fluid and solute balance through these complex and highly integrated filtration, reabsorption, and secretory processes.
Investigating Novel Methods to Reduce Cholesterol Levels (Research Report)Tony Ng
In this study, we used everyday food items such as lactic acid bacteria (found in yogurt), sunflower seeds and kidney beans, to either absorb cholesterol in the gut or inhibit cholesterol synthesis in the body. Findings can potentially provide doctors and health experts with an alternative to statins, cholesterol-lowering drugs that may lead to side effects. As future work, we can explore the chemical compound present in the natural extracts that help inhibit cholesterol synthesis, and if possible, carry out trials in vivo to better determine the effects of these extracts.
Immunosuppressants in Blood at UWMC Poster-MicroLiterRick Youngblood
The document summarizes a study comparing an automated solid phase extraction instrument called the Instrument Top Sample Prep (ITSP) to a Gilson XL4 liquid handler for extracting tacrolimus, sirolimus, and cyclosporine from whole blood samples. Results showed that both instruments produced analytically acceptable data, but the ITSP used 60% less reagent, 40% less sorbent, and fewer disposables while achieving similar performance. The ITSP also had a smaller footprint and allowed for unattended sample processing and integration with LC/MS for quick turnaround of immunosuppressant drug level results in a clinical setting.
This study compared the quantification of free light chains (FLC) in serum and urine of multiple myeloma patients using immunonephelometry versus electrophoresis. Immunonephelometry showed FLC levels up to 9-fold and 11-fold higher in serum and urine respectively compared to electrophoresis. Bland-Altman plots also showed poor reproducibility and agreement between the two methods for FLC quantification. The overestimation was greater at higher FLC values, suggesting immunonephelometry has limitations including poor post-dilution linearity. Given international guidelines recommend different methods for serum versus urine FLC, values cannot be directly compared between the two quantification methods.
Preliminary Thesis Research PresentationApryl Boyle
This document summarizes research into the variability in metabolism of chloral hydrate by human hepatocytes. The study aimed to optimize an assay to measure the metabolism of trichloroethylene (TCE), a suspected carcinogen, through chloral hydrate. The working hypothesis was that genetic variability in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) would alter TCE metabolism. The optimized assay showed wide variability between hepatocyte samples in the Michaelis-Menten kinetic parameters for the conversion of chloral hydrate to trichloroethanol and trichloroacetic acid. Future work will involve further optimization, epidemiological studies, and development of a physiologically-based pharmacokinetic
Chloral hydrate is metabolized to both the carcinogenic metabolite trichloroacetate (TCA) and the non-carcinogenic metabolite trichloroethanol (TCE-OH) in the liver. This study found significant variability in human liver samples' ability to metabolize chloral hydrate, as measured by the Km and Vmax values for TCA and TCE-OH formation. Both ALDH and ADH, the enzymes involved in metabolizing chloral hydrate, show polymorphisms in humans, predicting inter-individual differences in disposition toward the carcinogenic versus non-carcinogenic pathways. This variability could result in sub-populations having greater risk of
Application of Physiologically-based Kinetic Models in Exposure ModelingIES / IAQM
This document summarizes a land condition symposium presentation on applying physiologically-based kinetic models in land contamination exposure modelling. The presentation introduced key terms like bioaccessibility and bioavailability, and described a study that used physiologically-based pharmacokinetic (PBPK) models to improve understanding of actual human exposure to contaminants like arsenic, cadmium, chromium, nickel, and lead in soil. Soil, produce, blood, and urine samples were collected and analyzed from allotment users. PBPK models were produced and evaluated against literature data. The models can estimate uptake fractions and relative
Sensitive and selective detection of chemical residues in hops is necessary to ensure protection of consumers and the environment. Methods using LC-MS provide efficient and effective detection of chemical residues in a complex sample matrix such as hops. Presented here is an LC-MS method for detection of over 150 analytes in hops and a market survey of over 50 different hops pellets samples.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Metabolism is the set of life-sustaining chemical transformations within the cells of living organisms .The metabolome is the global collection of all low molecular weight metabolites that are produced by cells during metabolism, and provides a direct functional readout of cellular activity and physiological status. In this presentation i have given the list of various Metabolomic databases and metabolite databases. In addition to this there is a brief description about SMPDB and HMDB and BioTransformer
This document summarizes a study examining the anti-proliferative effects of Arisaema intermedium lectin (AIL) on human colon cancer cells. AIL was purified from Arisaema intermedium tubers and its effects were tested on HCT-15 colon cancer cells. MTT assays showed AIL inhibited the growth of HCT-15 cells in a dose-dependent manner, with 53% inhibition at 100 μg/mL AIL. Further experiments found AIL treatment led to DNA fragmentation, changes in nucleic acid content, cell morphology changes, and decreased cell viability, indicating AIL induces apoptosis in HCT-15 cells. The results suggest AIL has anti-cancer properties and works through an apoptotic
The document summarizes a two-compartment pharmacokinetic model for analyzing contrast agent behavior. The model includes compartments for plasma, extracellular space (EES), and tumors. It defines variables like contrast agent concentrations and transfer rates between compartments. The summary also outlines how signal intensity data from MRI scans can be converted to contrast agent concentrations using calibration curves.
CYP2A6_HPLC_PK_2015 New Simple Method for Coumarin in Liver Cytochrome of RatsWael Ebied
This document describes the development and validation of a new liquid chromatography method for determining coumarin and its 7-hydroxy metabolite as a marker of cytochrome P450 2A6 activity in rats. The method uses a C18 column and isocratic mobile phase to separate coumarin, 7-hydroxycoumarin, and an internal standard. The method was validated and showed good linearity, precision, and accuracy. This validated method was then applied to study the effect of resveratrol, sulforaphane, and thymoquinone on hepatic CYP2A6 activity in spontaneously hypertensive rats.
