bluuebunny/crossref_metadata_2025 huggingface dataset:
Random Variable
Authors: Asmussen Søren
Published: September 2006

In intuitive terms, a random variable (r.v.)
X
is a number, whose value is determined by random factors (chance). For example, the exchange rate Euro/USD next New Year or the number of car accidents in a certain month and county.

In the car accident example, the month may be in the past or in the future. In the first case,
X
is then completely known, say
X
 = 738, and rather than as a r.v., one speaks of 738 as the
outcome
of the r.v.
X
. The precise interpretation of such issues in terms of the axioms for probability theory is discussed.

A r.v. is usually assumed to be real‐valued,
X
 ∈ Υ, like in the above examples. However, in principle also, other sets of values are possible. The most prominent example is multivariate r.v.s,
X
 = (X
1
,…, X
d
) ∈ Υ
d
(e.g. the set of exchange rates in January,
d
 = 31), which are discussed in detail in this article.

Random variables are one of the most fundamental concepts of probability theory and treated in any elementary or intermediate textbook.
Regression Models for Data Analysis
Authors: Frees Edward W.
Published: September 2006

Regression is an applied statistical model that is widely used in the social and natural sciences. This article reviews different sets of the model assumptions, the model specification process, and what one hopes to learn from the modeling process.
Risk Classification, Pricing Aspects
Authors: Feldblum Sholom
Published: September 2006

The cost of insurance coverage depends on the attributes of the insured: males have higher mortality than females and young male drivers have higher accident rates than young female drivers. Insurance premiums are based on expected losses and vary similarly. Differentiation among risks by expected cost is termed risk classification.

Risk classification uses the characteristics of a group to set rates for its members. Certain forms of classification are prohibited in many jurisdictions, such as classification by race or ethnic group; other types of classification, such as applicant age for life insurance or type of firm for workers' compensation insurance, are commonly accepted as the proper basis for insurance rates.

A good risk classification system has several attributes, not all of which are essential. Much debate focuses on the importance of each attribute; actuaries and economists emphasize the equity and homogeneity attributes, whereas other groups may emphasize more the intuition, incentives, or social acceptability attributes.
Risk Management: An Interdisciplinary Framework
Authors: Tapiero Charles S.
Published: September 2006

Risk management is shown to be based on both theory and practice. It is shown to be conceptual and technical, blending behavioral psychology, financial economics, and decision‐making under uncertainty into a coherent whole that justifies the selection of risky choices. Its applications are broadly distributed across many areas and fields of interest. The examples treated here have focused on both finance and insurance and on a few problems in industrial management.
Robustness
Authors: Hubert Mia , Rousseeuw Peter J. , Van Aelst Stefan
Published: September 2006

When applying a statistical method in practice, it often occurs that some observations deviate from the usual assumptions. However, many classical methods are sensitive to outliers. The goal of robust statistics is to develop methods that arerobust against the possibility that one or several unannounced outliers may occur anywhere in the data.
Ruin Theory
Authors: Lin X. Sheldon
Published: September 2006

This article reviews the classical results and some recent developments in ruin theory. The ruin probability and distributional properties of the time of ruin, the surplus before ruin, and the deficit at ruin are discussed for the compound Poisson risk process. A brief literature review on extensions of the compound Poisson risk process is given.
Self‐Insurance
Authors: Wade Roger
Published: September 2006

A description of various types of self‐insurance and the actuarial processes frequently associated with self‐insured programs.
Sickness Insurance
Authors: Szuch William
Published: September 2006

This article examines the meaning of sickness insurance from individual products through social health schemes.
Stochastic Simulation
Authors: Bølviken Erik
Published: September 2006

Stochastic simulation is reviewed with its main areas of application in insurance, finance and economics and its principal techniques of implementation. An extensive list of references into many fields is provided.
Social Security
Authors: Eriksen Tor
Published: September 2006

Social security is a concept that can be interpreted in many different ways and should therefore be used with the utmost caution.

Barr notes that in the United States, it refers to retirement pensions; in the United Kingdom, it refers to the entire system of cash benefits; and in mainland Europe (in accordance with the practice of the International Labor Organization), it refers to all cash benefits plus health care.

Barr chooses to describe the security system by examining the purpose of the various cash benefits.

Universal benefits awarded on the basis of a specified event, without regard to a person's income or contribution record. Examples include family allowance and free health care.

Social assistance awarded on the basis of an income test and the occurrence of a specified event, without a contribution test.

