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Negotiating your contract: points to consider.

The CAP offers two publications that contain basic contractual information. One was distributed in March 1983, and the other is being revised at this time to reflect recent developments. This article reviews some of the changes in contract concerns and opportunities, and serves as an interim source of information that may assist pathologists in their negotiations.

Contract Services↗

Plasmodium vivax polymorphs and Plasmodium falciparum circumsporozoite proteins in Anopheles (Diptera: Culicidae) from Belize, Central America.

Eight species of Anopheles mosquitoes from indoor/outdoor human landing collections in Belize, Central America, were examined for human Plasmodium circumsporozoite protein (CSP) using an enzyme-linked immunosorbent assay (ELISA). A total of 14 of 9,104 females tested were positive from general surveys throughout Belize and three of 11,966 were positive from a longitudinal study in Caledonia, northern Belize. ELISA results, using pooled head-thorax preparations and species-specific monoclonal antibodies directed against the circumsporozoite proteins of Plasmodium falciparum and two Plasmodium vivax polymorphs (210 and VK247), found four species reactive: Anopheles vestitipennis (3 pools), Anopheles darlingi (2 pools), Anopheles albimanus (10 pools), and Anopheles gabaldoni (2 pools). The minimum field infection rates (MFIR) for combined Plasmodium species from the general survey were 0.282% for An. vestitipennis, 0.271% for An. darlingi, 0.126% for An. albimanus, and 0.395% for An. gabaldoni. MFIRs for combined Plasmodium species from the longitudinal study in the village of Caledonia were 0.018% for both An. vestitipennis and An. albimanus and 1.66% for An. gabaldoni. Positive CSP pools were collected from the Cayo, Corozal, Orange Walk, Stann Creek, and Toledo political districts. No CSP positive pools were detected from collections in the Belize District. The study provides valuable information on the spatial distribution and species type of Plasmodium positive mosquitoes. This information, in combination with other vector data, suggest that An. vestitipennis and An. darlingi are commonly involved in malaria transmission. Additionally, these species appear to be much more efficient vectors than An. albimanus in Belize.

Animals↗

Heterogeneity of monoclonal antibody distribution and radiation dose in tumors: a modeling analysis.

For successful use of monoclonal antibodies and their conjugates for diagnosis and therapy, it is helpful to understand both macroscopic and microscopic aspects of antibody distribution. Antibody distribution in a tumor is simulated by splicing together information on global pharmacokinetics, transport across the capillary wall, diffusive penetration through the tumor interstitial space, and antigen-antibody interaction. One interesting implication of this simulation is a microscopic dosimetry for radioimmunotherapy. The information of microscopic radioconjugate distribution will enable us to calculate absorbed dose in a tumor at the microscopic scale. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after intravenous (bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for I-131 are used to explore the effect of affinity on the antibody distribution and consequent absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule and for a cubic lattice of such nodules. This modeling analysis demonstrates that 1) antigen-antibody binding in tumors can retard antibody percolation; 2) high antibody affinity at a given dose tends to decrease antibody percolation and result in a heterogeneous distribution; 3) heterogeneous antibody distribution results in heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule or small tumors. PERC and PERC-RAD, the computer program packages developed for these analyses, provide a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of immunoconjugates (PERC) and the consequent absorbed radiation dose in tumors (PERC-RAD). This mathematical model and the general principles developed here can be applied as well as to other biological ligands and beta-emitters.

Antibodies, Monoclonal↗

Flow cytofluorimetric determination of protein distribution throughout the cell cycle.

Quantitative treatment of multiparametric determination on cells using flow cytofluorometry was made possible by the development of a computer program that allows the relative quantification of a specific protein as a function of the position of cells during the cell cycle. This type of analysis provides interesting information about the distribution of a given protein throughout the cell cycle. Four examples showing the distribution of specific proteins illustrate such a quantification during the cell cycle in two different cell lines. The program also allows for the handling of a series of histograms obtained by the analysis of protein distribution as a function of DNA content in relation to a third parameter. To illustrate possible applications for this program, the evolution of the distribution of two proteins, the oncoprotein p53 and the histone H1(0), during the induced differentiation of murine erythroleukemia cells has been studied.