This document summarizes key concepts in clinical toxicology related to pain management chemistry, including glucuronide pathways, solid phase extraction (SLE) columns, chromatography, and mass spectrometry. It discusses how glucuronidation is a metabolic process that attaches molecules to analytes for excretion, and how β-glucuronidase enzyme is used to break these bonds during analysis. It also describes how SLE columns extract analytes from samples, how liquid chromatography separates molecules, and how time-of-flight mass spectrometry identifies compounds by mass.
Methods and Approaches for Defining Mechanism Signatures from Human Primary C...BioMAP® Systems
The document describes methods for using human primary cell-based disease models called BioMAP systems to define mechanism signatures of compounds. BioMAP systems analyze compound profiles across multiple readouts in various cell types to classify compounds according to their mechanisms of action or toxicity pathways. High reproducibility is shown for compound profiles even across different experiments and cell donors.
This document outlines the development of a universal design methodology curriculum at San Francisco State University. It discusses several key components for implementing such a curriculum, including lecture materials, professional reviews/critiques, and research through workshops and focus groups.
Thematic areas that would be covered include design, health, social, legal, and economic perspectives as they relate to universal design. Specific topics mentioned are universal design principles, inclusive target markets, aging populations, independent living, intergenerational benefits, disability rights policies, and quantifying universal design benefits and appeals.
A 5-phase methodology is presented: discovery/understanding through research; interpreting findings; exploring concepts and solutions; evaluating ideas; and implementing tangible solutions relative to universal design
The document describes Emerald Feng's work on physiologically-based pharmacokinetic (PBPK) modeling. It discusses how PBPK models are used to quantify absorption, distribution, metabolism, and excretion of chemicals for health risk assessments. It notes that PBPK models vary in complexity from 2-compartment to several compartments. Key parameters like organ flows and compartment partitioning are influenced by intrinsic and extrinsic factors. Molecular descriptors derived from chemical properties are important for PBPK modeling and predicting absorption, distribution, metabolism, and excretion. The document also discusses related topics like quantitative structure-activity relationship modeling and converting PBPK models to a mobile application format.
Lixoft was incorporated in 2011 to commercialize the Monolix population modeling software and further its development. It has 4 employees and collaborates with Inria on research. Monolix 4.0 and 4.1 saw initial commercial success with several contracts in big pharma. Lixoft plans to expand Monolix's capabilities to new areas like pharmacogenetics and PBPK modeling, develop a clinical trial simulator, and establish itself as a leader in modeling and simulation for drug development within 3 years.
Traditional software development methodologies were not well-suited to frequent changes in requirements. Newer agile methodologies like Agile and XP emphasize adaptability, iterative development, and communication between developers and customers. These methodologies may provide better efficiency and quality outcomes than traditional predictive models. While documentation is still important, agile focuses on executable work products over speculative documentation and emphasizes that documentation should have clear benefits outweighing production costs. Choosing the right methodology requires considering an organization's goals and ability to manage challenges in a dynamic business environment.
Agile, eXtreme Programming (XP), and software prototyping are approaches to software development. Agile focuses on individuals, interactions, working software, and responding to change over processes, tools, documentation, and plans. XP uses pair programming, continuous integration, refactoring, and frequent releases. It also emphasizes shared understanding. Software prototyping identifies requirements early, gets users involved, and enhances or discards prototypes to reduce time and costs and ensure user satisfaction. Different methodologies work best depending on project size and needs.
Software Agility - Necessary...but not SufficientTathagat Varma
My presentation at Agile Tours 2012 at Bangalore. In this presentation, I have taken a hard look at how the basic agile adoption appears to be rather ineffective in the face of today's problems that are much more complex, dynamic and uncertain. I outline hat I consider as inadequacies of agility as we understand today. I also discuss Lean Startup framework as a better way to address some of these shortcomings. Feedback welcome...
A new approach towards agile and xp software development methodologyPatanjali Kashyap
The document discusses a proposed new software development methodology that incorporates holistic intelligence factors. It considers emotional (EQ), social (SQ), and moral (MQ) intelligence in addition to technical skills. The methodology would develop an organizational behavioral database to match employees' strengths and weaknesses to projects based on intelligence parameters and histories. This aims to improve overall efficiency and productivity by selecting the right people for each job.
Audrys Kažukauskas - Introduction into Extreme ProgrammingAgile Lietuva
Extreme Programming might not be a silver bullet, but in software development it is almost that. Managers get all the bells and whistles you would expect from an agile process, whilst developers are equipped with a set of principles and practices, which almost inevitably improve the codebase and enable frequent delivery of quality software. In fact, many teams, which use other software development processes (Scrum, for instance) eventually end up adopting quite a few XP practices. I'll give you an introduction into XP, share my experiences and provide references to XP material for learning more about XP.
The document provides an overview of Extreme Programming (XP), the most widely used agile development process originally proposed by Kent Beck. It discusses the key practices of XP including planning with user stories, small iterative releases, simple design practices like CRC cards, test-driven development, pair programming, continuous integration, and collective code ownership. The document notes that XP works well for projects with dynamically changing requirements, risky projects, or small development groups of up to 100 people.