Consequently, social security can be seen as an accumulative concept for different systems that provide economical compensation in the case of illness, unemployment, old age, and so on.
Stochastic Control Theory
Authors: Højgaard Bjarne
Published: September 2006

The theory of stochastic control deals with the problem of optimizing the behavior of stochastic processes in a dynamic way, which means that the controller at any given point in time can make new decisions based on all information, which is available to him at that time.
Stochastic Orderings
Authors: Denuit Michel , Müller Alfred
Published: September 2006

We describe the basic ideas of stochastic orders, which formally describe intuitive ideas like ‘being larger’, ‘being more variable’ or ‘being more dependent’ for risks or for portfolio of risks. We give the definitions of the most important stochastic orders like usual stochastic order, convex order, supermodular order and others, and we consider their most important properties and some applications.
Stop‐Loss Reinsurance
Authors: Rytgaard Mette M.
Published: September 2006

Stop loss is a nonproportional type of reinsurance protecting the annual result of the ceding company. Stop loss is, under certain conditions, the optimal form of reinsurance for the ceding company but not optimal to the reinsurer. Considerations to be made by the reinsurer before accepting stop‐loss covers are listed. An overview of various classes of methods to price reinsurance is given.
S
undt and
J
ewell Class of Distributions
Authors: Panjer Harry H.
Published: September 2006

This article describes the Sundt and Jewell class of distributions and the related Panjer recursions.
S
undt's Classes of Distributions
Authors: Vernic Raluca
Published: September 2006

Computing the aggregate claims distribution is generally not an easy task. Among various methods used for such computations, recursive methods have the advantage of giving accurate values with considerable savings in the computing time. The purpose of this article is to give an overview of the classes of counting distributions introduced by Sundt 8, these classes leading to recursive evaluation of the corresponding aggregate claims distributions.
Reinsurance Supervision
Authors: Boller Hans Peter , Haegin Thomas
Published: September 2006

The discussion of reinsurance regulation and supervision falls into a period where heightened regulatory vigilance and uncertainty can be observed in the entire financial services industry. It is widely accepted today, that there is a need for a globally recognized method of conducting reinsurance regulation. At the international level the ambition is to create a system of common and shared standards under which the world's reinsurers will, through mutual recognition, be able to trade globally without having to comply with the different regulatory demands of national and regional authorities. This would contribute to a more efficient and transparent global market place.
Thinned Distributions
Authors: Willmot Gordon E.
Published: September 2006

A discussion of closure under thinning is given for various discrete parametric distributions. This issue has important practical applications for loss payment analysis in the presence of a deductible.
Time Series
Authors: Franke Jürgen
Published: September 2006

A(discrete) time seriesis a sequence of dataxt,t= 1, …,N(real numbers, integer counts, vectors,…), ordered with respect to timet. It is modeled as part of the realization of a stochastic process…,X-1,X0,X1,X2, …, that is, of a sequence of random variables, which is also called a time series. In engineering applications, complex‐valued time series are of interest, but in economic, financial, and actuarial applications, the time series variables are real‐valued, which we assume from now on. We distinguish betweenunivariateandmultivariatetime series for one‐dimensionalXtand for vector‐valuedXtrespectively. For the sake of simplicity, this article considers mainly univariate time series.
Transforms
Authors: Grübel Rudolf
Published: September 2006

The use of transforms is one of the pervasive ideas in mathematics and the sciences. From a pragmatic point of view, a transformation can be regarded as a tool for simplifying an otherwise difficult operation, for example, a differential equation can be turned into a simple algebraic equation with the help of Laplace transforms. Even the formula, log(
x
·
y
) = log
x
 + log
y
, in connection with the traditional use of logarithmic tables and slide rules may be seen in this light. Transforming an object may also provide insight into its structure, for example, writing a periodic function as a superposition of sine waves. From a theoretical point of view, transforms of the type considered in this article are at the core of major mathematical theories such as harmonic analysis; they have initiated research that spans the whole range of contemporary mathematics.
Truncated Distributions
Authors: Lawless J. F.
Published: September 2006

A probability distribution for a random variable
X
is said to be truncated when some set of values in the range of
X
is excluded. This article describes truncated distributions and explicitly discusses the special cases of left truncation and right truncation.
Unit‐Linked Business
Authors: Richards Stephen
Published: September 2006

This article is about unit‐linked insurance business, including unitised with‐profits (UWP) business. The major distinguishing feature of unit‐linked business is that a separate and explicit asset account is maintained for each policy. Each policy can therefore be invested entirely independently of the others, and this investment flexibility is under the control of the policyholder, not the insurer. The value of a unit‐linked policy is directly linked to the investment performance of the unitised funds selected by the policyholder. Unlike traditional with‐profits business, there is no element of discretion for setting bonuses for pure unit‐linked business. An important consequence of this for the insurer is that expenses and charges are explicitly separated, and the simple ‘cost‐plus’ approach to managing pricing has to be abandoned in favor of profit testing.
W
ilkie Investment Model
Authors: Hardy Mary R.
Published: September 2006

The Wilkie stochastic investment model, developed by Professor Wilkie, is described fully in two papers; the original version was published in 1986 and the model was reviewed, updated, and extended in 1995. In addition, the latter paper includes much detail on the process of fitting the model and estimating the parameters. It is an excellent exposition, both comprehensive and readable. It is highly recommended for any reader who wishes to implement the Wilkie model for themselves, or to develop and fit their own model.