Animals↗

Monitoring mortality in general practice in Grampian, Scotland.

Information on the distribution of mortality and morbidity in general practice is scarce, and not easily accessible either by health authorities or individual general practices. Although the assessment of population mortality is a standard public health measure, colleagues in public health, information sciences and general practice rarely undertake such activity related to general practice populations. Mortality information can be used for various purposes. Examples are providing background data for clinical audits or alerting practitioners to quality issues in the healthcare industry or even suggesting environmental hazards. We measured the experience of mortality in all generally practices in Grampian in the years 1991 to 1999. All practices were notified of their actual and expected mortality over this period of time and asked for comment. Only three general practices had excess mortality experience in both the periods 1991 to 1995 and 1996 to 1999. Only a minority of practices commented on the results. It appears that a high presence of nursing homes in a practice might skew the results; this phenomenon will be central to further inquiry. Future methodology for recording death in general practice should take account of this, as well as providing an account of the qualitative aspects of patients' need for a dignified satisfactory death.

Adolescent↗

Velocity imaging by rapid cycle tagging.

The unique abilities of magnetic resonance imaging (MRI) to provide detailed images of blood flow in the body, and without resorting to the injection of contrast agents, has provided the stimulus for the keen interest in this subject. In this paper we discuss a technique aimed at providing quantitative information on the distribution of velocity of blood flow across the lumen of a vessel. The technique is designed to reduce the signal from stationary material allowing for a much more accurate determination of the signal from moving material. A particular feature is that the physical phenomenon sensitized is time-of-flight displacements or "fresh spin inflow," and the technique does not rely upon phase-sensitive modulations. Further this technique produces a steady-state spatial distribution of magnetization, and hence a signal, which reflects both the time at which material enters the selected slice and how long the material remains in the slice. In this way, a single image will provide the information necessary to extract information on the velocities of interest.

Blood Flow Velocity↗

Distribution and characterization of [3H]mesulergine binding in human brain postmortem.

Much interest is currently being directed towards serotonin (5-HT) receptors of type 2C (5-HT2C) because of their possible involvement in the control of different activities, such as the composition of the cerebrospinal fluid, locomotion, feeding, neuronal excitability and anxiety. The limited information regarding their distribution in the human brain prompted us to investigate, and to characterize the binding of [3H]mesulergine, a HT2C antagonist, in autopsy samples from 24 subjects. The results showed that the [3H]mesulergine binding represented 95% of the total binding and equilibrium saturation binding experiments resulted in a single straight line, consistent with the presence of one site only. The area with the highest density of [3H]mesulergine binding was the choroid plexus, followed at a significantly lower level by the hippocampus, substantia nigra, basal ganglia, amygdala, hypothalamus and prefrontal cortex. The pharmacological profile of the [3H]mesulergine binding was consistent with that of 5-HT2C receptors, since the most effective displacers were ritanserin, mesulergine and mianserine, followed by clozapine, ketanserine and m-CPP, while other compounds had a negligible or no effect. These findings, showing a wide distribution of [3H]mesulergine binding sites in the human brain, could provide anatomical bases for the different functions attributable to 5-HT2C receptors in humans.

Adult↗

Autoradiographic distribution of 14C-labeled 3H-imidazo[4,5-f]quinoline-2-amines in mice.

The highly mutagenic heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), are formed during heating of protein-rich foods. In order to gain information about the distribution and fate of IQ and MeIQ in vivo, a whole-body autoradiographic study of i.v.-injected 14C-labeled IQ and MeIQ has been performed in male NMRI, pregnant NMRI, and female C3H mice. IQ and MeIQ showed similar distribution patterns. At short survival times, the autoradiograms were characterized by an accumulation of radioactivity in metabolic and excretory organs (liver, kidney, bile, urine, gastric and intestinal contents, salivary glands, nasal mucosa, and Harder's gland), as well as in lymphomyeloid tissues (bone marrow, thymus, spleen and lymph nodes) and in endocrine and reproductive tissues (adrenal medulla, pancreatic islets, thyroid, hypophysis, testis, epididymis, seminal vesicles, ampulla, and prostate). The liver and kidney cortex were identified as sites of retention of nonextractable radioactivity. IQ and MeIQ showed a strong affinity for melanin. IQ and MeIQ passed the placenta, but no radioactivity was retained in fetal tissues. The results pinpoint the liver as a site of IQ- and MeIQ-mediated toxicity. Future studies of IQ and MeIQ may be guided by and clarify the role of other tissue localizations in the toxicity of IQ and MeIQ.