Preliminary Thesis Research PresentationApryl Boyle
This document summarizes research into the variability in metabolism of chloral hydrate by human hepatocytes. The study aimed to optimize an assay to measure the metabolism of trichloroethylene (TCE), a suspected carcinogen, through chloral hydrate. The working hypothesis was that genetic variability in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) would alter TCE metabolism. The optimized assay showed wide variability between hepatocyte samples in the Michaelis-Menten kinetic parameters for the conversion of chloral hydrate to trichloroethanol and trichloroacetic acid. Future work will involve further optimization, epidemiological studies, and development of a physiologically-based pharmacokinetic
Chloral hydrate is metabolized to both the carcinogenic metabolite trichloroacetate (TCA) and the non-carcinogenic metabolite trichloroethanol (TCE-OH) in the liver. This study found significant variability in human liver samples' ability to metabolize chloral hydrate, as measured by the Km and Vmax values for TCA and TCE-OH formation. Both ALDH and ADH, the enzymes involved in metabolizing chloral hydrate, show polymorphisms in humans, predicting inter-individual differences in disposition toward the carcinogenic versus non-carcinogenic pathways. This variability could result in sub-populations having greater risk of
Application of Physiologically-based Kinetic Models in Exposure ModelingIES / IAQM
This document summarizes a land condition symposium presentation on applying physiologically-based kinetic models in land contamination exposure modelling. The presentation introduced key terms like bioaccessibility and bioavailability, and described a study that used physiologically-based pharmacokinetic (PBPK) models to improve understanding of actual human exposure to contaminants like arsenic, cadmium, chromium, nickel, and lead in soil. Soil, produce, blood, and urine samples were collected and analyzed from allotment users. PBPK models were produced and evaluated against literature data. The models can estimate uptake fractions and relative
Sensitive and selective detection of chemical residues in hops is necessary to ensure protection of consumers and the environment. Methods using LC-MS provide efficient and effective detection of chemical residues in a complex sample matrix such as hops. Presented here is an LC-MS method for detection of over 150 analytes in hops and a market survey of over 50 different hops pellets samples.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Metabolism is the set of life-sustaining chemical transformations within the cells of living organisms .The metabolome is the global collection of all low molecular weight metabolites that are produced by cells during metabolism, and provides a direct functional readout of cellular activity and physiological status. In this presentation i have given the list of various Metabolomic databases and metabolite databases. In addition to this there is a brief description about SMPDB and HMDB and BioTransformer
This document summarizes a study examining the anti-proliferative effects of Arisaema intermedium lectin (AIL) on human colon cancer cells. AIL was purified from Arisaema intermedium tubers and its effects were tested on HCT-15 colon cancer cells. MTT assays showed AIL inhibited the growth of HCT-15 cells in a dose-dependent manner, with 53% inhibition at 100 μg/mL AIL. Further experiments found AIL treatment led to DNA fragmentation, changes in nucleic acid content, cell morphology changes, and decreased cell viability, indicating AIL induces apoptosis in HCT-15 cells. The results suggest AIL has anti-cancer properties and works through an apoptotic
The document summarizes a two-compartment pharmacokinetic model for analyzing contrast agent behavior. The model includes compartments for plasma, extracellular space (EES), and tumors. It defines variables like contrast agent concentrations and transfer rates between compartments. The summary also outlines how signal intensity data from MRI scans can be converted to contrast agent concentrations using calibration curves.
CYP2A6_HPLC_PK_2015 New Simple Method for Coumarin in Liver Cytochrome of RatsWael Ebied
This document describes the development and validation of a new liquid chromatography method for determining coumarin and its 7-hydroxy metabolite as a marker of cytochrome P450 2A6 activity in rats. The method uses a C18 column and isocratic mobile phase to separate coumarin, 7-hydroxycoumarin, and an internal standard. The method was validated and showed good linearity, precision, and accuracy. This validated method was then applied to study the effect of resveratrol, sulforaphane, and thymoquinone on hepatic CYP2A6 activity in spontaneously hypertensive rats.
This document summarizes key concepts in clinical toxicology related to pain management chemistry, including glucuronide pathways, solid phase extraction (SLE) columns, chromatography, and mass spectrometry. It discusses how glucuronidation is a metabolic process that attaches molecules to analytes for excretion, and how β-glucuronidase enzyme is used to break these bonds during analysis. It also describes how SLE columns extract analytes from samples, how liquid chromatography separates molecules, and how time-of-flight mass spectrometry identifies compounds by mass.
Methods and Approaches for Defining Mechanism Signatures from Human Primary C...BioMAP® Systems
The document describes methods for using human primary cell-based disease models called BioMAP systems to define mechanism signatures of compounds. BioMAP systems analyze compound profiles across multiple readouts in various cell types to classify compounds according to their mechanisms of action or toxicity pathways. High reproducibility is shown for compound profiles even across different experiments and cell donors.
This document outlines the development of a universal design methodology curriculum at San Francisco State University. It discusses several key components for implementing such a curriculum, including lecture materials, professional reviews/critiques, and research through workshops and focus groups.
Thematic areas that would be covered include design, health, social, legal, and economic perspectives as they relate to universal design. Specific topics mentioned are universal design principles, inclusive target markets, aging populations, independent living, intergenerational benefits, disability rights policies, and quantifying universal design benefits and appeals.
A 5-phase methodology is presented: discovery/understanding through research; interpreting findings; exploring concepts and solutions; evaluating ideas; and implementing tangible solutions relative to universal design
The document describes Emerald Feng's work on physiologically-based pharmacokinetic (PBPK) modeling. It discusses how PBPK models are used to quantify absorption, distribution, metabolism, and excretion of chemicals for health risk assessments. It notes that PBPK models vary in complexity from 2-compartment to several compartments. Key parameters like organ flows and compartment partitioning are influenced by intrinsic and extrinsic factors. Molecular descriptors derived from chemical properties are important for PBPK modeling and predicting absorption, distribution, metabolism, and excretion. The document also discusses related topics like quantitative structure-activity relationship modeling and converting PBPK models to a mobile application format.
Lixoft was incorporated in 2011 to commercialize the Monolix population modeling software and further its development. It has 4 employees and collaborates with Inria on research. Monolix 4.0 and 4.1 saw initial commercial success with several contracts in big pharma. Lixoft plans to expand Monolix's capabilities to new areas like pharmacogenetics and PBPK modeling, develop a clinical trial simulator, and establish itself as a leader in modeling and simulation for drug development within 3 years.
Traditional software development methodologies were not well-suited to frequent changes in requirements. Newer agile methodologies like Agile and XP emphasize adaptability, iterative development, and communication between developers and customers. These methodologies may provide better efficiency and quality outcomes than traditional predictive models. While documentation is still important, agile focuses on executable work products over speculative documentation and emphasizes that documentation should have clear benefits outweighing production costs. Choosing the right methodology requires considering an organization's goals and ability to manage challenges in a dynamic business environment.