The Wilkie model is commonly used to simulate the joint distribution of inflation rates, bond yields, and returns on equities. The 1995 paper also extends the model to incorporate wage inflation, property yields, and exchange rates. The model has proved to be an invaluable tool for actuaries, particularly in the context of measuring and managing financial risk. In this article, we will describe fully the inflation, equity, and bond processes of the model. Before doing so, it is worth considering the historical circumstances that led to the development of the model.
Working Covers
Authors: Patrik Gary
Published: September 2006

A working cover is a very standard and prevalent form of excess‐of‐loss treaty reinsurance. Working covers provide capacity and stabilization for a ceding company's financial results. A working cover provides capacity because it allows the ceding company to write higher policy limits and yet maintain a manageable risk level. Working covers enhance competition within the insurance marketplace by providing a means by which smaller insurers can compete with larger insurers. Working covers are often large enough so that many of the pricing parameters can be estimated either directly from the exposure and claims history or by a credibility weighting of that history with more general industry information.
Zero‐Modified Frequency Distributions
Authors: Panjer Harry H.
Published: September 2006

This article examines zero modification of basic discrete distributions used as counting distributions describing the number of events such as insurance losses.
Fluorescence Imaging
Authors: Ramjiawan Bram , Jackson Michael , Mantsch Henry
Published: September 2006

A number of fluorescence imaging techniques show diagnostic promise. Imaging endogenous fluorescence has been proposed as a method for cancer diagnosis. Unfortunately, tissue autofluorescence is relatively weak and poor contrast between malignant and normal tissue is seen. Contrast may be enhanced with the addition of fluorescent materials that are selectively accumulated by malignant cells, such as fluoroscein or porphyrin derivatives. The limited penetration of light at the emission maxima of these materials restricts the use of fluorescence techniques utilizing these chromophores to superficial phenomena. However, many potential applications still exist. For example, monitoring fluorescence during surgery may allow resection margins to be clearly delineated.

Other exogenous chromophores that may have may have diagnostic utility include indocyanine green (ICG). Techniques based upon visualization of the distribution of ICG fluorescence (i.e. choroidal angiography) are already prominent in ophthalmology. ICG fluorescence imaging may also find a useful niche in monitoring of burns and transplant tissue. In addition, monitoring of vascular parameters during cardiac surgery presents exciting opportunities. For example, low oxygen levels (e.g. during bypass surgery) in the heart can result in alterations in microvascular permeability. As ICG is largely bound to serum albumin, it should not be seen in extravascular spaces in normal hearts. However, increased permeability will allow albumin to diffuse into the extravascular spaces, and diffuse fluorescence across the surface of the heart will be seen. In principle, the infusion of polymers (e.g. dextrans) of various molecular weights labeled with dyes that fluoresce at various wavelengths will allow the assessment of the porosity of capillary beds in such systems.

Immunofluorescence techniques have the potential to provide unmatched sensitivity and specificity. The unique nature of antibody–antigen interactions ensures specific delivery of the fluorophore to the site of interest. The specific interaction of labeled antibodies with antigens means that the fluorophore persists in the body for a prolonged period of time (days). Following a single injection of labeled antibody, repeated measurements on the same site over the course of hours or days allow kinetic information to be readily obtained. In principle, this means that the effect of therapeutic intervention, i.e. radiation therapy, chemotherapy, etc., can be monitored.
Fluorescence Spectroscopy In Vivo
Authors: Ramanujam Nirmala
Published: September 2006

Diagnostic techniques based on optical spectroscopy have the potential to link the biochemical and morphological properties of tissues to individual patient care. In particular, these techniques are fast, noninvasive and quantitative. Furthermore, they can be used to elucidate key tissue features, such as the cellular metabolic rate, vascularity, intravascular oxygenation and alterations in tissue morphology. These tissue features can be interpreted to shed light on a variety of clinical problems, such as precancerous and cancerous growth and atherosclerosis. The goal of this report is to review the development and application of optical spectroscopy in the ultraviolet (UV) and visible (VIS) spectral regions, as a diagnostic tool in clinical applications. A particular emphasis is placed on steady‐state, UV/VIS fluorescence spectroscopy for the detection of precancers and cancers, in vivo.
Glucose, In Vivo Assay of
Authors: Heise H.M.
Published: September 2006