Animals↗

Standardising and mapping open-source information for crisis regions: the case of post-conflict Iraq.

Painting an accurate picture of the situation on the ground in countries in crisis is vital for the efficiency of humanitarian aid and reconstruction agencies. This study describes a method for standardising and mapping the plethora of open-source information. The test site for the study is post-conflict Iraq. Important information on aid distribution, reconstruction and security in Iraq can be derived from the reports of humanitarian aid agencies and the media, before being formatted, inserted into a database and mapped. The product is a visual, cartographic structure of otherwise random information, showing which organisations are working in the country, which thematic and geographic areas are being prioritized in the field, and which areas most frequently experience security events. This type of mapping not only highlights the overall working environment within different parts of the country, but it may also serve as a decision-making tool for donors and humanitarian aid agencies planning to deploy personnel.

Decision Making, Organizational↗

The annulate lamellae--from obscurity to spotlight.

This review aims to provide a comprehensive and in-depth survey of a cell organelle, the annulate lamellae, that is widely distributed and especially prevalent in both female and male sex cells as well as tumor and cancer cells. The organelle is also present in many somatic cells and plant cells. Emphasis is placed on the contributions that electron microscopy and associated experimental approaches have made in providing information about the distribution, ultrastructure, morphogenesis and relationships of annulate lamellae to other cellular organelles, especially the nuclear envelope and endoplasmic reticulum, as well as cell product. An increasing number of experimental manipulations have recently been shown to alter, either increase or decrease, the amount of annulate lamellae and these studies are explored in depth. Information about the origin and morphogenesis of annulate lamellae in different cells is summarized and extensive coverage is given to several hypotheses about possible annulate lamellae function. A detailed bibliography provides a thorough compilation of research dealing with annulate lamellae. A major goal of this extensive review is to generate increased awareness of, and interest in, this cell organelle for students and investigators of the cell who, by bringing current techniques in cell and molecular biology to bear, might focus and intensify studies on the function of an organelle whose precise role in the cell is presently enigmatic.

Animals↗

Vertical distribution of ozone and nitrogenous pollutants in an air quality class I area, the San Gorgonio wilderness, southern California.

Information about spatial and temporal distribution of air pollutants is essential for better understanding of environmental stresses affecting forests and estimation of potential risks associated with air pollutants. Ozone and nitrogenous air pollutants were monitored along an elevation gradient in the Class I San Gorgonio Wilderness area (San Bernardino Mountains, California, U.S.) during the summer of 2000 (mid-June to mid-October). Passive samplers were exposed for 2-week periods at six sampling sites located at 300 m intervals ranging from 1200 to 2700 m elevation. Elevated concentrations of ozone were found in this area with summer 24-h hourly means ranging from 53 to 59 ppb. The highest ozone concentrations were detected in the period July 25-August 8, reaching values of 64 to 72 ppb expressed as 2-week mean. Passive-sampler ozone data did not show a clear relationship with elevation, although during the periods with higher ozone levels, ozone concentrations were higher at those sites below 2000 m than at sites located above that elevation. All nitrogenous pollutants studied showed a consistent decrease of concentrations with elevation. Nitrogen dioxide (NO2) levels were low, decreasing with increasing elevation from 6.4 to 1.5 ppb summer means. Nitric oxide (NO) concentrations were around 1 to 2 ppb, which is within the range of the detection levels of the devices used. Nitric acid (HNO3) vapor concentrations were lower at higher elevations (summer means 1.9-2.5 microg m(-3) than at lower elevations (summer means 4.3-5.1 microg m(-3). Summer concentrations of ammonia (NH3) were slightly higher than nitric acid ranging from 6 microg m(-3) at the lowest site to 2.5 microg m(-3) registered at the highest elevation. Since complex interactions between ozone and nitrogenous air pollutants have already been described for forests, simultaneous information about the distribution of these pollutants is needed. This is particularly important in mountain terrain where no reliable models of air pollutant distribution exist.