Agile, eXtreme Programming (XP), and software prototyping are approaches to software development. Agile focuses on individuals, interactions, working software, and responding to change over processes, tools, documentation, and plans. XP uses pair programming, continuous integration, refactoring, and frequent releases. It also emphasizes shared understanding. Software prototyping identifies requirements early, gets users involved, and enhances or discards prototypes to reduce time and costs and ensure user satisfaction. Different methodologies work best depending on project size and needs.
Software Agility - Necessary...but not SufficientTathagat Varma
My presentation at Agile Tours 2012 at Bangalore. In this presentation, I have taken a hard look at how the basic agile adoption appears to be rather ineffective in the face of today's problems that are much more complex, dynamic and uncertain. I outline hat I consider as inadequacies of agility as we understand today. I also discuss Lean Startup framework as a better way to address some of these shortcomings. Feedback welcome...
A new approach towards agile and xp software development methodologyPatanjali Kashyap
The document discusses a proposed new software development methodology that incorporates holistic intelligence factors. It considers emotional (EQ), social (SQ), and moral (MQ) intelligence in addition to technical skills. The methodology would develop an organizational behavioral database to match employees' strengths and weaknesses to projects based on intelligence parameters and histories. This aims to improve overall efficiency and productivity by selecting the right people for each job.
Audrys Kažukauskas - Introduction into Extreme ProgrammingAgile Lietuva
Extreme Programming might not be a silver bullet, but in software development it is almost that. Managers get all the bells and whistles you would expect from an agile process, whilst developers are equipped with a set of principles and practices, which almost inevitably improve the codebase and enable frequent delivery of quality software. In fact, many teams, which use other software development processes (Scrum, for instance) eventually end up adopting quite a few XP practices. I'll give you an introduction into XP, share my experiences and provide references to XP material for learning more about XP.
The document provides an overview of Extreme Programming (XP), the most widely used agile development process originally proposed by Kent Beck. It discusses the key practices of XP including planning with user stories, small iterative releases, simple design practices like CRC cards, test-driven development, pair programming, continuous integration, and collective code ownership. The document notes that XP works well for projects with dynamically changing requirements, risky projects, or small development groups of up to 100 people.
Extreme Programming (XP) is an agile software development methodology that focuses on rapid delivery of working software, customer satisfaction, simplicity, communication, and feedback. Key practices of XP include having working software delivered frequently in small releases, writing automated tests before code, pairing programmers, continuous refactoring, and integrating code daily. The goal of XP is to improve productivity and quality through practices like test-driven development, simple design, pair programming, and frequent feedback from customers.
PBPK simulation as an alternative to animal testingDavid Leahy
Generic physiologically based pharmacokinetic (PBPK) models for rats and humans were developed using in vitro absorption, distribution, metabolism, and excretion (ADME) data. The models accurately predicted plasma concentrations of drugs in independent test sets, performing equally to or better than traditional allometric scaling methods. However, PBPK models have advantages over scaling in accounting for differences in drug chemistry, metabolism, and administration routes between species.
Extreme Programming (XP) is a software development methodology intended to improve quality and responsiveness to changing requirements. It involves 5 activities - planning, managing, designing, coding, and testing. Planning includes writing user stories, release planning, and frequent small releases. Managing involves dedicated workspace, stand-up meetings, and measuring velocity. Design focuses on simplicity, metaphors, CRC cards, and refactoring. Coding uses pair programming, tests first, and integration testing. All code must have unit tests that pass before release.
Extreme programming (xp) | David TzemachDavid Tzemach
It’s simply the best presentation that explains the agile methodology of Extreme Programming!
Overview
1. What is Extreme programming?
2. Extreme programming as an agile methodology.
3. The values of Extreme programming
4. The Activities of Extreme programming
5. The 12 core practices of Extreme programming
6. The roles of Extreme programming
Enjoy :)
Extreme Programming (XP) is an agile software development methodology that values adaptability over predictability. It prescribes day-to-day practices meant to embody values like communication, simplicity, feedback, and courage. XP aims to create software that is more responsive to changing customer needs through practices like pair programming, test-driven development, and frequent small releases. The XP life cycle involves short iterative planning, designing, coding, testing, and listening phases to incorporate frequent customer feedback.
This document provides an overview of Extreme Programming (XP), an agile software development methodology. It discusses XP's history and features, which include short 2-week development cycles, pair programming, test-driven development, and frequent refactoring. The core principles of XP are also examined, such as incremental planning, small releases, simple design, and sustainable pace. Various phases of the XP process are outlined, from exploration to productionizing. Requirements are captured as scenarios and prioritized by the customer. Automated testing is a key practice in XP. Both advantages like collective code ownership and disadvantages like its unsuitability for large projects are noted.
This document discusses best practices for determining blood alcohol concentration (BAC) at specific time points using ante-mortem alcohol pharmacokinetic modeling and post-mortem considerations. It describes how human alcohol metabolism works and factors that influence BAC levels over time. It also evaluates approaches for modeling ante-mortem BAC levels using the Widmark equation and discusses factors that affect post-mortem BAC measurements. The goal is to standardize the determination of BAC levels before and after death to accurately assess impairment.
The document summarizes a study that evaluated the BACTcontrol biosensor for measuring water quality. The biosensor detects the activity of alkaline phosphatase (ALP) enzyme produced by aquatic microbes. The study found strong correlations between ALP measurements from BACTcontrol and other standard analyses like cell counts, ATP levels, and microscopy within similar water types. However, correlations were lower when comparing different water types, which likely have different chemical and biological compositions. The biosensor could provide early alarms to trigger water sampling for further laboratory analysis when environmental changes are detected.
This document discusses fluid and electrolyte management in adult parenteral nutrition. It provides guidelines for water and electrolyte requirements, units of measurement used for IV fluids, normal laboratory values, and factors that influence fluid balance such as sodium levels, osmolarity, and volume status. The roles of water, sodium, and other electrolytes are explained, along with how to assess and treat volume deficits, excesses, and abnormal sodium concentrations. Clinical situations where water and electrolytes may need adjustment in PN are also covered.