In vivo glucose sensing and regulation is necessary for patients with carbohydrate metabolism disorders, particularly those caused by diabetes mellitus. Self‐monitoring of blood glucose is part of the daily routine for such patients, and the measurement of capillary blood glucose, using different enzymatic assays in combination with photometric or electrochemical detection, still remains the standard method. Research activities concentrate on developing minimally invasive and noninvasive methodologies, the latter being based on spectroscopic techniques exploiting optical glucose specific characteristics, i.e. wavelength‐dependent absorptivities and refractive indices, mainly in the near‐infrared (NIR), or the rotation of linearly polarized radiation in the visible range. Owing to the complexity of the integrally probed tissue, and the presence of many interfering compounds, only multivariate spectroscopic measurement strategies, using several wavelengths, can be used for a noninvasive in vivo assay of glucose. Further complications arise from the heterogeneous distribution of glucose in the intravascular, interstitial and intracellular space and differences in their dynamics. In contrast to the established reference methodology which uses capillary blood, especially for the hypoglycemic concentration range, the imprecision observed so far within several experimental optical approaches is regarded as unacceptable for patient self‐monitoring. Further research is needed to establish an in vivo glucose assay for diabetic patients, or for direct monitoring in intensive care units and operating theatres, based on optical spectroscopy.
Infrared Spectroscopy in Clinical and Diagnostic Analysis
Authors: Shaw R. Anthony , Mantsch Henry H.
Published: September 2006

The infrared spectrum of a mixture serves as the basis to quantitate its constituents, and a number of common clinical chemistry tests have proven to be feasible using this approach. This article reviews the infrared spectroscopy‐based analytical methods that have been developed for consideration as clinical assays, including serum analysis, urine analysis, amniotic fluid assays for the estimation of fetal lung maturity, and others. Because of the widespread interest in the potential for in vivo measurement of blood glucose using near‐infrared spectroscopy, a separate section is devoted to the analysis of glucose in whole blood.

A related technique uses the infrared spectrum of biomedical specimens directly as a diagnostic tool. For example, the spectra of serum and of synovial fluid have proven to be useful in the diagnosis of metabolic disorders and arthritis, respectively, without explicitly recovering their chemical composition from the spectra. Rather, characteristic spectral features and patterns have been identified as the basis to distinguish spectra corresponding to healthy patients from those corresponding to diseased patients. These applications are reviewed here.

Issues such as ease of use, speed, reliability, sample size, and calibration stability all play important roles in governing the practical acceptability of infrared spectroscopy‐based analytical methods. To provide a framework to illustrate these issues, descriptions are included for the various procedures that have been explored to wed successfully infrared spectroscopy to clinical chemistry.
Infrared Spectroscopy, Ex Vivo Tissue Analysis by
Authors: Jackson Michael , Mantsch Henry H.
Published: September 2006

Infrared (IR) spectroscopy provides information relating to the vibration of covalent bonds within molecules. The wavelength of light absorbed by a vibrating bond depends upon the atoms in the bond, the type of bond, the type of vibration and inter‐ and intramolecular interactions. For complex samples such as human tissues an IR spectrum therefore provides a direct indication of sample biochemistry. With the correct choice of sampling methodology (usually an IR microscope) information on the biochemical nature of disease states can be obtained from tissue samples, which can often be useful diagnostically. Variations in spectral signatures arising from nucleic acids, proteins and lipids can provide important information in a number of disease states, including Alzheimer's disease (AD), breast cancer and skin cancer.

The information obtained by IR spectroscopy is difficult to obtain with many other instrumental techniques. For example the signal‐to‐noise ratio obtained by IR microscopy is far superior to that seen with Raman methods, allowing more sophisticated data processing and so more information to be extracted. Furthermore, many species of interest cannot be studied in situ with other techniques. Nucleic acids are a case in point. Powerful techniques such as nuclear magnetic resonance spectroscopy provide no information concerning this material, while Raman techniques only provide information relating to individual nucleotides. In contrast, DNA and RNA give rise to IR signatures that provide information relating to nucleic acid content/structure.

To appreciate fully the information contained in the complex spectra obtained from human tissues and cells, a unique combination of expertise in spectroscopy, biochemistry and anatomy/histology is required. This combination allows the investigator to avoid potential artefacts due to incorrect sampling and spatial variations in sample composition and to attribute the major absorptions present in spectra to individual biochemical species. However, spectral interpretation is often a highly subjective process, a fact that is made worse when one considers that many thousands of spectra are often acquired from a single tissue section. The application of pattern recognition techniques to IR data removes this subjectivity and allows realistic processing of these large data sets. In addition, many new methods are being developed which allow presentation of these complex data sets in a form readily interpreted by the nonexpert.
Magnetic Resonance in Medicine, High Resolution Ex Vivo
Authors: Smith Ian C. , Blandford Dorothea E.
Published: September 2006

Nuclear magnetic resonance (NMR) spectroscopy, or magnetic resonance spectroscopy (MRS), is a powerful physical technique to determine the quantity and structure of chemical compounds in a specimen. It involves the interaction of radiofrequency (RF) electromagnetic radiation with a collection of nuclei immersed in a strong magnetic field. It is unique in its ability to provide nondestructive chemical analyses in vivo and in vitro. Moreover, no or very little pretreatment of the specimen is required prior to making a measurement. Spectra take only a few minutes to acquire, and it is not necessary to preselect the metabolites of interest in order to detect and quantify them. Its limitations are a lack of availability of instruments and large databases of spectral changes correlated with pathological conditions, and a detection sensitivity of approximately 1 µM.
Near‐Infrared Spectroscopy, In Vivo Tissue Analysis by
Authors: Sowa Michael G. , Leonardi Lorenzo , Matas Anna , Schattka Bernie J. , Hewko Mark D. , Payette Jeri R. , Mantsch Henry H.
Published: September 2006