Air Pollutants↗

Neuroanatomical distribution of Huntingtin-associated protein 1-mRNA in the male mouse brain.

Huntingtin-associated protein 1 (HAP1) was identified as an interactor of the gene product (Huntingtin) responsible for Huntington's disease and found to be a core component of the stigmoid body. Even though HAP1 is highly expressed in the brain, detailed information on HAP1 distribution has not been fully described. Focusing on the neuroanatomical analysis of HAP1-mRNA expression using in situ hybridization histochemistry, the present study clarified its detailed regional distribution in the entire mouse brain. Mouse HAP1 (Hap1)-mRNAs were abundantly expressed in the limbic-related forebrain regions and midline/periventricular brainstem regions including the olfactory bulb, limbic-associated cortices, hippocampus, septum, amygdala, bed nucleus of the stria terminalis, preoptico-hypothalamic regions, central gray, raphe nuclei, locus coeruleus, parabrachial nuclei, nucleus of the solitary tract, and area postrema. In contrast, little expression was detected in the striatum and thalamus, implying that Hap1 is associated with neurodegeneration-sparing regions rather than target lesions in Huntington's disease. The distribution pattern, resembling that of the stigmoid body, suggests that HAP1 and the stigmoid body are implicated in protection from neuronal death rather than induction of neurodegeneration in Huntington's disease, and that they play an important role in integrating instinct behaviors and underlying autonomic, visceral, arousal, drive, memory, and neuroendocrinergic functions, particularly during extensive homeostatic or emotional processes. These data will provide an important morphological base for a future understanding of functions of HAP1 and the stigmoid body in the brain.

Animals↗

Electron localization function as information measure.

The conditional two-electron probability function, which defines the electron localization function (ELF) of Becke and Edgecombe in the Kohn-Sham theory, is interpreted as the nonadditive (interorbital) Fisher information contained in the electron distribution. The probability normalization considerations suggest a use of the related information measure defined in terms of the unity-normalized probability distributions (shape factors of the electron densities), as the key ingredient of the modified information-theoretic ELF. This modified Fisher information density is validated by a comparison with the original two-electron probability function. Illustrative applications to typical molecular systems demonstrate the adequacy of the modified information-theoretic ELF in extracting the key features of the electron distributions in molecules. The overall Fisher information itself and the associated information-distance quantities are also proposed as complementary localization functions.

Journal Article↗

Distribution and correlates of high-density lipoprotein subclasses among children and adolescents.

Levels of high-density lipoprotein (HDL) cholesterol among children vary by sex and race/ethnicity and are correlated with age, obesity, and other characteristics. Several studies of adults have indicated that atherogenicity of HDL particles may vary by size, but there is little information on the distribution and correlates of HDL subfractions in early life. We used nuclear magnetic resonance (NMR) spectroscopy to determine the mean HDL particle size and levels of 3 HDL subclasses among 10- to 17-year-olds (n = 918). We found the mean HDL particle size to be (1) inversely associated with age among boys, (2) larger among girls than boys, and (3) larger among black children than among white children. These associations with particle size reflected contrasting associations with various HDL subclasses; among boys, for example, levels of large HDL decreased with age, whereas levels of small HDL remained constant (black boys) or tended to increase (white boys). Furthermore, relative weight and levels of both triglycerides and low-density lipoprotein (LDL) cholesterol were associated inversely with levels of large HDL, but positively with levels of small HDL. These contrasting associations suggest that the role of HDLC in coronary heart disease (CHD) may be more complex than previously thought, and that the analysis of HDL subclasses may improve the accuracy of CHD prediction.