Analytical Monitoring Of Alcoholic Fermentation Using NIR SpectroscopyRichard Hogue
This document discusses using near infrared (NIR) spectroscopy to develop calibration models for monitoring various parameters during alcoholic fermentation by Saccharomyces cerevisiae yeasts. Samples were obtained from fermentation runs and prepared in the laboratory to span relevant concentration ranges. Reference methods were used to determine glucose, ethanol, biomass, glycerol, and acidity levels. Partial least squares models were developed using NIR spectra and reference values. The models effectively predicted glucose, ethanol, and biomass concentrations and allowed real-time monitoring of fermentation progress.
This article describes the development and validation of a selective, sensitive, and fast high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of atorvastatin and its two metabolites, ortho-hydroxy atorvastatin and para-hydroxy atorvastatin, from human plasma. The analytes were extracted from plasma via solid phase extraction and separated using HPLC with mass spectrometric detection. The method was fully validated and demonstrated good linearity, accuracy, precision, selectivity, sensitivity with a lower limit of quantification of 0.05 ng/mL, and short run time of 3.2 minutes. The method was successfully applied to analyze samples from a clinical pharmac
Physics 2G03 Final Project Nurefsan Davulcu 1324037Nurefsan Davulcu
1) The document describes a pharmacokinetic model for alcohol metabolism. It compares the model to experimental data from previous studies.
2) The model calculates blood alcohol concentration (BAC) over time based on parameters like gender, weight, amount of alcohol consumed, and liver function.
3) The model results matched previous models and studies, correctly predicting how factors like gender, weight, and alcohol dose affect BAC levels over time. This validated the model in representing alcohol pharmacokinetics.
Analysis of bioreactor parameters online and offlinevikash_94
The document discusses various online and offline methods for monitoring cell properties in bioreactors. Online methods discussed include spectrophotometry, fluorometry, and culture fluorescence intensity. Offline analytical methods discussed include measuring medium properties, analyzing cell population composition, analyzing proteins and RNA, and flow cytometry. In situ fluorometry is highlighted as the only continuous monitoring strategy that provides information on the biochemical or metabolic state of cells.
JBEI Research Highlights - November 2018 Irina Silva
This document discusses recent advances in x-ray hydroxyl radical footprinting at the Advanced Light Source synchrotron. It compares dose response curves and mass spectrometry results from focused and unfocused white light sources. It also describes developing "drop-on-demand" methodologies to increase sample dose while maintaining microsecond exposure times, which enables high-dose experiments while minimizing sample volume. Preliminary experiments demonstrate this approach yields high quality data. The document contributes to improving synchrotron hydroxyl radical footprinting techniques for investigating protein and nucleic acid structures.
1) The document presents a study characterizing metabolic markers of ethanol withdrawal over time using various mouse models of alcohol dependence.
2) The study found changes in respiratory quotient and energy expenditure during long-term versus chronic withdrawal from alcohol that differed between light and dark cycles.
3) Re-administration of ethanol after chronic withdrawal reversed some of the metabolic effects, suggesting potential biomarkers for monitoring withdrawal. Future studies are proposed to further validate metabolic markers of withdrawal and treatment response in preclinical models.
The document summarizes the methods used to test local water samples for caffeine and theobromine. A LC/MS/MS instrument was used to analyze 500 ml water samples that underwent solvent extraction. No significant amounts of caffeine or its derivatives were detected in any samples. While below detection limits, caffeine may still be present at low levels.
1. Systems biology involves iterative experiments, technology development, theory, and computational modeling to understand biological systems. Metabolomics analyzes the complete set of metabolites in a system and can help reconstruct metabolic networks and identify biomarkers of disease.
2. Metabolomics experiments first stop metabolism quickly, then extract and analyze metabolites using techniques like LC-MS, GC-MS, and NMR. Data analysis methods identify differences in metabolite levels and flows between conditions.
3. Metabolic networks provide a more complex view than linear pathways and can be discovered through correlation of 'omics data and fluxomics experiments incorporating stable isotopes. Metabolomics is gaining interest in fields like functional genomics, systems biology, and disease research.
This study analyzed samples from 2,401 domestic wells across the United States for 55 volatile organic compounds (VOCs). VOCs were detected in 65% of samples, with mixtures of two or more VOCs found in 34% of wells. While only 1.2% of samples exceeded legal limits, the findings suggest domestic wells may be vulnerable to VOC contamination from both natural and human-caused sources. More research is needed to understand VOC mixtures and the effectiveness of in-home water treatment systems in removing potential health risks.
This study measured levels of PBDEs, PCBs, and OCPs in paired whole blood and serum samples from three subjects to estimate whole blood-to-serum conversion factors. The chemicals were extracted from the samples using liquid-liquid extraction and analyzed using GC-MS/MS. Conversion factors ranged from 0.46-1.96 with PBDE-47 closest to the theoretical value for complete serum partitioning. PCBs 74 and 99 had conversion factors above 1.1, indicating they partition more into cellular components than serum. Larger studies are needed to accurately quantify average population conversion factors.
1. The document describes the fluid compartments of the body, including total body water, intracellular fluid, extracellular fluid, plasma, interstitial fluid, and transcellular fluid.
2. It provides the normal percentages and volumes of each fluid compartment, as well as the ionic compositions of the intracellular and extracellular fluids.
3. Methods for measuring the volumes of different fluid compartments are outlined, including the use of indicators like deuterium oxide, inulin, radioactive isotopes, and dye. The characteristics needed for accurate measurement are also discussed.