In vivo near‐infrared (NIR) spectroscopy has the potential of becoming an important tool in a number of areas in clinical medicine. Technological developments in photonics that have been spurred on by the communication revolution have set the stage for rapid advancement of optical and NIR spectroscopy based on noninvasive or minimally invasive medical diagnostic techniques. The goal of this article is to review the current capabilities and limitations of in vivo NIR spectroscopy and highlight the impact of these capabilities and limitations in selected areas where NIR spectroscopy is being used to address clinical problems. The optical properties of tissues are briefly reviewed, as are the instrumental methods available to the experimentalist. These properties and methods largely dictate the feasibility of an in vivo spectroscopic diagnostic approach and constrain the scope of problems that can be tackled using optical–NIR spectroscopy. Some of the more successful applications are described, including studies of tissue oxygenation, ischemia, and viability. A number of factors that can confound interpretation of in vivo NIR results are discussed. The number and magnitude of confounding influences that arise in in vivo spectroscopy can be daunting to the experimentalist and may represent the largest barrier in transforming in vivo spectroscopic measurements into clinically meaningful and reliable information. In vivo NIR spectroscopy abounds with opportunity and challenge.
Magnetic Resonance, General Medical
Authors: Winter Patrick , Bansal Navin
Published: September 2006

Nuclear magnetic resonance (NMR) is the basic physical phenomenon in which certain nuclei absorb and emit radiofrequency (RF) radiation while in the presence of a magnetic field. The noninvasive nature of NMR techniques, including magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), has allowed explosive developments in biomedical applications since the late 1970s. MRI of protons is now a widely accepted clinical imaging technique, whereas MRS of various nuclei, including31P,1H,13C,23Na, and19F, can provide a vast amount of metabolic and physiological information. MRI provides significant advantages over many other imaging techniques in terms of resolution, contrast, and its noninvasive nature. Although not as common in clinical medicine, MRS also provides valuable metabolic information that cannot be obtained by other techniques. This article reviews the fundamentals of spatial encoding, contrast, artifacts, and applications of MRI as well as some recent advances in the field. Some applications of biomedical MRS of various nuclei are also discussed.
Infrared Spectroscopy in Microbiology
Authors: Naumann Dieter
Published: September 2006

Infrared (IR) spectra of intact microbial cells are highly specific fingerprint‐like signatures which are used to differentiate, classify, and identify diverse microbial species and strains. Microbial IR spectra are also useful to (1) detect in situ intracellular compounds or structures such as inclusion bodies, storage materials, and endospores, (2) monitor and quantify metabolically released CO2in response to various different substrates, and (3) characterize growth‐dependent phenomena and cell–drug interactions. The characteristic information, useful for microbial characterizations, is generally distributed over the entire IR region of the electromagnetic spectrum, i.e. over the near‐infrared (NIR), mid‐infrared (MIR), and far‐infrared (FIR). The spectral traits can be systematically extracted from the typically broad and complex spectral contours applying resolution enhancement techniques, difference spectroscopy, and pattern recognition methods such as factor‐analysis and cluster‐analysis, and artificial neural networks (ANNs). Additional applications arise by means of a light microscope coupled to the IR spectrometer. IR spectra of microcolonies containing less than 103cells are obtained from colony replica by a stamping technique that transfers microcolonies growing on culture plates to a special IR‐sample holder. Using a computer‐controlledx,y‐stage together with mapping and video techniques, the fundamental tasks of microbiological analysis, namely detection, enumeration, and differentiation of microorganisms, are perspectively integrated in one single apparatus.
Mass Spectrometry in Structural Biology
Authors: Schiller Jürgen , Arnold Klaus
Published: September 2006

Mass spectrometric methods may serve as powerful analytical methods in life sciences and medicine. Mass spectrometry (MS) is comparable in sensitivity to techniques based on chromatography or electrophoresis but has superior resolution. Although there are a number of suitable ionization methods, allowing the analysis of biological molecules that are of high molecular weight and low volatility, there are mainly two “soft‐ionization” techniques that confer only a minimum of degradation of the analyte: MALDI (matrix‐assisted laser desorption/ionization) and ESI (electrospray ionization).