Adolescent↗

Investigating 3D tumor distribution for optimized diagnosis of prostate cancer.

Transrectal Ultrasonography (TRUS) based systematic needle biopsy of the prostate has been widely used clinically in the diagnosis of prostate carcinoma. Current protocols for prostate biopsy, such as the Sextant Protocol, however, have been proven to be insufficient in cancer detection since these protocols were built without having accurate information on 3D distribution of prostate cancers. In this research, our goal is to optimize prostate biopsy protocols by statistically investigating spatial distributions of prostate cancers. Based on the low-resolution nature of ultrasound imaging and the current clinical conventions, we propose to divide each individual prostate gland into different zones that are can be recognized and accessed by the urologists with ultrasound images during biopsy. By calculating cancer appearance inside each of these zones using a large number of prostate samples, we get the overall distributions of prostate cancers based on which an optimal biopsy protocol can be developed.

Biopsy, Needle↗

Distribution of injected MRI contrast agents in mouse livers studied by confocal and SIMS microscopy.

OBJECTIVE: To localize magnetic resonance imaging (MRI) contrast agents injected intravenously into mouse livers. STUDY DESIGN: Parallel studies were performed on fluorescent europium and nonfluorescent, paramagnetic gadolinium and on a product combining nanoparticles of Fe and Texas Red to obtain combined information on the distribution of these molecules inside the liver. The distribution of different superparamagnetic iron oxides was also studied because the size of these new compounds is not always convenientfor microcirculation studies. RESULTS: Europium and Texas Red can be detected by confocal microscopy. Europium, iron and gadolinium can be detected by secondary ion mass spectrometry (SIMS) microscopy. Studies confirmed the complementarity of both microscopies. They also confirmed the possibility of using europium as a model of gadolinium to analyze thefate of MRI contrast agents. CONCLUSION: The methodology can be used on mice injected intravenously and analyzed by confocal and SIMS microscopy to localize MRI contrast agents inside cellular and tissue specimens of mice.

Animals↗

A statistical analysis of prescreening alarms in a population of normal and abnormal gynecologic specimens.

A multidimensional slit-scan flow system has been developed to serve as an automated prescreening instrument for gynecological cytology. Specimens are classified abnormal based on the number of cells having elevated nuclear fluorescence (alarms). An alarm region in a bivariate histogram of nuclear fluorescence versus nuclear-to-cell-diameter ratio is defined. Alarm region probability arrays are calculated to estimate the probability that an alarm falling in a particular bin of the alarm region is either from a normal or an abnormal specimen. From these arrays, a weighted alarm index is generated. In addition, summary indices are derived that measure how the distribution of alarms in each specimen compares with the average distributions for the normal and abnormal specimen populations. These indices together with current features are evaluated with respect to their utility in specimen classification using a nonparametric classification technique known as recursive partitioning. Resulting classification trees are presented that suggest information in the distribution of alarms in the bivariate histogram. In addition, they validate the features and rules currently used for specimen classification. Recursive partitioning appears to be useful for multivariate classification and is seen as a promising technique for other applications.

Cytodiagnosis↗

Syndromic surveillance using minimum transfer of identifiable data: the example of the National Bioterrorism Syndromic Surveillance Demonstration Program.

Several health plans and other organizations are collaborating with the Centers for Disease Control and Prevention to develop a syndromic surveillance system with national coverage that includes more than 20 million people. A principal design feature of this system is reliance on daily reporting of counts of individuals with syndromes of interest in specified geographic regions rather than reporting of individual encounter-level information. On request from public health agencies, health plans and telephone triage services provide additional information regarding individuals who are part of apparent clusters of illness. This reporting framework has several advantages, including less sharing of protected health information, less risk that confidential information will be distributed inappropriately, the prospect of better public acceptance, greater acceptance by health plans, and less effort and cost for both health plans and public health agencies. If successful, this system will allow any organization with appropriate data to contribute vital information to public health syndromic surveillance systems while preserving individuals' privacy to the greatest extent possible.

Bioterrorism↗