This document summarizes research on electrospun nanofibers made of egg albumin (EA), poly(vinyl alcohol) (PVA), and tetracycline hydrochloride (TC-HCl) for drug delivery applications. The nanofibers were produced via electrospinning and characterized using SEM, FTIR, UV-vis spectroscopy, and tests of drug release kinetics, antibacterial activity, thermal properties, and mechanics. SEM showed smooth fibers of average diameter 590 nm. FTIR confirmed the effect of EA on PVA molecular chains. UV-vis indicated gradual, controlled release of TC-HCl from the fibers. Antibacterial tests matched the release results. DSC showed TC
Introduction: Carbon Monoxide (CO) is a colourless, odourless and euphoric gas produced as a result of incomplete combustion of organic materials. It could either cause morbidity or mortality depending on the concentration and duration of exposure. Aim: The aim of this study was to examine the long term effect of CO inhalation on haematological parameters.
This document discusses trend analysis and filling data gaps in hazard assessment using QSAR modeling. It provides some key lessons, including that vapor pressure correlates with rodent LC50s for some chemicals, but not all, as chemicals can have different toxicity mechanisms. QSAR uses trend analysis to evaluate mechanisms and chemical similarity based on common modes of action. It then discusses using trend analysis to model boiling points and toxicity values, with examples of ordering chemicals by these endpoints and correlating with molecular descriptors. Current limitations discussed are predicting metabolism and long-term effects like cancer. Adverse outcome pathways are presented as a way to integrate chemistry and disease progression over time.
1) The document discusses how the structure-specific effects of alcohol in the brain depend on the ability of different brain structures to metabolize ethanol and its metabolite, acetaldehyde.
2) Local accumulation or deficiencies of these metabolites can lead to selective disturbances in brain structures and involvement in alcohol-related behaviors and alcoholism pathogenesis.
3) The enzymes that metabolize ethanol and acetaldehyde have different roles - ethanol-metabolizing enzymes produce acetaldehyde, which mediates reinforcing and toxic effects, while the acetaldehyde-metabolizing enzyme protects against excess acetaldehyde but may also initiate addiction in some brain structures.
High-throughput Miniaturized Bioreactors for Cell Culture Process Developmen...KBI Biopharma
Decreasing the timeframe for cell culture process development has been a key goal towards accelerating biopharmaceutical development. Automated Micro-scale Bioreactors (ambrTM) is an advanced micro bioreactor system with miniature single-use bioreactors with a 9-15mL working volume controlled by an automated workstation. This system was compared to conventional bioreactor systems in terms of its performance for the production of a monoclonal antibody and a non-antibody molecule in recombinant Chinese Hamster Ovary (CHO) cell lines.
The miniaturized bioreactor system was found to produce cell culture profiles that matched across scales to 3L, 15L and 200L stirred tank bioreactors. Moreover, changes to important process parameters in ambrTM resulted in predictable cell growth, viability and titer changes, which were in good agreement to historical data from the larger scales. ambrTM was found to successfully reproduce variations in temperature, dissolved oxygen and pH conditions similar to the larger bioreactor systems. Additionally, the miniature bioreactors were found to react well to perturbations in pH and dissolved oxygen through adjustments to the PID control loop. Overall, the studies demonstrate the utility of the ambrTM system as a high throughput system for cell culture process development.
1) NMR spectroscopy was used to analyze samples taken throughout the brewing process from mash to bottling to gain insights into chemical changes. During mashing, carbohydrates like malto-oligosaccharides increased while lactic acid surprisingly increased, possibly due to bacteria.
2) During boiling, no significant changes were observed but compounds like kojibiose could serve as quality indicators. Fermentation saw increases in ethanol, acids and decreases in carbohydrates as expected.
3) Principal component analysis of stream samples from two batches separated the stages like mashing versus fermentation based on compounds like ethanol and sugars. Future work aims to fully characterize the process and use modeling to identify outliers.
1. Evaluation of Antemortem Ethanol Concentration PBPK Modeling Approaches
and Postmortem Ethanol Generation and Transport Considerations
Cowan, DM, JR Maskrey, ES Fung, T Woods, LM Stabryla, PK Scott
Cardno ChemRisk • 415-896-2400 • www.cardnochemrisk.com
ABSTRACT
Ethanol concentrations in biological matrices offer crucial information
regarding the level of intoxication of an individual at the time of death.
The antemortem levels of ethanol are typically calculated retrospectively
using a modeling approach from postmortem measured concentration with
little consideration regarding the change in ethanol concentration with time
after death. However, uncertainties such as body conditions, environmental
conditions surrounding the body, biological matrices, storage and analytical
methodology are associated with retrospective calculations. Therefore, the
objective of this study was to: 1) evaluate the typical relationships between
ethanol concentrations in various biological matrices, 2) compare and contrast
existing PBPK modeling approaches for determining ethanol concentrations
under normal living physiological conditions, 3) present an empirical modeling
approach for correlating postmortem ethanol concentrations with PBPK modeled
antemortem concentrations up until the time of death, and 4) describe best
practices for determining antemortem and postmortem ethanol concentrations with
a focus on potential sources of error. In order to generate an empirical modeling
approach, we evaluated existing PBPK model parameters including ADME, body
type, the Widmark Factor as well as novel factors including ethanol tolerance and
ethanol dehydrogenase level. The PBPK modeling approach also includes a novel
method for superimposition of multiple doses of ethanol consumed at various times,
and suggestions for adjusting the elimination rate based on body weight. We analyzed
available data on postmortem ethanol production and identified conditions and potential
markers for ethanol production through decomposition and putrefaction. Case studies
are provided to highlight changes in ethanol concentration in biological matrices. These
data indicate that this novel empirical model provided an accurate estimation of ethanol
concentration while minimizing potential sources of error. This study provides further
data to help standardize the process of determining ethanol concentration in the field of
forensic toxicology while minimizing uncertainties in real world cases.
INTRODUCTION
> Although ethanol use is prevalent in society and ethanol metabolism has been
studied by scientists for more than 100 years, it remains a challenge to precisely
determine blood ethanol concentration (BAC) following ethanol consumption due
individual variability in body and metabolism characteristics (e.g., age, weight,
height, body mass index, liver health, state of nourishment, state of hydration and
basal metabolic rate), variability in mass of ethanol present in beverages (beer,
wine, spirits), and the biological matrices sampled to determine the blood ethanol
concentration (e.g., blood analysis, breath analysis, etc.).