The following report provides a short overview on the advantages and drawbacks of MALDI analysis of biological samples. Whereas most applications of MALDI are in the field of protein analysis, the analysis of carbohydrates and lipids will also be comprehensively discussed. It will be shown that MALDI is a useful tool especially in the field of lipid analysis, whereas with carbohydrate analysis a number of problems still have to be solved. MALDI is a rapid and very sensitive (from the low picomolar to the attomolar range) tool that tolerates high amounts of impurities (in contrast to ESI), which are typically present in biological samples. A further advantage is that mainly singly charged ions are formed; this enables MALDI to be applied even to the analysis of crude mixtures. In comparison with ESI, MALDI is more sensitive and detects compounds of higher molecular weights, whereas ESI provides better mass resolution. Therefore, the combination of both methods is, in many cases, the ideal solution for a number of analytical problems.
Single Biomolecule Detection and Characterization
Authors: Greulich Karl Otto
Published: September 2006

In order to detect and analyze single biomolecules, near‐field microscopes and conventional far‐field microscopes are used. Spectroscopic experiments are now possible to test predictions of quantum mechanics in a very direct way. With biological macromolecules, chemical reactions can be seen directly in the microscope. Mechanical properties of individual macromolecules can be measured with very high precision. This allows a very basic process of life, the generation of motion, to be understood in its finest details. Finally, single molecule experiments allow the DNA molecule to be studied in its full, practically unlimited individuality.
Voltammetry In Vivo for Chemical Analysis of the Living Brain
Authors: O'Neill Robert D. , Lowry John P.
Published: September 2006

The mammalian brain is the most complex structure known to science. Our behavior, feelings, thoughts, and maybe even consciousness itself, may be a reflection of the interplay of electrical and chemical signaling that create these states, and how the physical brain gives rise to the properties of mind remains a major unanswered question. It is clear, however, that many of the drugs used empirically in the treatment of neurological disorders, such as Parkinson's disease, schizophrenia and depression, as well as mind‐altering substances of abuse, have specific chemical actions on nerve cells in the brain, highlighting the importance of chemical signaling in the functioning of neural networks.

A growing number of methodologies are being developed, including sampling, spectroscopic and electrochemical, to study neurochemical phenomena in the living brain. One such set of techniques focuses on the detection of substances released from nerve cells, using amperometric electrodes and voltammetry in vivo (VIV) techniques. By implanting a microvoltametric electrode in a specific brain region, applying a suitable potential profile and recording the resulting faradaic current, changes in the concentration of a variety of substances in the extracellular fluid (ECF) can be monitored with sub‐second time resolution over extended periods. This allows investigations of the functions and roles of specific neurochemicals in neuronal signaling, drug actions, and well‐defined behaviors. The main limitations associated with VIV is, on the one hand, the limited number of ECF species that are electroactive, and on the other, the fact that electroactive substances present tend to oxidize at similar potentials, interfering with each other's detection. These restrictions are being overcome by ongoing developments, including the design of biosensors to broaden the range of target analytes and permselective membranes to block interference.
Glycolipid Analysis
Authors: Morrison Ian M.
Published: September 2006

Glycolipids are conjugated macromolecules that have a carbohydrate (oligosaccharide) component covalently bound to a lipid (diacylglycerol, ceramide, sterol or polyprenol) component. They are present both in procaryotes and eucaryotes but the carbohydrate components, as well as the lipid components, vary considerably between different animal, plant and microbial cells. The biological specificity of a glycolipid is due mainly to the carbohydrate structure. The amphipathic nature of glycolipids means that a single extraction scheme is impractical for all the different molecular species while special techniques are required to differentiate between the neutral glycolipids and acidic glycolipids (gangliosides). Thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC) are the major purification methods. Chemical methods are used to determine the carbohydrate and lipid profiles as well as the linkage analysis of both types of components and are used in conjunction with gas chromatography (GC), HPLC and TLC, sometimes coupled with mass spectroscopy (MS). Enzymatic methods can be used to determine the linkage sequence and anomeric configurations of the oligosaccharide structures and the same parameters are being determined by immunological methods with increasing frequency. Enzymatic methods are also used to establish the linkage analysis of the fatty acid in the diacylglycerol species. However, various MS and both
1
H‐ and
13
C‐NMR (nuclear magnetic resonance) methods, but mostly the former, are now invariably used to confirm the full structural features of an unknown glycolipid. The type of MS method used, matrix‐assisted laser desorption/ionization (MALDI), fast atom bombardment (FAB) or tandem mass spectrometry (MS/MS) will depend on the type of glycolipid.
Monosaccharides and Sugar Alcohol Analysis
Authors: Sturgeon Robert J.
Published: September 2006

Carbohydrates, including monosaccharides and sugar alcohols, are widely distributed in nature, being found in plants, animals and micro‐organisms. They occur free, or in glycosidic linkage as polysaccharides or glycoconjugates (glycoproteins and glycolipids). It is important that suitable and sensitive methods are available for the analysis of these sugars, as in many cases only very small (microgram) amounts of material may be available. Polysaccharides and glycoconjugates must first be depolymerized to produce the monosaccharides quantitatively. The total carbohydrate released in these reactions may be determined by spectrophotometric or enzymic procedures.