The physiological effects of ethanol ingestion follow a dose-response relationship
(Figure 1). Ethanol is a small, polar molecule, and therefore tends to accumulate
in water-rich areas of the body and does not significantly diffuse into fatty tissues.
Ethanol is eliminated from the human body by a specific metabolic pathway
(Figure 2).
The Widmark Equation was first proposed by E.M.P. Widmark in 1932, and is a
common approach used to retrospectively estimate blood ethanol concentrations
in persons who have consumed a known mass of ethanol. This equation is an
empirically based formula that takes into account both the metabolic absorption
rate constant, the elimination rate for ethanol in human bodies, and the
“Widmark Factor.”
In this evaluation, a modification to the Widmark Equation was proposed
to ensure the accurate prediction of blood ethanol concentration after the
consumption of multiple drinks over time. Specifically, superimposition of
multiple Widmark Equations was used to more accurately reflect BAC with
multiple drinks.
Precise determination of BAC at the time of death can also be challenging
because many variables must be considered (e.g., presence of a preservative,
sample storage condition, variation in sampling sites, putrefaction and
postmortem ethanol neoformation).
Furthermore, a key variable in the determination of BAC at the time of death
for postmortem blood samples is the level of contamination. Blood and other
biological matrices can be potentially contaminated with bacteria and other
agents capable of generating ethanol (mostly from glucose) through the
process of putrefaction. This contamination and neoformation of ethanol can
confound identification of BAC at time of death.
In this evaluation, a novel antemortem ethanol modeling approach is
combined with postmortem ethanol concentration analysis to generate
accurate predictions of blood ethanol concentration at time of death, thereby
optimizing and standardizing forensic approaches in real world cases.
Figure 1: Dose-dependent Responses to Ingestion of Alcohol
Figure 2: Metabolic Pathway for Elimination of Ethanol in Humans
𝐵𝐵𝐵𝐵𝐵𝐵 =
𝐴𝐴𝑖𝑖 𝑖𝑖 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖(1 − 𝑒𝑒−𝑘𝑘𝑘𝑘
)
𝑟𝑟𝑟𝑟
− ( 𝛽𝛽𝛽𝛽)
We propose superimposition of multiple Widmark Curves as an approach for determining BAC,
when variable consumption patterns over time make the standard single time point modeling
approach prone to overestimation of BAC.
Therefore, an adjustment can be made to the Widmark Equation to accurately estimate the
BAC from multiple drinks. Typical drinking doses of ethanol are often insufficient to saturate the
enzymes responsible for ethanol elimination. Assuming that the elimination rate is zero-order
with respect to the blood ethanol concentration, simple superimposition of multiple Widmark
Curves can accurately account for multiple ethanol-containing beverages consumed at different
times throughout a specific time period.
where,
BACn
= Blood ethanol concentration from the nth drink (g/L)
tn
= Time of the nth drink (hr)
The following case studies are designed to compare and contrast the standard and modified
Widmark Approaches:
𝐵𝐵𝐵𝐵𝐵𝐵𝑛𝑛 =
𝐴𝐴𝑖𝑖 𝑖𝑖 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖(1 − 𝑒𝑒−𝑘𝑘𝑡𝑡𝑛𝑛)
𝑟𝑟𝑟𝑟
− ( 𝛽𝛽𝑡𝑡𝑛𝑛)
Comparison of Approaches
In the second case study, the traditional Widmark Approach predicted a maximum BAC that
was 1.5 times larger than the maximum BAC predicted by the modified approach that accounts
for drinks consumed at various times.
Also, the time required to reach the maximum BAC is 22% shorter in the original approach.
In forensic investigations, the difference between the maxima can be very significant if the
traditional Widmark Approach predicts a maximum BAC above legal limits while the modified
superimposition approach predicts a maximum BAC below legal limits.
The Widmark Approach is used in many forensic ethanol-related investigations. It is therefore
important to combine an understanding of the differences in blood ethanol concentration that
are achieved due to gender, weight, height, age, BMI and other body factors, which are well-
described in the literature, with a modified modeling approach based on variable drinking
patterns as illustrated by Figure 4.
Postmortem Ethanol Generation
A number of biological matrices including blood, vitreous humor, hair, muscle, urine and
internal organs are sampled forensically to determine level of ethanol intoxication and cause
of death. Blood, vitreous humor and urine are the three most common biological matrices for
determination of BAC.
Of these three matrices, the vitreous humor is often cited as the least prone to microbial
contamination because of its biological remoteness in the human body. However, microbial
contamination of the VH may result from significant head/eye trauma. The vitreous ethanol
concentration (VAC) to BAC ratio generated provides valuable information regarding the
ethanol metabolic state in the individual, especially in forensic-related cases.
A VAC:BAC ratio of less than one implies that the individual was in the absorption phase
prior to equilibrium; a ratio greater than one implies that the elimination phase is reached.
Deviation from typical VAC:BAC ratios may suggest ethanol consumption or production by
microorganisms.
However, authors of some studies have concluded that the VAC:BAC ratio is unreliable for
determination of the source of ethanol. A literature survey of postmortem VAC:BAC ratios
presented in Table 2 provide a frame of reference for the ethanol metabolic state.
Postmortem neoformation of ethanol by microorganisms often complicates findings from
biological matrices. At least 58 species of bacteria, 17 species of yeast and 24 species of
molds is capable of producing ethanol from glucose. Information on 19 species relevant to
postmortem ethanol generation in human bodies is presented in Table 3.
Presence of microorganisms in samples with detectable ethanol concentration but no evidence
of ethanol consumption suggests postmortem production as the potential source of ethanol.
Findings from this table suggest that sample handling, storage conditions and time between
death and analysis contribute to the potential for postmortem neoformation of ethanol
production. Additionally, various biological indicators of putrefaction were identified, including
other short-chain ethanols such as n-propanol, methanol and isopropanol.
The combination of these indicators can be used to quantitatively determine the ethanol
concentration generated by microbes with considerable reliability.