Numerous separation and detection methods are available to measure the individual sugar components. Paper and thin‐layer chromatography were two of the earliest techniques available, giving mainly qualitative values for individual sugar components. Major advances were made first in gas–liquid chromatography (GLC) and then with various types of liquid chromatography (LC) in the separation of individual sugars.

High‐performance liquid chromatography (HPLC) and capillary electrophoresis (CE) are now two of the most commonly used techniques in sugar chromatography. Highly sophisticated detection systems, such as mass spectrometry (MS) for gas–liquid chromatographic separations, and spectrophotometric, fluorometric and electrochemical detection systems for LC of carbohydrates with suitable chromophores or fluorophores have been developed.

Carbohydrates have been derivatized for use either in precolumn or postcolumn chromatography, resulting in the detection limit in the most sensitive systems approaching yoctomole levels for individual sugars.
Proteoglycan and Acidic Polysaccharide Analysis
Authors: Lauder Robert M.
Published: September 2006

The isolation and analysis of proteoglycans (PGs) and the acidic polysaccharide glycosaminoglycan (GAG) chains attached to them is an area of increasing importance. PGs are a structurally diverse group of complex macromolecules comprising a core protein, varying in size from 11 to 400 kDa, to which are attached one or more GAG chains of the same or a different type. These chains carry a negative charge derived mainly from sulfate groups and are composed of a repeating disaccharide, a hexosamine and either a hexuronic acid or, in keratan sulfate (KS), galactose.
Capillary Electrophoresis in Detection of Chemicals Related to the Chemical Weapons Convention
Authors: Boulet Camille A.
Published: September 2006

This article describes the application of capillary electrophoresis (CE) to the analysis of compounds relevant to the Chemical Weapons Convention (CWC). CE is an analytical technique that employs narrow‐bore, fused‐silica capillaries to perform high‐efficiency separations of analytes based on their mobilities in an electric field. In CE, analytes are dissolved in a buffer solution and placed in a capillary to which an electric field is applied. The analytes then migrate at a rate determined by their charge and size and are detected as they migrate past a detector. CE can analyze a broad range of compounds and is particularly applicable to the analysis of water‐soluble degradation products of scheduled compounds under the CWC. Compounds typically analyzed by CE include the hydrolysis products of nerve agents such as the alkylphosphonates and hydrolytic or oxidative products of the sulfur mustards such as thiodiglycol. The alkyphosphonates require the use of indirect ultraviolet (UV) detection or other detection methods as they do not possess a suitable UV chromophore. Degradation products of the sulfur mustards have been analyzed by micellar electrokinetic chromatography (MEKC) and direct UV detection. The ability of CE to analyze anionic, cationic, zwitterionic, and neutral CWC‐related compounds, whether they be chemical warfare (CW) degradation products or scheduled starting materials, without the requirement for elaborate sample processing or labeling procedures, is an important demonstration of the utility of CE for the analysis of CWC‐related compounds. CE can be an important screening method for rapid sample processing and further analysis for unambiguous identification. The relative ease of analysis should also increase its utility in field and on‐site analysis where minimizing the logistic burden is attractive.
Gas Chromatography/Mass Spectrometry in Analysis of Chemicals Related to the Chemical Weapons Convention
Authors: Wils Eric R.J.
Published: September 2006

Mass spectrometry in combination with gas chromatography (GC/MS) is at present the most suitable technique for the analysis of chemicals related to the Chemical Weapons Convention (CWC), as GC/MS is capable of providing the required analytical evidence needed to sustain any claim of noncompliance under the Convention. Chemical analysis will be carried out on‐site, during an inspection using mobile GC/MS equipment, or off‐site, in at least two designated laboratories selected by the Organization for the Prohibition of Chemical Weapons (OPCW). GC/MS analysis under the Convention is focused primarily on qualitative analysis (unambiguous identification) rather than on quantitative analysis. Moreover, GC/MS analysis has to be established under a strict quality assurance/quality control (QA/QC) program. The two most applied techniques in verification analysis are low‐resolution electron impact (EI) and chemical ionization (CI) GC/MS under full scan conditions. EI is the oldest and still most used ionization technique for the analysis of CWC related chemicals. Therefore, special attention is paid in this article to the fragmentation under EI conditions of a number of chemicals belonging to the CWC Schedule list. The chemicals placed on this list are the target for the verification analysis, especially the Schedule 1 chemicals, which encompass the well‐known chemical warfare (CW) agents such as the nerve agents sarin (GB), soman (GD), tabun (GA) andO‐ethylS‐2‐diisopropylaminoethyl methylphosphonothiolate (VX) and the vesicants mustard gas (HD) and lewisite (L). Sample preparation methods for these chemicals and their degradation products in environmental, synthetic material, and biological sample matrices are described in this article.
Nuclear Magnetic Resonance Spectroscopy in Analysis of Chemicals Related to the Chemical Weapons Convention
Authors: Mesilaakso Markku , Niederhauser Andreas
Published: September 2006

Nuclear magnetic resonance (NMR) spectroscopy is a valuable analytical technique for the identification of chemicals related to the Chemical Weapons Convention (CWC). One‐dimensional (1‐D) proton, carbon, fluorine, and phosphorus NMR spectra (
1
H,
13
C{
1
H},
19
F,
31
P{
1
H}, and
31
P spectra) (terminology:
1
H, nucleus hydrogen‐1 or proton, experiment hydrogen‐1 or proton observation;
13
C, nucleus carbon‐13;
13
C{
1
H}, experiment carbon‐13 observation with simultaneous
1
H decoupling;
19
F, nucleus fluorine‐19, experiment fluorine‐19 observation;
31
P, nucleus phosphorus‐31, experiment phosphorus‐31 observation;
31
P{
1
H}, experiment phosphorus‐31 observation with simultaneous
1
H decoupling) are recorded from test samples for use in the identification of chemicals. The NMR spectrum of a chemical is like a fingerprint. The chemical is identified on the basis of similar sample and reference spectra. In the case of an unknown chemical two‐dimensional (2‐D) spectra can assist in its structure elucidation. 2‐D NMR is also more suitable than 1‐D NMR for the analysis of mixtures.

NMR sample preparation is simple. A liquid sample can be run as such or the liquid is partially or totally changed to a deuterated solvent. Solid samples are extracted with organic or aqueous solvents for the preparation of analytical samples. The main disadvantage of NMR is the lack of separation methods and the consequent problems of sample background causing occasional resonance overlapping, especially at very low concentrations.
Sampling, Detection and Screening of Chemicals Related to the Chemical Weapons Convention
Authors: Cooper David B.
Published: September 2006

The Chemical Weapons Convention (CWC), which entered into force on April 29, 1997, prohibits the development, production, stockpiling and use of chemical weapons (CW). It is administered by the Organization for the Prohibition of Chemical Weapons (OPCW), which is based in The Hague.

During the course of inspections, whether routine or challenge, there may be a requirement for the inspection team (IT) to investigate unresolved ambiguities. The IT has the right to request clarification, and if ambiguities cannot be clarified by negotiation then samples may be taken for analysis.

Examples of sampling equipment, procedures and sample management techniques are described, together with a brief description of screening and detection. Some analyses may be performed on‐site by the inspectors, using equipment they bring with them, but for more difficult questions it may be necessary to remove a sample for analysis on an anonymous basis in two or more of a global network of laboratories “designated” by the OPCW. The end result of any sampling and analysis operation must be able to stand up to international scrutiny, and therefore chain‐of‐custody or audit‐trail procedures must be strictly followed. The process should allow the re‐creation of the position or state of the sample at any time during the handling of the sample from cradle to grave.
Gas Chromatography in Screening of Chemicals Related to the Chemical Weapons Convention
Authors: Kostiainen Olli
Published: September 2006

Various gas chromatographic methods, which are useful for the screening of Chemical Weapons Convention (CWC)‐related chemicals, are described in this section. Proper choice of columns, detectors, and injection techniques are discussed, because they are crucial to the optimization of gas chromatography (GC) as a routine tool. Also various identification methods are described. Retention index monitoring (RIM) is described in more detail than other identification methods because it is the most reliable GC technique to be used in the identification using a retention index (RI) library without the need for an authentic chemical.
Diagnostic Hematology
Authors: Hubbard J.
Published: September 2006

Hematology, in its pure form, is the study of the red blood cells (RBCs), white blood cells (WBCs), and platelets during normal and pathological conditions. Quantitative and qualitative evaluation and interpretation of the formed elements of the blood require a whole blood sample to be counted using automated cell counters based on electrical impedance or laser light scatter techniques. A wide range of disease types can be encountered, such as hereditary, nutritional, metabolic, traumatic, infections and inflammatory conditions, and hormonal, immunological and neoplastic disorders. All these disorders can result in changes to the blood cell profile, which can be used to aid in diagnosis. Most important to the diagnosis of hematological diseases is an in‐depth understanding of the different causes of anemia and the pathogenesis of the leukemias.
Electroanalytical Chemistry in Clinical Analysis
Authors: Su Evangeline Y. , Bocarsly Andrew B.
Published: September 2006

Clinical electrochemistry has historically been limited to the detection of blood gases, physiological pH, and alkali metal cations using ion‐selective electrodes (ISEs). In recent years, current flow techniques have been introduced allowing for the detection and quantification of a variety of proteins and metabolites. Key to this type of analysis is the development of an electrode interface which is both catalytic and selective for the analyte of interest. To this end, a wide variety of chemically modified electrode (CME) interfaces have been developed. Such interfaces are often based on the interaction of a redox enzyme with the analyte of interest. In addition, interfaces composed of immunospecific elements or size specific elements have been examined as selective electrode surfaces.