DISCUSSION
The Widmark Approach is a relatively accurate approach for determination of BAC as a
function of time for an individual, provided that adjustments are made for ethnicity, body mass
index, age and individual metabolic rate. Adjustments for these factors are well described in the
literature, yet few forensic investigators have used all of them together. Lastly, superimposition
of multiple Widmark BAC curves is a reasonable method for estimation of BAC over time for
a person who consumed multiple ethanol-containing beverages at different times, and this
approach results in a more precise estimate of maximum BAC and the time to maximum BAC
than assuming all drinks were consumed at once.
Understanding the differences between absorption phase versus elimination phase of ethanol
metabolism is crucial.
During the absorption phase, equilibrium is not reached and the blood ethanol concentration
may not fully reflect the state of intoxication of the individual. Whereas in the elimination phase,
equilibrium is reached, therefore better reflecting the influence of ethanol on the individual.
When a determined VAC:BAC ratio deviates from the predicted ratios and the general
ethanol metabolism timeline, it suggests the potential for postmortem ethanol consumption or
production.
It is commonly assumed that the source of ethanol found in postmortem biological matrices
originates from the consumption of ethanol; however, a lesser known phenomenon suggest
that ethanol may also be a result of postmortem ethanol production by microorganisms.
Key indicators or biomarkers of postmortem neoformation of ethanol from the processes of
putrefaction include: n-propanol, methanol and isopropanol. Concentration of these indicators
can be used to quantitatively estimate the concentration of ethanol produced; however, this
may be limited by laboratory techniques. Other biomarkers of postmortem formation of ethanol
include: 1-propanol, 2-propanol, sec-butanol, isoamyl alcohol, isobutanol, isopentanol, diethyl
ether, acetaldehyde, formaldehyde, phenylethanol and p-hydroxyphenylethanol.
Taken together, these findings will allow for a more accurate estimation of the ethanol
concentration at the time of death.
Combination of the modified Widmark Approach for estimation of BAC prior to death with
modeling considerations for postmortem generation allows for a more accurate estimation of
the true BAC at the time of death.
REFERENCES
Available upon request
Table 1: Explanation of Widmark Equation Parameters and Example Values for
Each Parameter
Figure 3: Comparison of 6 ft, 70 kg, 30 year old Male with 5.5 ft, 55 kg, 30 year old Female BAC% Responses to One Shot of 80-proof Liquor
Figure 4: Comparison of BAC% for a 6 ft, 70 kg, 30 year old Male Consuming Three Shots of 80 Proof Liquor by Two Different Drinking Patterns
Table 2: Reported vitreous and blood alcohol ratios
Table 3: Ethanol produced by microorganisms in biological matrices
METHODS
A comprehensive literature search was performed using Pubmed, Elsevier and Google scholar to
identify published studies that have evaluated:
Relationships between ethanol concentrations in various biological matrices
PBPK modeling of ethanol concentrations and the dependence of ethanol concentration on
gender, body weight, body mass index (BMI), height, age, ethnicity, elimination rate, absorption
rate and dependence on ethanol
Evidence of putrefaction and postmortem ethanol generation by various species of
microorganism
The reliability of methods used to determine ethanol concentration in postmortem samples
Based on these findings, we propose an adjusted empirical model to accurately estimate the blood
ethanol concentration following ethanol consumption and a novel approach to understand the
confounding factors that affect postmortem blood ethanol concentration.
RESULTS
Antemortem Ethanol Concentration PBPK Modeling
The standard Widmark Equation for calculating BAC is described below and parameters
affecting the Widmark Equation are presented in Table 1.
Where:
BAC = Blood ethanol concentration resulting from the drink (g/L)
Aingested
= Mass of ethanol contained in the drink (g)
r = Widmark Factor (unitless)
W = body weight (kg)
k = absorption rate constant (hr-1
)
t = Time since the drink (hr)
ß = Elimination rate [(g/L)/hr]
Case Study #1: The Standard Approach (Figure 3)
To illustrate the differences in blood ethanol concentration (BAC) predicted by the Widmark
Equation between genders, a hypothetical case study was created where a 6 ft, 70 kg male
and a 5.5 ft, 55 kg female both drink one shot (1.5 oz) of 80-proof liquor. The Widmark
Approach was applied to estimating the BAC of these two individuals over a 90 minute time
period. All four Widmark Factor estimation approaches presented in Table 1 were applied,
and the values were averaged to determine the Widmark Factor used. The absorption rate
constant was set equal to 5 hr-1
for both individuals. Elimination rates were 0.162 g/L/h for the
male and 0.179 g/L/h for the female. Figure 3 gives the estimated BAC of the two individuals,
which shows that the female reaches a maximum BAC of 0.027% while the male only reaches
a maximum BAC of 0.016%, which is only 57% of the female maximum concentration. Also, the
male in this case reaches the maximum concentration at 24 minutes, while the female reaches
the maximum concentration at 26 minutes, which showcases the gender-specific differences in
elimination rates and Widmark Factors.
Case Study #2: The Modified Widmark Approach (Figure 4)
Based on this approach, a second hypothetical case study was created to illustrate the more
precise BAC estimation over time by superimposition of multiple Widmark Curves. In this case
study, a 6 ft, 70 kg, 30 year old male consumes three shots (1.5 oz) of 80-proof liquor over a
45 minute period. The man’s BAC was modeled for 90 minutes. One model was run assuming
that all three shots were consumed immediately at the start of the drinking period (using the
traditional Widmark Approach), and the other model was run assuming that one shot was
consumed every 15 minutes (using the modified Widmark Approach). Figure 4 compares the
results of the two modeling approaches. The instantaneous drinking approach resulted in a
maximum BAC of 0.064% at 36 minutes after the first drink, while the time-spread drinking
approach resulted in a maximum of 0.043% at 44 minutes after the first drink. Also note that the
spread out approach results in a faster decline of BAC in the 60 – 90 minute time range than
the immediate consumption approach does.